Source: MICHIGAN STATE UNIV submitted to NRP
PLANT PRODUCTS AS FUNCTIONAL FOODS AND BOTANICAL MEDICINES TO IMPROVE HUMAN, ANIMAL AND PLANT HEALTH
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
0157691
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
May 1, 2012
Project End Date
Apr 30, 2017
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
MICHIGAN STATE UNIV
(N/A)
EAST LANSING,MI 48824
Performing Department
Horticulture
Non Technical Summary
Compounds derived from plants provide a rich source of biological activity that can improve human, animal and plant health. These natural products include pharmaceuticals, phytoceuticals, agrochemicals and animal health products. Recently, intense interest has been generated by research suggesting that phytochemicals in the diet can combat chronic diseases such as cancer, inflammation, diabetes and cardiovascular diseases. Nutraceuticals or dietary supplements enriched in beneficial phytochemicals or in purer forms are being developed by industry as functional foods and phytomedicines. The study of bioactive natural products, therefore, leads to a fuller understanding of biological systems related to human health, and to the discovery of compounds with beneficial properties that can be exploited commercially. The proposed project will discover biologically active natural products from generally regarded as safe (GRAS) plants, fruits, vegetables and other horticultural and agricultural crops. We will also determine the mode of action(s) of these bioactive constituents in order to process the respective plant material as products for agricultural, pharmaceutical and nutraceutical applications. This research should yield value-added products and provide additional income to the growers in Michigan and USA. Also, based on the potential of nutraceuticals or botanical drug applications, new crops can be introduced to fill the need for nutraceuticals and botanical drug industries. The results from this research should give a leading edge to agrochemical, food and pharmaceutical industries in Michigan and USA. This project also fits to the overall mission of Michigan State University AgBioResearch to be a leader in food and health, bio-economy and sustainable ecosystems initiatives and programs. Over the last five years, We have isolated and characterized several natural products with biological activities that are relevant to improving quality of health. Some of the compounds are anthocyanins in fruits and vegetables with antiobese and blood sugar regulating activities. Also, a variety of compounds have been isolated from several plants that are being consumed as supplements or as traditional medicines. Some of these compounds are currently under investigation for their mode of action in order to develop as phytomedicines or therapeutic agents for alleviating or treating illnesses such as type-2 diabetes, Alzheimers disease, inflammation and cancer. Natural therapeutics, LLC has licensed several of these technologies and plan to start clinical trials on anthocyanin to treat type-2 diabetes, Withanamides to treat Alzheimers disease and withanolides to treat inflammation. My laboratory will be closely working with Natural Therapeutics on all aspects of clinical trials. We will continue to investigate GRAS plants, non-traditional fruits and vegetables and edible mushrooms for functional food properties using our established bioassays, chromatographic, spectral and chemical protocols. The expected outcome will be novel health-beneficial products from these agricultural raw materials.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
7012410100050%
7012410101030%
7012410112020%
Knowledge Area
701 - Nutrient Composition of Food;

Subject Of Investigation
2410 - Cross-commodity research--multiple crops;

Field Of Science
1120 - Nematology; 1010 - Nutrition and metabolism; 1000 - Biochemistry and biophysics;
Goals / Objectives
The Bioactive Natural Products and Phytoceuticals laboratory at Michigan State University is engaged in the discovery, isolation and identification of phytoceuticals and, in conjunction with scientists at Michigan State University and elsewhere to defining the balance between their benefits and risks. Our research involves bioassay directed discovery, purification and chemical characterization of natural products from generally regarded as safe (GRAS) plants using in vitro anticancer, antioxidant, anti-diabetic, anti-inflammatory, antifungal, antibacterial, nematicidal, mosquitocidal, antipasrasitic and insecticidal assays for human health, animal health, plant health and crop enhancement. Our research focuses on developing mechanism-based natural products for prevention and treatment of human illnesses. These include diabetes, cardiovascular diseases, inflammation, cancer, musculoskeletal and neurological diseases and illnesses caused by parasites and microbes. We use commonly consumed plants including spices, fruits and vegetables as the source to probe and develop phytoceuticals with health benefits. Some of the specific objectives are (1) study GRAS plants for enhanced production of bioactive anthocyanins and establish factors affecting the elevated biosynthesis of anthocyanins, (2) isolate and purify anthocyanins for in vitro and in vivo studies, (3) identify which of these anthocyanins and its dose is sufficient for modulating hepatic lipid storage/synthesis and insulin secretion/biosynthesis in obese mouse models, (4) characterize metabolic and gene expression changes induced by anthocyanin(s) in vivo, (5) examine potential mechanisms for anthocyanin(s) affects in vitro , (6) contiune to investigate GRAS plants for novel natural products that are biologically active and (7) study chemistry and mechanism of action of anticancer and antiinflamamtory agents in edible mushrooms.
Project Methods
Bioassay-guided preparation of plant extracts and pure bioactive compounds: Fresh plant material will be extracted with water followed by methanol. All extracts will be assayed for various bioactivities. The extracts that show activity in any one of those preliminary assays will then be subjected to bioassay-directed fractionation and purification according to protocols established in Nairs laboratory. Separation and isolation of active compounds will be achieved by partition chromatography, silica or C-18 VLC or medium pressure liquid chromatography (MPLC). For final purification, we will use recycling preparative HPLC. The active fractions will be purified using bioassay-guided fractionation to obtain pure bioactive components. Numerous bioassays will be used and some are described below. Antiinflammatory assays will be conducted using Cyclooxygenase enzymes (COX-1 and COX-2. The formation of prostaglandins from arachidonic acid by prostaglandin synthase is a well-studied process and the effects of the prostaglandins can result in the stimulation of inflammation and associated pain. COX-I enzyme inhibitory assay will be conducted with an enzyme preparation from ram seminal vesicles . COX-2 activity will be determined using a preparation from insect cell lysate and diluting with Tris buffer to give an approximate final concentration of 1.5 mg protein/mL. The initial rate of O2 consumption using an Instech micro oxygen chamber and electrode attached to an YSI model 5300 biological oxygen monitor. Anti-Oxidant Assay Antioxidant bioassays will be conducted by analysis of model liposome oxidation using fluorescence spectroscopy. The lipid, 1-stearoyl-2-linoleoyl-sn-glycerol-3-phosphocholine and fluorescent probe, 3-[p-(6-phenyl)-1,3,5-hexatrienyl]-phenylpropionic acid, will be combined in DMF and dried in vacuo at RT. Anticancer Assays Incubation of AGS and other tumor cell lines selected for the study with malvidin, harvest cells, collect cell-free medium and assay lyophilized cell-free medium containing the metabolites for tumor cell proliferation inhibitory activity. MCF-1 (Breast cancer), SF-268 (CNS) and NCI-H460 (Lung cancer) cultures were purchased from the National Cancer Institute (Bethesda, MD). HCT-116 (Colon cancer) and AGS (Stomach cancer) cultures were purchased from the American Type Culture Collection (Rockville, MD). All cell cultures are maintained in Nairs laboratory, the Bioactive Natural Products and Phytoceuticals (BNPP) at MSU.

Progress 05/01/12 to 04/30/17

Outputs
Target Audience:Target audience during the life of this project comprised of high school, under graduate and graduate students, visiting professors from around the world, postdoctoral fellows, growers and industry personel. Numerous visiting professors and postdoctral fellows from countries such as Egypt, Turkey, India, Iraq, Philippines, Saudi Arabia, Sri Lanka, China, Brazil, Kenya, Tanzania, Senegal andJamaica directly benefited from the project objectives, in addition to scientists and professionals from USA. The project resulted in a number of peer reviewed high-impact journal publications. Most of these publications are highly cited by peers around the world. Some of the research outcomes are in the process of materializing as commercial products, for example to treat Alzheimer's disease. Therefore, our functional food theme and outcomes have impacted the quality of life of citizens in the USA and arndthe world. Ouocmes from this research still has the potential to improv te health benefits of citizens in the USA and world. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Trained manyvisiting professors and post-doctoral fellows from USA, Egypt, Turkey, India, Iraq, Philippines, Saudi Arabia, Sri Lanka, China, Brazil, Kenya, Tanzania, Senegal, and Jamaica. In additoin, several graduate students, undergraduate students and some high school students were trained and benefited from our project obejctives in planningtheir future studies and careers. How have the results been disseminated to communities of interest?Our project resulted in numerous peer-reviewed high impact journal publicatoins. Most of these publicatrions are highly cited by our peers around the world. We also presented research results from this project in several nationaland international sceintific gatherings. Also, several seminars and talks were attended by non-sceintists and memebrs of sceintific communities other than our area of expertise. On a number of occasions, our research results from this project were covered by television, radio, magazines ad news media in the nation and around the world. What do you plan to do during the next reporting period to accomplish the goals?We will continue the functional foood research and explore additional plants for new products to improve health and quality of life of our citizens.

Impacts
What was accomplished under these goals? Our anthocyanin research resulted in better understandig of itshalth benefts including fruits, vegetables and rice that contain this bioactive phenolic compounds. General public is now aware of the health benefits of these phenolics in frutis and vegetables. It also helped fruit and vegetable growers to add value to their produce, in additoin to the food processing industries. Our research on functional foodsor foods containingbioactive natural compounds that providehealth benefits significanlty benefited growers, industry andconsumers alike. Our research outcomes have contributed to the mission of food and health and healthy living. Television, radio, magazine and newspaper coverage of our reserach outcomes helped lay people to assimilate it and helped them to include frutits and vegetables that contain bioactive helath benefical compounds in their daily diet. Hopefully, this will lead to a decreasein obesity, type-2 diabetes ansd other chronic diseases that can be prevented from healthy diet and living.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: C. Zhang, W. A. Khan, J. Bakht and M. G. Nair. New antiinflammatory sucrose esters in the natural sticky coating of tomatillo (Physalis philadelphica), an important culinary fruit. Food Chemistry. 196, 726-732, 2016.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: R.G. Reyes and M. G. Nair. Lignolytic and leaf litter degrading mushrooms from the Philippines with antioxidant activities. International journal of Pharmaceutical Research and Allied Sciences. 5, 67-74, 2016.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: A. A. Dissanayake, C. M. Wagner and M. G. Nair. Chemical Characterization of Lipophilic Constituents in the Skin of Migratory Adult Sea Lamprey from the Great Lakes Region. PLOS ONE | DOI:10.1371/journal.pone.0168609 December 19, 2016.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: J. A. Mmongoyo, M. G. Nair, J. E. Linz, F. Wu, A. Dissanayake, C. Zhang, J. K. Mugula and G. M. Strasburg. Bioactive compounds in Diospyros mafiensis roots inhibit growth, sporulation and aflatoxin production by Aspergillus flavus and Aspergillus parasiticus. World Mycotoxin Journal. In Print. DOI 10.3920/WMJ2016,2017.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: J. A. Mmongoyo, F. Wu, J. E. Linz, M. G. Nair, J. K. Mugula and G. M. Strasburg. Aflatoxin levels in sunflower seeds and cakes collected from micro- and small-scale sunflower oil processors in Tanzania. PLOS ONE. https://doi.org/10.1371/journal.pone.0175801, April 18, 2017.


Progress 10/01/15 to 09/30/16

Outputs
Target Audience:Our target auduience is comprised of health professionals, food producers, food industry, students, researchers and general public. The research we conducton botanicals, spices, and genrally regarded as safe plants (GRAS) used in traditional medicine has been cited by researchers around the world,as eveidenced by citation index of our research publications. Our research publications have also been read by public in genral beacuse of its impact to people'shealth and wellness. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?A visting Ph.D. studfent from Peshawar Agricultural University of Pakistan participated in the research on tomatillio sucrose esters. This student learned basic principles in natural products chemistry, chromatographic purification,structure elucidation of natural products by spectroscopy and in vitro bioassays. A professor from Western Michigan University participated in the Lake Huraon tansy project. he learned techniques in extraction, chromatographic purification and structure elucidation of natural products by spectroscopic methods. Also, two postdoctoral fellows were primary researchers on these two projects. Publications from these research projects contributed to theprofessional development of all involved. How have the results been disseminated to communities of interest?Our published research results are available to research communities including students and professionals. Talks given to gneral audiences are as follows: 1)Moving Technology from Laboratory-Personal experiences of failure and successes. USPTO National Teachers Summer Institute-3, Michigan State University, East Lansing, Michigan, July 19, 2016, 2)Natural Products Research: Opportunities and Challenges. Qassim University, Qassim, Saudi Arabia, February 14, 2016, 3)Health-benefits and Sugar Quantification in Commercial Saudi Arabian Date fruits. Qassim University, Saudi Arabia, February 14, 2016 and4)Withanamides in Aswagandha botanical to treat and prevent Alzheimer's disease. Invited Speaker, Division of Agricultural and Food Chemistry: Bioactives 7 Neurodegenerative Diseases. 251st American Chemical Society National meeting & Exposition, San Diego, California, March 13, 2016. What do you plan to do during the next reporting period to accomplish the goals?We have a number of ongoing projects in the area of bioactive natural products. We continue to evaluate generlaly regarded as safe plants for their potential use in ameliorating human, animal and plant diseases. In adidtion, we have a funded project by Great lakes Fisheries Commisiion to identify alarm cue molecules in sea lamprey, a fish parasite. Also included in the plan will be sumitting manuscripts for publications, presentations of our research findings in national and international venues, professionalservices such as reviewing manucripts for peer-reviwed international journals, review grant applications for national and international funding agencies, human capacity building in research and development in developing countries

Impacts
What was accomplished under these goals? Tomatillo,a popular culinary fruit, is coated with asticky material andhas never been investigated. We chemcially characterized the compositionof this sticky material and identified it assucrose estersby spectroscopic methods. The solvent extract of the sticky material from the whole fresh fruit and pure sucrose estersshowed antiinflammatory activity as confirmed by in vitro cyclooxygenase enzymes (COX-1 and -2) inhibitory assays. The COX enzyme inhibitory activity of extract and isolates wassimilar to non-steroidal antiinflammatory drugs (NSAIDs) aspirin, ibuprofen and naproxen, used as positive controls. Tanacetum huronense (Lake Huron tansy)is native to the upper Midwest region of USA and Canada and used in traditional medicine. Weexamined for the presence of anticancer compounds, based on anecdtoal reports, using an in vitro human tumor cell proliferation inhibition assay, with glioblastoma derived cell line U-87 MG. Bioassay-directed purification of the ethyl acetate extract of the aerial portion of this plant identified six active sesquiterpenoid lactones. Among these, two compounds identifiedwere new structural analogs. One of the most abundant isolates, tanacin, exhibited the greatest inhibition of human glioblastoma with an IC50 value of 4.5 μg/mL.

Publications

  • Type: Journal Articles Status: Published Year Published: 2016 Citation: C. Zhang, W. A. Khan, J. Bakht and M. G. Nair. New antiinflammatory sucrose esters in the natural sticky coating of tomatillo (Physalis philadelphica), an important culinary fruit. Food Chemistry. 196, 726-732, 2016.
  • Type: Journal Articles Status: Published Year Published: 2016 Citation: A. A. Dissanayake, B. E. Bejcek, C. Zhang and M.G. Nair. Sesquiterpenoid Lactones in Tanacetum huronense Inhibit Human Glioblastoma Cell Proliferation. Natural Product Communications. 11, 579-582, 2016.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2016 Citation: Q. Li, C. Zhang, A. A. Dissanayake, Q. Gao and M. G. Nair. Chinese Yam, a popular starchy food, exhibited antiinflammatory activity as shown by cyclooxygenase enzyme inhibition. Natural Product Communications.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2016 Citation: C. Zhang, S. A. Aldosari, P.S.P.V. Vidyasagar, P. Shukla and M. G. Nair. Health-benefits of date fruits produced in Saudi Arabia based on in vitro antioxidant, antiinflammatory and human tumor cell proliferation inhibitory assays. Journal of the Saudi Society of Agricultural Sciences. In press.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: J. Mmongoyo, F. Wu, J. E. Linz, M. G. Nair, J. K. Mugula and G. Strasburg. Aflatoxin levels in sunflower seeds and cakes collected from micro- and small-scale sunflower oil processors in Tanzania. Institute of Food technologists (IFT), Chicago, Illinois, July16-19, 2016. ID. 15078, TRP16.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2016 Citation: M. G. Nair. Withanamides in Aswagandha botanical to treat and prevent Alzheimers disease. American Chemical Society National Meeting, San Diego, California, March 13-17, 2016. ID. 2364645-AGFD 5.


Progress 10/01/14 to 09/30/15

Outputs
Target Audience:Our target auduience is comprised of health professionals, food producers, food industry, students, researchers and general public. The research on Withania somnifera, a botanical, licensed by a Michigan startup company, is being considered for human clinical trials in the treatment and prevention of Alzheimer's disease. Our publicatoin on fenugreek spice in Food Chemistry has been read or downloaded by more than 1114 since its publication in January 2015 (data by Article Usage Alert by Science Direct). Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?One full-time and a part-time postdoctoral fellows were involved in the research reported during htis period. Dr. Bruce Bejeck, a sabbatical professor from Western Michigan University, Kalamazoo, Michigan were also a memebr of the bioassay-directed isoation and characterization of compounds. Visiting professors from University of Alexandria, Egypt and King Saud University, Riyadh, saudi Arabia were trianed in bioacive naturalproducts chemistry during this reportins period. In addition, Ph.D. students from China and Tanzania are being trained and continuing their thesis projects in the laboratory. Trined several graduate and undergraduate students in analytical and bioassay methods. How have the results been disseminated to communities of interest?Publications, presentations, email and telephone communications and public talks. In addition to publication list, the presntations were as follows: Mitigation of Alzheimer's disease using Withania somnifera compounds withanamides. Senior Citizens Forum, Hannah Community Center, East Lansing, Michigan. April 22, 2015. Medicines from nature to treat human diseases. Kerala University of Fisheries and Ocean Studies (KUFOS), Panangad, Kochi, Kerala, India. April 13, 2015. Strategic planning for human and research capacity strengthening at ICAR Directorate of Medicinal and Aromatic Plants, Anand, Gujarat, India. April 7-8, 2015. Strategy to develop natural medicines from medicinal and aromatic plants. ICAR Directorate of Medicinal and Aromatic Plants (DMAP), Anand, Gujarat, India. April 7, 2015. Bioassay-directed isolation and characterization of a sea lamprey deterrent. Great Lakes Fisheries Commission, Ann Arbor, Michigan. March 5, 2015. What do you plan to do during the next reporting period to accomplish the goals?We have a number of ongoing projects in the area of bioactive natural products from agricultural crops and botanicals. We continue to evaluate generlaly regarded as safe plants for their potential use in ameliorating human, animal and plant diseases. In adidtion, we plan to submit research proposals to NIH, USDA and other agencies for funding of our research. Sumitting manuscripts for publications, presentations of our research findings in national and international venues, professiona lservices such as reviewing manucripts for peer-reviwed international journals, review grant applications for national and international funding agencies, human capacity building in research and development in developing countries and continue to serve as a resource person in bioactive natural products.

Impacts
What was accomplished under these goals? We have established the efficacy, toxicity and blood brain barrier permeability of bioactive ingredeints in Withania somnifra fruit as a botanical drug to treat and prevent Alzheimer's disease. This technology, licensed by a Michigan company, is being evaluated to determine clinical efficacy in AD pateints. We determined the functional food qulaity of fenugreek spice and reported its bioactive constituents with antiinflammatory, antioxidant and tumor cell proliferation inhibitory activities. This research article, published in the journal Food Chemistry, has already been read or downloaded by more than 1114 times as indicated the usage data by Science Direct. Similarly, we also determined the functional food qulaity of honey locust flowers used in food and traditional medicine. This reaserch was for the first time and compounds reported from it showed antioxidant and antiinflammatory activities similar to aspirin, ibuprofen and naproxen. Nutmeg is another popular spice. The agricultural waste from nutmeg production has never been investigated for its value-added use. Our research on nutmeg pericarp, normally discarded in landfills, showed its potential use as a functional food. It contianed similar compounds present in the nut, nutmeg, and hence shall be processed as a food ingredient. There are numerous varities of commercial date fruits in the market. For the first time, we profiled and characterized the sugar content in 30 major marketed varieites of date fruits. In another research, we established leaf constituents of Curcuma spp (its rhizome is highly valued spice) suppress plant pathogenic nematode and increse the population of beneficial bacterial-feeding nematodes. In another study, a formulation containing soap, plant extract and hot pepper extracts controlled white flies and corn earworm infestation, major plant pests affect vegetable and corn production around the world.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: C. Zhang, A. Dissanayake, K. Kevsero?lu and M. G. Nair. Evaluation of coriander spice as a functional food by using in vitro bioassays. Food Chemistry. 167, 24-29, 2015.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: M. G. Nair, N. Seenivasan, Y. Liu, R.M. Feick, Z-T-Z. Maung and H. Melakeberhan. Leaf constituents of Curcuma spp. suppress Meloidogyne hapla and increase bacterial-feeding nematodes. Nematology. 17, 353-361, 2015.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: C. Zhang, S. A. Aldosari, P.S.P. V. Vidyasagar, P. Shukla and M. G. Nair. Determination of the variability of sugars in date fruit varieties by HPLC. Journal of Plantation Crops. 43, 53-61, 2015.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: C. Zhang, E. Jayasree, P. Suresh Kumar and M. G. Nair. Antioxidant and antiinflammatory compounds in nutmeg (Myristica fragrans) pericarp as determined by in vitro assays. Natural Product Communications. 10 (8), 1399-1402, 2015.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: G. Kambou and M. G. Nair. Citec soap: A new additive for Cassia nigricans and Capsicum annum aqueous extracts to control white flies (Bemisia tabaci, Homoptera, Aleyrodidae) and Helicoverpa armigera (Lepidoptera, Noctuidae) on tomato in Burkina Faso. International Journal of Agricultural Innovations and Research. 3, 1807-1813, 2015.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: C. Zhang, A. Dissanayake and M. G. Nair. Functional food property of honey locust (Gleditsia triacanthos) flowers. Journal of Functional Foods. 18, 266-274, 2015.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2015 Citation: G. Kambou and M. G. Nair. The citec soap, a new additive for cassia nigricans, capsicum annum aqueous extracts used against white flies (bemisia tabaci (homoptera: aleyrodidae) and helicoverpa armigera (lepidoptera: noctuidae) on tomatoes, in Burkina Faso. XVIII International Plant Protection Congress, Berlin, Germany, August 24-27, 2015.


Progress 10/01/13 to 09/30/14

Outputs
Target Audience: Our research on Withania somnifera (Aswagandha), a popular botanical consumed for medicinal value, continues. Thi sreporting period we confirmed that the active ingredients in W. somnifera fruits, withanamides, passed the blood brain barrier in mouse models. We have reported earlier that withanamides inhibit the action of beta amyloid, a causative agent for Alzheimer's disease. This resuslt has genrated considerable interst among medical professionals as well as caregivers. Our ongoing research on bioactive plant products continues t otarget gowers, industrial partners and consumers. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Two full-time postdoctoral fellows are involved in this reasearch. Prof. Bruce bejeck, a sabbatical professor from Western Michigan University, Kalamazoo, Michigan is being trained in the bioassay-directed isolation, purification and characterization of bioactive compounds. In addition, two visting professors (Iraq), three Ph.D. students from Brasil, New Zealand and Pakistan received training in bioactive natural products. These students completed research projects to complete their Ph.D. thesis. We also have helped and trained other graduate and undergraduate students at MSU. How have the results been disseminated to communities of interest? Publications, presentations, email communications, telephone conversations and public talks. What do you plan to do during the next reporting period to accomplish the goals? We have a number of ongoing projects on bioactive natural products from agricultural crops, botanicals, fruits and vegetables. We continue to evaluate them for their potential use in ameliorating human, animal and plant diseases. We also continue to write research proposals to NIH, USDA and other agencies for funding. Submitting manuscripts for publications and presenttions on our research findings in national and international venues will continue.

Impacts
What was accomplished under these goals? Withania somnifera, a botanical, has been used for medicinal use around the owrls. We have published extensively on its bioactive ingredients and potential use of its extract for treatment and prevention of Alzheimer's disease (AD) based on in vitro protection of neuronal cells by the inhibition of beta amyloids. One of the improtant criterions of an AD drug is its ability to pass blood brain barrier (BBB). Our published work in mouse models confirmed that withanamides, the inhibitors beta amyloid protein, passed the bllod brain barrier. Michigan State University holds patents on the technology and licesnsed it to a Michigan Company. This promisign finding has helped the Michigan company to solicit funds in order to commercialize the technology. We also continue to work on other agricultural crops for their use as functional foods. That is, foods that serve medicinal value in addition to nutrition.

Publications

  • Type: Conference Papers and Presentations Status: Published Year Published: 2014 Citation: S. K. Vareed, A. K. Bauer, K. M. Nair, Y. Liu, B. Jayaprakasam and M. G. Nair. Blood brain barrier permeability of bioactive withanamides present in Withania somnifera fruit extract. Phytotherapy Research. 28, 1260-11264, 2014. C. Zhang, S. A. Aldosari, P.S.P.V. Vidyasagar, P. Shukla and M. G. Nair. Antioxidant, antiinflammatory and antitumor activities of 29 varieties of date fruits. American Society of Pharmacognosy 2014 Annual Meeting, August 2-6, 2014, Oxford Mississippi, Abstract 0398-000453, Planta Med 2014; 80 - PE11. C. Zhang, S. A. Aldosari, P.S.P.V. Vidyasagar, P. Shukla and M. G. Nair. Quantification of sugars in date fruits from 29 date palm varieties. American Society of Pharmacognosy 2014 Annual Meeting, August 2-6, 2014, Oxford Mississippi, Abstract 0398-000447, Planta Med 2014; 80 - PPL25. C. Zhang, A. A. Dissanayake and M. G. Nair. Honey locust (Gleditsia triacanthos) flowers and its bioactive constituents. American Society of Pharmacognosy 2014 Annual Meeting, August 2-6, 2014, Oxford Mississippi, Abstract 0398-000439, Planta Med 2014; 80 - PD120. P. Shukla, S. A. Aldosari and M. G. Nair. Pulicaria undulata, an arid plant, afforded extracts with potential to manage red palm weevil Rhynchophorus ferrugineus Oliv. Entomological Society of North America 2014 Annual meeting, Portland, Oregon, November 16-19.


Progress 01/01/13 to 09/30/13

Outputs
Target Audience: The overall goal of this project is to discover health beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants consumed around the world as a dietary ingredient or as an ingredient in traditional medicines.Our research continues to provide scientific basis and support to anecdotal health claims associated with a number of traditional foods and botanical supplements available to consumers. Our target audiences are scientists and consumers around the world. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Postdoctoral fellow, undergraduate students, international visiting sceintists were involved in these projects. All were trained on variious skills in the area of bioassays, extraction of plant materials, chromatographic purification of active compounds and spectroscopic analysis and interpretation of results. Some of them were also exposed to manuscript writing and data compiling and interpretation. How have the results been disseminated to communities of interest? Peer-reviewed journal article publications. Presentations in meetings and discussions. What do you plan to do during the next reporting period to accomplish the goals? We continue to research on plants that are generally regardes as safe (GRAS), fruits, spices and vegetables in order to determine their health beneficial effects and isolate and characterize value-added natural products present in it to develop as potential products for human, animal and plant helath.

Impacts
What was accomplished under these goals? We studied Ajwa date fruits for its health benefits. We determined percentages of seed, moisture, fructose, glucose, soluble protein and fiber in Ajwa dates as 13.24, 6.21, 39.06, 26.35, 1.33 and 11.01, respectively. The water and organic extracts of Ajwa dates showed significant antioxidant and antiinflammatory activities as demonstrated by their lipid peroxidation and cyclooxygenase enzymes inhibitions in in vitro analyses. Bioactivity-guided purifications afforded seven compounds, in addition to phthalates and fatty acids. Among theses, three compounds showed significant antioxidant and antiinflammatory activities in vitro. The water soluble portion of the fruit contained priamarily fructose and glucose along with soluble proteins. The protein fraction also showed high antioxidant and antiinflammatory activity. It is imprtant to note that date fruits contianed only fructose (66%) and glucose (34%). Lack of sucrose and reduced glucose content contribute to overall health benefit. We also characterized and determined biological activity of flavonoids in ripe fruit of an anthracnose-resistant blueberry cultivar and correlated the phenolic content to its resistance to pathogens. Another project was on functional food quality of Curcuma caesia, Curcuma zedoaria and Curcuma aeruginosa endemic to northeastern India and our research established the chemical basis for its anecdotal health claims. These Curcuma spp. may provide added income to the growers due to its health benefits. A popular landscape plant Berberis thunbergii var. atropurpurea was investigated for value-added antioxidant and antiinflammatory constituents and found that it contians primarily berberine, a product already popular in the supplement market.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: C. Zhang, R. E. Schutzki, M.G. Nair. Antioxidant and antiinflammatory compounds in the popular landscape plant Berberis thunbergii var. atropurpurea. Natural Product communications. 8, 165-168, 2013. Y. Liu, S.S. Roy, R.H.C. Nebie, Y. Zhang and M.G. Nair. Functional food quality of Curcuma caesia, Curcuma zedoaria and Curcuma aeruginosa endemic to northeastern India. Plant Foods for Human Nutrition. 68, 72-77, 2013. T.D. Miles, C. Vandervoort, M.G. Nair and A.C. Schilder. Characterization and biological activity of flavonoids from ripe fruit of an anthracnose-resistant blueberry cultivar. Physiological and Molecular Plant Pathology, 83, 8-16, 2013. C. Zhang, S. A. Aldosari, P.S.P. Vidyasagar, K. M. Nair and M. G. Nair. Chemistry of Ajwa date fruit and its health-benefits as indicated by antioxidant and anti-inflammatory activities. J. Agric. Food Chemistry. 61, 5834-5840, 2013.


Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: The overall goal of this project is to discover health beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants consumed around the world as a dietary ingredient or as an ingredient in traditional medicines. In this report I summarize the results from our research on the metabolomics on Withania somnifera, a herb used in traditional medicine and as an ingredient in dietary supplements; bioactive compounds in Prosopis cineraria, the pods of a tree grown in the desert and eaten as a vegetable; lipid peroxidation and cyclooxygenase enzymes inhibitory compounds in fenugreek spice, ginger, Curcuma longa, Curcuma mangga; health-beneficial properties of Jamaican Psidium cattleianum (strawberry guava) and Psidium guajava (common guava) fruits; and synergistic inhibition of interleukin-6 production in adipose stem cells by tart cherry anthocyanins and atorvastatin. Anthocyanins present in vegetables and fruits are health-beneficial. We continued our investigation of anthocyanin further for its helth-beneficial effects. Studies have shown positive correlations between inflammatory cytokines such as interleukin-6 (IL-6) and the development of chronic diseases including cardiovascular disease by activating C-reactive protein (CRP). Atorvastatin calcium (lipitor) and anthocyanins in tart cherry demonstrated potent anti-inflammatory effects on IL-6 secretion. We investigated whether tart cherry extract or anthocyanins in the tart cherry show additive anti-inflammatory effects with lipitor. Results showed that LPS-induced adipose stem cell secretion of IL-6 reduced with the addition of tart cherry extract, a mixture of tart cherry anthocyanins, and pure tart cherry cyanidin-3-O-glucoside (C3G) in a dose-dependent manner. Furthermore, lipitor and C3G exhibited additive effects in reducing LPS-induced IL-6 secretion from adipose stem cells. We have earlier reported on the bioactive compounds (withanamides) in the fruits of Aswagandha (Withania somnifera) herb that are capable of inhibiting beta amyloid protein that cause Alzheimer's disease and antiinflammatory compounds (withanolides) in its leaves. The metabolomics studies conducted using mass spectroscopy allowed us to determine every single active withanamides and withanolides (total of 74 compounds) in its fruit extract. The results from this study will help the botanical supplements industry to check for quality and standardize the supplements containing Aswagandha for efficacy. In addition, the research on fenugreek spice, ginger grown under organic and conventional agricultural practices, curcuma spp. and Prosopis vegetable all yielded scientific support to the anecdotal health claims associated with them. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Consumers, growers and dietary supplement industry PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Our research continue to provide scientific basis and support to anecdotal health claims associated with a number of traditional foods and botanical supplements available to consumers. The results from our anthocyanin study support potential benefits of using dietary phytochemicals in conjunction with pharmacological therapies to decrease adipose inflammation, drug doses, and ultimately, drug-induced adverse effects. The anthocyanin research has also yielded a US patent for methods and compositions for the treatment of obesity, insulin related diseases and hypercholesterolemia.

Publications

  • R. H. C. Nebie, Y. Liu, M. G. Nair. 2012. Organic ginger (Zingiber officianlis) inhibits COX-1 and -2 enzymes and lipid peroxidation. Journal of West African Chemical Society. 33, 44-51.
  • United States Patent No. 8,198,249. DATE: June 12, 2012.
  • Y. Liu, R. K. Kakani, M. G. Nair. 2012. Compounds in fenugreek spice exhibit antioxidant and antiinflammatory activities. Food Chemistry. 131, 1187-1192.
  • Y. Liu, D. Singh, M. G. Nair. 2012. Pods of Khejri (Prosopis cineraria) consumed as a vegetable showed functional food properties. Journal of Functional Foods. 4, 116-121.
  • K.P. McCook-Russell, M. G. Nair, P. C. Facey, C. S. Bowen-Forbes. 2012. Nutritional and nutraceutical comparison of Jamaican Psidium cattleianum (strawberry guava) and Psidium guajava (common guava) fruits. Food Chemistry. 134, 1069-1073.
  • J. Bolleddula, W. Fitch, S. K. Vareed, M. G. Nair. 2012. Identification of metabolites in Withania somnifera fruits by liquid chromatography and high resolution mass spectrometry. Rapid Communication in Mass Spectrometry. 26, 1277-1290.
  • Y. Liu, M. G. Nair. 2012. Curcuma longa and Curcuma mangga leaves exhibit functional food property. Food Chemistry. 135, 634-640.
  • Z. Zhou, M. G. Nair, K.J. Claycombe. 2012. Synergistic inhibition of interleukin-6 production in adipose stem cells by tart cherry anthocyanins and atorvastatin. Phytomedicine. 19, 878-881.


Progress 01/01/11 to 12/31/11

Outputs
OUTPUTS: The goal of this project is to discover health beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants consumed around the world as a dietary ingredient or as an ingredient in traditional medicines. In 2011, we have published our research findings on Labdane diterpenes in Curcuma mangga rhizomes inhibit lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation, health-beneficial phenolic aldehydes in Antigonin leptopus tea, limonoids with lipid peroxidation activity, neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia and novel stemodin-derived analogues with lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation inhibitory activities. Anthocyanins present in vegetables and fruits are considered to be health-beneficial by many consumers. Therefore, we investigated anthocyanin further for its neuroprotective effect. We used the anthocyanin cyanidin-3-O-glucoside, isolated and purified from tart cherries, against permanent middle cerebral artery occlusion (pMCAO) in mice and its potential mechanisms of neuroprotection. C57BL/6 mice subjected to pMCAO were treated with CG orally. Twenty-four hours after pMCAO, neurological scoring was used to evaluate neurological functional outcome. The brains were then excised for measuring infarct volume and brain superoxide levels were determined. In a separate set of experiments, the influence of CG on cytochrome c (cyt c) and apoptosis-inducing factor (AIF) release from mitochondria under oxidative stress were assessed in isolated cortical neurons from adult mouse brains. Infarction volume was significantly attenuated by 27 percent in mice pre-treated with 2 mg/kg of CG when compared to vehicle-treated mice. Delayed treatment with 2 mg/kg of CG also showed 25percent reduction in infarct size. Neurological functional outcome was significantly improved in mice pre- or post-treated with CG. Compared to vehicle treated mice CG treated mice had lower levels of brain superoxide. CG also blocked the release of AIF from mitochondria under oxidative stress, but did not inhibit the release of cyt c. Our data show that CG is neuroprotective against pMCAO in mice, and this beneficial effect may be mediated by attenuation of brain superoxide levels after ischemia. CG may also exert its neuroprotective effect by blocking AIF release in mitochondria. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Our research has provided scientific basis and support to some of the anecdotal health claims associated with a number of traditional foods and botanical supplements available to consumers with an array of health-beneficial claims. The neuroprotective effect of anthocyanins demonstrated in our in vivo studies indicates that it has the potential to be developed as a prophylactic or as a treatment for stroke in human. This could prevent numerous death associated with stroke.

Publications

  • Y. Liu, M. G. Nair. 2011. Labdane diterpenes in Curcuma mangga rhizomes inhibit lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation. Food Chemistry. 124, 527-532.
  • V. Mulabagal, R. L. Alexander-Lindo, D. L. DeWitt, M. G. Nair. 2011. Health-beneficial phenolic aldehydes in Antigonin leptopus tea. Evidence based Complementary and Alternative medicine (eCAM). Article ID 601249, doi:10.1093/ecam/nep041.
  • R. G. Fowles, B. S. Mootoo, R. S. Ramsewak, A. Khan, A. Ramsubhag, W. F. Reynolds, M. G. Nair. 2011. Limonoids with lipid peroxidation activity. Natural Product Communication. 6, 785-787.
  • J. Min, S-W. Yu, S-H. Baek, K. M. Nair, OK-N. Bae, A. Bhatt, M. Kassab, M. G. Nair, A. Majid. 2011. Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia. Neuroscience Letters. 500, 157-161.
  • F. A. Russell, W. F. Reynolds, M. A. Singh-Wilmot, V. Mulabagal, M. G. Nair, P. B. Reese. 2011. Novel stemodin-derived analogues with lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation inhibitory activities. Phytochemistry. 72, 2361-2368.


Progress 01/01/10 to 12/31/10

Outputs
OUTPUTS: The goal of this project is to discover health beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants consumed around the world as a dietary ingredient or as an ingredient in traditional medicines. In 2010, we have published our research findings on functional food qualities of red and green lettuce; various Capsicum species including Bhut jolokia, the hottest pepper; health beneficial effects of constituents in black pepper; anticancer, antioxidant and anti-inflammatory activities of raspberry and a novel assay method to determine the antioxidant potential of natural plant extracts and pure compounds. Lettuce, is an important leafy vegetable consumed fresh or in salad mixes. We have compared the dietary virtues of selected commercial red and green lettuce varieties grown under field conditions. The extracts were evaluated for their in vitro lipid peroxidation and cyclooxygenase enzyme inhibitory activities. The red lettuce showed higher antioxidant and antiinflammatory activities than the green lettuce. Red lettuce contained an anthocyanin, over and above chicoric acid quercetin glucoside, ferulic and caffeic acids present in both green and red lettuce. We have quantified capsaicin and dihydrocapsaicin content in a variety of hot peppers. Also, we determined their antioxidant, anti-inflammatory and anticancer activities. The primary difference among these hot peppers is their capsaicinoid content which in turn accounted its biological activity. The water extracts of hot peppers contained a number of compounds with activity similar to aspirin, ibuprofen and naproxen. However, one of the compounds showed higher cyclooxygenase-2 enzyme inhibition similar to Celebrex, a prescription non-steroidal anti-inflammatory drug. Our investigation of black pepper revealed that the alkylamides present in black pepper, similar to the heat principle in Capsicum species, also exhibited antioxidant, antiinflammatory and anticancer activities. Fresh or processed berries are considered to be health-beneficial by many consumers. Fruits of closely related species of plants sometimes possess different biological activities. Therefore, we investigated the fruits of several raspberry species for its anthocyanin contents, and lipid peroxidation, cyclooxygenase enzyme and human tumor cell proliferation inhibitory activities. The higher anthocyanin content in the raspberry was correlated to the higher biological activity. Antioxidants scavenge free radicals, singlet oxygen and electrons in cellular redox reactions. The reduction of the yellow MTT to a purple formazan by the mitochondrial enzyme NADPH is the basis of established in vitro cell viability assays. An antioxidant assay has been developed by us utilizing the redox reaction between MTT and selected natural product extracts and purified compounds. This simple, fast and inexpensive MTT antioxidant assay is comparable with the lipid peroxidation inhibitory assay and can be mechanized to achieve high throughput. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Our research has provided scientific basis and support to some of the anecdotal health claims associated with a number of traditional foods and botanical supplements available to consumers with an array of health-beneficial claims. The novel antioxidant assay developed by us shall be an inexpensive tool to discover antioxidant potential of native plants for researchers in countries with minimal research capacity. It may also lead to rapid test kits to determine the antioxidant potential of fruits, vegetables and other food ingredients in the market and hence enhance the quality of such products available to the consumer.

Publications

  • V.Mulabagal, M. Ngouajio, A. Nair, Y. Zhang, A. L. Gottumukkala, M. G. Nair. 2010. In vitro evaluation of red and green lettuce for functional food qualities. Food Chemistry. 118,300-306.
  • Y.Liu, M. G. Nair. 2010. Capsaicinoids in the hottest pepper Bhut Jolokia and its antioxidant and anti-inflammatory activities. Natural Product Communications. 5,91-94.
  • B.Jayaprakasam, K. Padmanabhan, M. G. Nair. 2010. Withanamides in Withania somnifera fruits protect PC12 cells from beta amyloid responsible for Alzheimers disease. Phytotherapy Research. 24, 859-863.
  • Y.Liu, M. G. Nair. 2010. Non-pungent functional food components in water extracts of hot peppers. Food Chemistry. 122,731-736.
  • Y.Liu, V.R. Yadev, B. B. Aggarwal, M. G. Nair. 2010. Inhibitory effects of black pepper (Piper nigrum) extracts and compounds on human tumor cell proliferation, cyclooxygenase enzymes, lipid peroxidation and nuclear transcription factor-kappa-B. Natural Product Communications. 8,1253-1257.
  • C.S. Bowen Forbes, Y. Zhang, M. G. Nair. 2010. Anthocyanin content, antioxidant, antiinflammatory and anticancer properties of blackberry and raspberry. Journal of Food Composition and Analysis. 23, 554-560.
  • Y.Liu, M. G. Nair. 2010. An efficient and economical MTT assay for determining the antioxidant activity of compounds and extracts. Journal of Natural Products. 77, 1193-1195.
  • United States Patent No. 7,658,937, February 9, 2010.
  • United States Patent No. 7,737,121, June 15, 2010.


Progress 01/01/09 to 12/31/09

Outputs
OUTPUTS: The primary objective of this project is to discover health-beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants consumed around the world as a dietary ingredient or as an ingredient in traditional medicines. In 2009, we published our research findings on functional food constituents in St. John's Wert, a dietary supplement sold in the USA, sweet and sour cherry varieties, raspberry varieties and several clones of Vitis vinifera fruits; and health-beneficial qualities of leaf chicory, herbal drinking water and Withania somnifera extracts. The health-beneficial qualities of the fruits and botanical herbs were evaluated based on lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation inhibitory assays in vitro. The extracts from fruits and botanicals were further purified to determine the active constituents present in a daily dose of dietary intake of these plants. We have determined the bioactive constituents in the lipophilic extracts of edible mushrooms Pholiota nameko (nameko), Lentinula edodes (shiitake) and Pleurotus ostreatus (oyster) using in vitro lipid peroxidation (LPO) and cyclooxygenase enzyme (COX) inhibitory assays. The ethyl acetate extract of nameko was the most active against LPO followed by oyster and shiitake and oyster mushroom extracts at 250 ppm. In the COX assay, the ethyl acetate extracts of nameko, shiitake and oyster inhibited COX-1 and -2 enzymes by 39, 34, 54 and 87, 92 and 75 percent, respectively, at 250 ppm. All three extracts showed identical profile with varying concentrations of compounds. A bioassay-guided purification yielded linoleic acid ergosterol, ergosterol peroxide and a spingolipid along with a glyceride fraction as confirmed by spectroscopic methods. All three mushrooms have shown the presence of linoleic acid and ergosterol peroxide as major constituents. Ergosterol was isolated from nameko and shiitake and sphingolipid from shiitake and oyster mushrooms. The fatty acid fraction obtained from oyster mushroom inhibited LPO by 92 percent and COX-1 and -2 enzymes by 43 and 92 percent, respectively, at 25 ppm. Our extensive evaluations of the water extracts of the botanical dietary supplements for lipid peroxidation, anti-inflammatory and human lung, stomach, colon, breast and central nervous system tumor cell proliferation inhibitory activities have provided scientific support to the anecdotal health-beneficial claims associated with these plants/supplements. PARTICIPANTS: M.G. Nair, PI V. Mulabagal, Y. Liu, T. Diyabalanage, C.S. Bowen-Forbes: Postdocotral Fellows D. L. DeWitt, G.A. Lang, D. Holmes,G. S. Howell, M. Ngouajio: Collaborators at MSU G. V. Subbaraju, M. Ramani, R. Aviayan: Collaborators in India G. E. Henry, Petrunak, A. Kester: Collaborators in Susquehanna University Selinsgrove, PA 17870 S. A. Dalavoy, A. Logan: graduate students at MSU B. Sung, B. B. Aggarwal: collaborators at The University of Texas M. D. Anderson Cancer Center, Texas H. Wang: Collaborator at LS9 Inc.100 Kimball way, South San Francisco, CA 94080 G. Mills: Collaborator at Diversified Natural Products, Inc., 506 East State Street Scottville, MI 49454 TARGET AUDIENCES: Consumers of all ages and races, edible mushroom producers, botanical supplement producers, growers of fruits and vegetables,medical practitioners PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Our research has provided scientific basis and support to some of the anecdotal health claims associated with a number of traditional foods and botanical supplements available to consumers with an array of health-beneficial claims.

Publications

  • V. Mulabagal, G. V. Subbaraju, M. Ramani, D. L. DeWitt and M. G. Nair. 2008. Lipid peroxidation, cyclooxygenase enzyme and tumor cell proliferation inhibitory lignans from Justicia species. Natural Product Communications. 3, 1793-1798.
  • E. Petrunak, A. Kester, Y. Liu, C. S. Bowen-Forbes, M. G. Nair and G. E. Henry. 2009. New Benzophenone O-Glucosides from Hypericum ellipticum. Natural Product Communications. 4, 507-510.
  • V. Mulabagal, G. A. Lang, D. L. Dewitt, S. A. Dalavoy and M. G. Nair. 2009. Anthocyanin content, lipid peroxidation and cyclooxygenase enzyme inhibitory activities of sweet and sour cherries. J. Agric. Food Chem. 57, 1239-1246.
  • C. S. Bowen-Forbes, V. Mulabagal, Y. Liu and M. G. Nair. 2009. Ursolic acid analogues: Non-phenolic functional food components in Jamaican raspberry fruits. Food Chemistry. 116, 633-637.
  • G. A. Logan, G. S. Howell and M. G. Nair. 2009. Cyanidin-3-O-glucoside is an important anthocyanin in several clones of Vitis vinifera L. Pinot noir fruits and resulting wine from Michigan and New Zealand. Internet Journal of Enology and Viticulture 5:2 1-12.
  • V. Mulabagal, G. V. Subbaraju, C.V. Rao, C. Sivaramakrishna, D. L. DeWitt, D. Holmes, B. Sung, B. B. Aggarwal and M. G. Nair. 2009. A withanolide sulfoxide from Withania somnifera inhibits nuclear transcription factor-kappa-B, cyclooxygenase-2 and tumor cell proliferation. Phytotherapy Research. 22, 987-992.
  • Y. Liu, V. Mulabagal, C. S. Bowen-Forbes, R. Aviayan and M. G. Nair. 2009. Lipid peroxidation, cyclooxygenase enzyme and human tumor cell proliferation inhibitory compounds in herbal water. Molecular Nutrition and Food Research. 53,1177-1186.
  • V. Mulabagal, H. Wang, M. Ngouajio and M. G. Nair. 2009. Characterization and quantification of health beneficial anthocyanins in leaf chicory (Cichorium intybus) varieties. European Food Research and Technology. 230, 47-53.
  • T. Diyabalanage, M. Vanisree, G. Mills, D. L. Dewitt and M. G. Nair. Liperoxidation and cyclooxygenase enzyme inhibitory compounds from the lipophilic extracts of some culinary-medicinal higher Basidiomycetes mushrooms. International Journal of Medicinal Mushrooms. 4, 375-382, 2009.
  • G. H. Henry, M. Campbell, A. A. Zelinsky, Y. Liu, C. S. Bowen-Forbes, L. Li, M. G. Nair, D. C. Rowley and N. P. Seeram.2009. Bioactive acylphloroglucinols from Hypericum densiflorum. Phytotherapy Research. 23, 1759-1762. Canadian Patent No. 2,354,042. DATE: February 3, 2009.


Progress 01/01/08 to 12/31/08

Outputs
OUTPUTS: The primary objective of this project is to discover health-beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants consumed around the world as a dietary ingredient or as an ingredient in traditional medicines. In 2008, we have published our research findings on non-nutritive functional agents in rattan-shoots consumed by native people in the Philippines, functional food components in Antogonin leptopus tea, health-beneficial qualities of edible mushroom Agrocybe aegerita, lipid peroxidation and cyclooxygenase enzymes inhibitory activities of acidic aqueous extracts of some dietary supplements and a number of bioactive compounds from Brazilian and Indian medicinal plants that are inhibitory to human tumor cell proliferation. We have also reported a study on the Pest-managing activities of native plant extracts from Burkina Faso, Africa and established that anthraquinones from Cassia nigricans are potential insect managing compounds. The steroidal saponins in the tender shoots of rattan consumed by the Kanawan Aytas in the Philippines have shown to be highly effective as antiinflammatory and inhibitory to human tumor cell proliferation in in vitro studies. Similarly, we have isolated and characterized antiinflammatory and tumor cell inhibitory agents in the black poplar mushroom and determined the concentration of these beneficial compounds when one consume this fresh mushroom. Our extensive evaluation of the water extracts of over the counter botanical dietary supplements for lipid peroxidation and antiinflammatory activities have provided scientific support to the anecdotal health beneficial claims associated with these supplements. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Our research has provided scientific basis and support to some of the anecdotal health claims associated with a number of traditional foods and botanical supplements available to consumers with an array of health-beneficial claims.

Publications

  • K. Georges, B. Jayaprakasam, S.S. Dalavoy, M.G. Nair. 2008. Pest-managing activities of Burkina Faso plant extracts and anthraquinones from Cassia nigricans. Bioresource Technology. 99, 2037-2045.
  • T. Diyabalanage, M. Vanisree, G. Mills, D.L. Dewitt, M.G. Nair. 2008. Health-beneficial qualities of edible mushroom Agrocybe aegerita. Food Chemistry. 108, 97-102.
  • P. Raman, D. L. DeWitt, M. G. Nair. 2008. Lipid peroxidation and cyclooxygenase enzymes inhibitory activities of acidic aqueous extracts of some dietary supplements. Phytotherapy Research. 22, 204-212.
  • G. F. Yu, V. Mulabagal, T. Diyabalanage, W. A. Hurtada, D. L. DeWitt, M. G. Nair. 2008. Non-nutritive functional agents in rattan-shoots consumed by native people in the Philippines. Food Chemistry. 110, 991-996.
  • US Patent 7,341,747. DATE: March 11, 2008.
  • M. Vanisree, R. L. Alexander-Lindo, D. L. DeWitt, M. G. Nair. 2008. Functional food components in Antogonin leptopus tea. Food Chemistry. 106, 487-492.


Progress 01/01/07 to 12/31/07

Outputs
The objective of this project is to discover health-beneficial constituents in fruits, vegetables and generally regarded as safe (GRAS) plants. For example, the red coloration of apple skin is mainly due to anthocyanins that are reported to possess health benefits. We have determined the anthocyanin content in three underutilized Malus pumila Mill cultivars, Cranberry, Kerr and Niedzwetzkyana and in Cornus Kousa fruits. Also, we have confirmed the antiinflammatory and antioxidant activities of these anthocyanins. Our analysis revealed that the three apple cultivars studied contained primarily cyanidin glucosyl rutinoside (1) at 99%. The anthocyanin was purified by C-18 Medium Pressure Liquid Chromatography and characterized by NMR spectral methods. The quantification of anthocyanins in M. pumila cultivars revealed that Cranberry, Kerr and Niedzwetzkyana contained 1.12, 0.55 and 0.36 mg per gram fresh weight of 1, respectively. The lipid peroxidation (LPO) and cyclooxygenase enzyme (COX) inhibitory activities of 1 in water were compared with the activities of cyaniding rutinoside (2) and cyaniding glucoside (3) found in cherries and berries. There is a significant increase in LPO and COX enzyme inhibitory activities of anthocyanin when tested in water compared to DMSO as the carrier. The LPO inhibition of anthocyanins 1, 2 and 3 were 53.3, 68.3, and 87.9 percent, respectively, at 0.25 uM concentration. They inhibited COX-1 enzyme by 42.7, 45.2, and 50.4 and COX-2 by 52.7, 61.5, and 68.5 percent, respectively, at 5 uM. The LPO inhibitory values for commercial standards, BHA, BHT and TBHQ were 85, 89 and 94 percent, respectively at 1 uM. Similarly, positive controls aspirin, celecoxib and robecoxib inhibited COX-1 and -2 enzymes by 68.6, 40.7, and 0, and 26.6, 72.2 and 92.4 percent, respectively, at 60, 26, and 32 nM. We have also evaluated the anecdotal medicinal claims of cashew bark tea and stinking toe fruits consumed in the Caribbean and South America. We have established that the components in cashew bark tea has the ability to ameliorate blood glucose levels. The major component in stinking toe fruit was sucrose and hence it was not antidiabetic contrary to the popular claim. However, this fruit contained terpenoid compounds that inhibited COX enzymes suggesting that its consumption may alleviate inflammatory pain.

Impacts
Anthocyanin containing fruits are implicated in decreased coronary heart diseases and promoted as a healthy natural food supplement. Our antiobese and antidiabetic experiments with anthocyanins using high-fat fed mouse models showed less weight gain under high-fat conditions, reduced cholesterol levels, normalcy in glucose regulation, preserved islet architecture and insulin staining. Overall, these data suggested that anthocyanins in fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity and regulate blood glucose.

Publications

  • Vareed, S. K., Schutzki, R. E., Nair, M. G. 2007. Lipid peroxidation, cyclooxygenase enzyme and tumor cell proliferation inhibitory compounds in Cornus kousa. Phytomedicine. 14, 706-709.
  • Hill, E. C., Ngouajio, M., Nair, M. G. 2007. Allelopathic potential of hairy vetch and cowpea methanol and ethyl acetate extracts on weeds and vegetables. Weed Technology. 21, 437-444.
  • Alexander-Lindo, R. L., E. Y. St-A. Morrison, Nair, M. G., McGrowder, D. A. 2007. Effect of the fractions of the hexane extract and stigmast-4-en-3-one isolated from Anacardium occidentale on blood glucose tolerance test in an animal model. International Journal of Pharmacology. 3, 41-47.
  • Bolleddula, J., Alexander-Lindo, R. L., DeWitt, D. L., Nair, M. G. 2007. Terpenoids from stinking toe (Hymnea courbaril) with cyclooxygenase and lipid peroxidation inhibitory activities. Food Chemistry. 105, 485-490.
  • Vanisree, M., van Nocker, S., DeWitt, D. L., Nair, M. G. 2007. Cultivars of apple fruits that are not marketed with potential for anthocyanin production. J. Agric. Food Chem. 55, 8165-8169.
  • US Patent No. 7,195,784. DATE: March 27, 2007 US Patent No. 7,208,182. DATE: April 24, 2007 US Patent No. 7,211,277. DATE: May 1, 2007 US Patent No. 7,264,831. DATE: September 4, 2007 US Patent No. 7,264,832. DATE: September 4, 2007 US Patent No. 7,264,833. DATE: September 4, 2007 US Patent No. 7,270,836. DATE: September 18, 2007 US Patent No. 7,282,593. DATE: October 16, 2007
  • Korean Patent 10-0679367. DATE: January 30, 2007 Korean Patent 10-0687380. DATE: February 20, 2007 Korean Patent 10-0707051. DATE: April 5, 2007


Progress 01/01/06 to 12/31/06

Outputs
The primary objective of this project is to determine and characterize bioactive constituents in Michigan-grown fruits. We have evaluated a number of Cornus fruits and found that they all contain bioactive anthocyanins. Anthocyanin containing fruits are implicated in decreased coronary heart diseases and used in antidiabetic preparations. We have characterized and quantified anthocyanins in the fruits of a number of Cornus spp. In addition, we have purified the most abundant bioactive anthocyanins, cyanidin-3-glucoside, delphinidin-3-glucoside, cyanidin-3-galactoside and pelargonidin-3-galactoside. Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. We have also determined the antiobese and insulin secretion abilities of anthocyanins, delphinidin, cyanidin and pelargonidin-3-O-galactosides, in C57BL/6J mouse model. Mice were initially fed a high fat diet for four weeks and then switched to a high fat diet containing anthocyanins (1g/Kg high fat diet) and ursolic acid (500 mg/Kg high fat diet) for an additional 8 weeks. High fat diet induced glucose intolerance was prevented by anthocyanins and ursolic acid. The anthocyanins treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver including a significant decrease in liver triacylglycerol levels. Anthocyanins and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity and regulate blood glucose. Project II. Anthocyanins were also quantified along with other bioactive constituents in Hibiscus sabdariffa flowers and Amelanchier fruits. Both of these plant materials are used as food ingredients. Similarly, acylpholoroglucinol derivatives from Hypericum prolificum were found to be antioxidant and anti-inflammatory and showed health beneficial effects. Project III. The antioxidant ferulic and caffeic acid phenolics are ubiquitous in plants and abundant in fruits and vegetables. We have synthesized a series of ferulic and caffeic acid esters and tested for tumor cell proliferation, cyclooxygeanse enzymes (COX-1 and -2) and lipid peroxidation inhibitory activities in vitro. In tumor cell proliferation assay, some of these esters showed excellent growth inhibition of colon cancer cells. Several of these phenolics esters showed strong growth inhibition of breast, lung, colon, central nervous system, and gastric human cancer cell lines. In COX enzyme inhibitory assays, ferulic and caffeic acid esters significantly inhibited both COX-1 and COX-2 enzymes. The long chain caffeates, and short chain ferulates were the most active in lipid peroxidation inhibition and showed 60-70 percent activity at 5 ppm concentration.

Impacts
Anthocyanin containing fruits are implicated in decreased coronary heart diseases and promoted as a healthy natural food supplement. Our antiobese and antidiabetic experiments with anthocyanins using high-fat fed mouse models showed less weight gain under high-fat conditions, reduced cholesterol levels, normalcy in glucose regulation, preserved islet architecture and insulin staining. Overall, these data suggested that anthocyanins and ursolic acid present in fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity and regulate blood glucose.

Publications

  • Bolleddula, J., Olson, L.K., Schutzki, R.E., Tai, M-H., Nair, M.G. 2006. Amelioration of obesity and glucose intolerance in high fat fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas). J. Agric. Food Chem. 54: 243-248.
  • Aggarwal, B.B., Ichikawa,H., Garodia, P., Weerasinghe, P., Sethi, G., Bhatt, I.D., Pandey, M. K., Shishodia, S., Nair, M. G. 2006. From traditional Ayurvedic medicine to modern medicine: Identification of therapeutic targets for suppression of inflammation and cancer. Expert Opin. Ther. Targets, 10, 87-118.
  • Adhikari, D.P., Schutzki, R. E., DeWitt, D. L., Nair, M.G. 2006. Effects of Amelanchier fruit isolates on cyclooxygenase enzymes and lipid peroxidation. Food Chemistry. 97, 56-64.
  • Hill, E.C., Ngouajio, M., Nair, M.G. 2006. Differential response of weeds and vegetable crops to aqueous extracts of hairy vetch (Vicia villosa) and cowpea (Vigna unguiculata). HortScience. 41, 695-700.
  • Vareed, S.K., Reddy, M.K., Schutzki, R.E., Nair, M.G. 2006. Tumor cell growth inhibitory anthocyanins in Cornus alternifolia, Cornus controversa, Cornus kousa and Cornus florida fruits. Life Sciences. 78, 777-784.
  • Ichikawa, H., Takada, Y., Shishodia, S., Jayaprakasam, B., Nair, M. G., Aggarwal, B.B. 2006. Withanolide potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis through suppression of nuclear factor (NF)-kB activation and NF-kB-regulated gene expression. Molecular Cancer Therapeutics. 5, 1432-1445.
  • Bolleddula, J., Vanisree, M., Zhang, Y., DeWitt, D. L., Nair, M.G. 2006. Impact of alkyl esters of caffeic and ferulic acids on tumor cell proliferation, cyclooxygenase enzyme and lipid peroxidation. J. Agric. Food Chem. 54, 5375-5381.
  • Christian, K.R., Nair, M.G., Jackson, J.C. 2006. Antioxidant and cyclooxygenase inhibitory activity of Hibiscus sabdariffa. Journal of Food Composition and Analysis. 19, 778-783.
  • Wang, Y., Botolin, D., Xu, J., Christian, B., Jayaprakasam, B., Nair, M.G., Peters, J., Bisik, J., Olson, L. K., Jump, D. B. 2006. Regulation of hepatic elongase and desaturase expression in diabetes and obesity. J. Lipid Res. 47, 2028-2041.
  • Henry, G.E., Raithore, S., Zhang, Y., Jayaprakasam, B., Nair, M.G., Heber, D., Seeram, N.P. 2006. Acylpholoroglucinol derivatives from Hypericum prolificum. J. Nat. Prod. 69, 1645-1648.
  • US Patent No. 7,000,348. DATE: February 21, 2006
  • US Patent No. 7,132,403. DATE: November 7, 2006
  • US Patent No. 7,141,253. DATE: November 28, 2006
  • Chinese Patent No: ZL 99 8 16056.3. DATE: August 16, 2006.


Progress 01/01/05 to 12/31/05

Outputs
Bioactive constituents from several plants are being studied for human health. ProjectI. We have determined the relative inhibition of lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation by natural food colors. The most abundant water-soluble natural food colors are betacyanins and anthocyanins. Similarly, lycopene, bixin, beta carotene and chlorophyll are water-insoluble colors. Pure betanin, bixin, lycopene, chlorophyll, beta carotene and cyanidin-3-O-glucoside were isolated from Beta vulgaris, Bixa orellana, Lycopersicum esculentum, spinacia oleracea, Daucus carrota and Prunus cerasus, respectively. Among the colors tested, betanin, cyanidin-3-O-glucoside, lycopene and beta carotene inhibited lipid peroxidation. However, all pigments tested gave COX-1 and COX-2 inhibition and showed a dose-dependent growth inhibition against breast, colon, stomach, central nervous system and lung tumor cells, respectively. The mixtures of these pigments were also evaluated for their synergistic effects and chemical interactions at various concentrations. The mixture of anthocyanin and betanin negated their efficacy in the cell growth inhibitory assay and did not enhance COX enzyme inhibitory activity. This is the first study of a comparative evaluation and the impact on biological activities of these pigments alone and in combination. ProjectII. We have isolated a series of selective COX-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds. A bioassay guided phytochemical study of the ethyl acetate extract of the seeds of P. kurroa afforded a new triterpenoid and five known triterpenoids. Their structures were established by extensive NMR spectral studies. The inhibition of COX-2 enzyme by these terpenoids at 100 microgram/mL was 38.3,39,37,49.6,25, and 45 percent, respectively. However, these compounds did not inhibit COX-1 enzyme at the same test concentration. ProjectIII. We have synthesized a series of substituted anthraquinones and tested their efficacy against a human filarial parasite Brugia malayi. Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and B. malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Anthraquinones A-S were synthesized by a single step Friedel-Crafts acylation reaction between phthalic anhydrides and substituted benzenes. Antifilarial properties of these synthetic anthraquinones were tested against microfilaria as well as adult male and female worms of B. malayi. The most active anthraquinone was K and showed 100% mortality within 1,5 and 3 days, respectively, against microfilaria, adult male and female worms at 5ppm concentration. Albendazole, an oral drug currently used to treat parasitic infections, was used as a positive control. Methylated products of anthraquinones did not affect the microfilaria. Histological examination of treated adult female parasites showed most of the anthraquinones caused marked effects on intrauterine embryos. Eur.Patent/Invention#1032568,January 26,2005.Kor.Patent/Invention#10-0499293,June 24,2005.

Impacts
The bioactivity evlauation of natural food colors in pure form and combination revelaed that betanin and anthocyanin could negate their efficacies when consumed together. Also, the anthraquinones synthesised based on day lily anthraquinones are potentail antiparasitic agents that could be developed into therapeutic agents to reduce parsitic load of rural poulations in Africa and other developing nations.

Publications

  • Bolleddula, J., Vareed, S.K., Olson, L.K., Nair, M.G. 2005. Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. J. Agric. Food Chem. 53: 28-31.
  • Reddy, M.K., Alexander-Lindo, R.L, Nair, M.G. 2005. Relative inhibition of lipid peroxidation, cyclooxygenase and tumor cell proliferation by natural food colors. J. Agric. Food Chem. 53: 9268-9273.
  • Zhang, Y., Vareed, S.K., Nair, M.G. 2005. Human tumor cell growth inhibition by nontoxic anthocyanidins, the pigments in fruits and vegetables. Life Sciences. 76: 1465-1472.
  • Weil, M.J., Zhang, Y., Nair, M.G. 2005. Tumor cell proliferation and cyclooxygnese enzyme inhibitory constituents in horseradish (Armoracia rusticana) and Wasabi(Wasabia japonica). J. Agric. Food Chem. 53:1440-1444.
  • Dhananjeyan,M.R., Milev,Y., Kron, M.A., Nair, M.G. 2005. Synthesis and Activity of Substituted anthraquinones Against a Human Filarial Parasite, Brugia malayi. J. Med. Chem. 48: 2822-2830.
  • Seeram,N.P.,Adams,L.S., Henning, S.M., Niu,Y., Zhang,Y., Nair, M.G., Heber, D. 2005. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J. Nutr.Biochemistry. 16: 360-367.
  • Adhikari,D.P., Francis,J.A.,Schutzki,R.E.,Chandra, A., Nair, M.G. 2005. Quantification and characterization of cyclooxygenase and lipid peroxidation inhibitory anthocyanins in fruits of Amelanchier. Phytochemical analysis. 16: 175-180.
  • Amaranthus,M.P., Nair,M.G.,Reid, T.C., Steinfeld, D. 2005. Improved Rhizopogon mycorrhizal colonization and foliar nutrient levels in ponderosa pine and Douglas-fir with Myconate. J. Sustainable Forestry. 20: 1-14.
  • Zhang,Y., DeWitt,D.L., Murugesan,S., Nair, M.G. 2005. Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds. Life Sciences. 77: 3222-3230.
  • Vareed, S.K., Reddy, M.K., Schutzki, R.E., Nair, M.G. 2005. Bioactive constituents in Cornus alternifolia, Cornus controversa and Cornus kousa. Annual Meeting of the American Society of Pharmacognosy, Oregon State University, Corvallis, Oregon July 23-27. Abstr. 46:47.
  • K. Georges, B. Jayaprakasam, S. Dalavoy and M.G. Nair. 2005. Efficacy of selected Burkina Faso plant extracts and purified anthraquinones on insect larvae and adult white fly. Annual Meeting of the American Society of Pharmacognosy, Oregon State University, Corvallis, Oregon July 23-27. Abstr. 46:80.
  • B. Jayaprakasam, Y. Zhang and M.G. Nair. 2005. Inhibitory effects of ferulate esters on lipid peroxidation and cyclooxygenase enzymes. Annual Meeting of the American Society of Pharmacognosy, Oregon State University, Corvallis, Oregon July 23-27. Abstr. 46:79.
  • M. K. Reddy, R. L. Alexander-Lindo and M.G. Nair. 2005. Relative potencies of natural food colors based on lipid peroxidation, cyclooxygenase enzymes and human tumor cell proliferation inhibitory activities. Annual Meeting of the American Society of Pharmacognosy, Oregon State University, Corvallis, Oregon July 23-27. Abstr. 46:80.


Progress 01/01/04 to 12/31/04

Outputs
Bioactive constituents from several plants are being studied for human health. I. The aqueous, methanol and ethyl acetate extracts of Cornus spp. fruits and its seed were investigated for insulin secretion activity in vivo using rodent pancreatic beta cells (INS-1). We have determined the ability of anthocyanins and anthocyanidins to stimulate insulin secretion by rodent pancreatic beta cells. The compounds were tested in the presence of 4 and 10 mM glucose concentrations. Our results indicated that cyanidin-3-glucoside and delphindin-3-glucoside were the most effective insulin secretagogues among the anthocyanins and anthocyanidins tested. Animal studies using C57BL/KsJ mice are in progress. These mice are mutants of leptin-receptor and prone to develop hyperphagia, obesity, hyperinsulinemia and hyperglycemia. The effect of Cornus fruits and its components are being evaluated at eh moment. II. A bioassay-guided purification of the methanolic extract of Withania somnifera fruits yielded novel withanamides A-I and withanolides. The structures of these compounds were determined by using FABMS, HRFABMS, 1D- and 2D-NMR spectral and chemical methods. The withanamides possessed novel chemical structures and consisted of serotonin, glucose and long-chain hydroxyl fatty acid moieties. The stereochemistry of the hydroxyl group in the long-chain fatty acid moiety in one of the withanamides was determined by the modified Moshers ester method. Several of the withanamides inhibited lipid peroxidation by 98, 93, 79, 94, 81 and 86 percent, respectively, at 1 ug/mL. Some of them inhibited lipid peroxidation by 90 percent at 0.5 ug/mL. Our results suggest that the potent antioxidant activity exhibited by novel withanamides is probably due to the hydroxylated long-chain acyl group. This is the first report of withanamides, unique serotonin conjugates, from W. somnifera fruits. III. Guggulu, the gum resin from Commiphora mukul, is one of the components of various formulations of traditional Ayurvedic medicine to treat inflammation, obesity and lipid disorders. In Ayurvedic medicine, guggulu is boiled prior to its use. Therefore, guggulu was boiled with water prior to extractions in our study. Bioassay guided isolation of compounds from the methanol extract of guggulu yielded cembrenoids, bicyclic diterpene, guggulusterone derivatives, myrrhanone derivatives, myrrhanol derivative and a lignan. The structures of these compounds were confirmed by spectroscopic methods. Most of these compounds are novel. These compounds were assayed for lipid peroxidation and cyclooxygenase (COX) enzymes inhibitory activities. At 100 ppm, several of these compounds inhibited the lipid peroxidation. Some of these compounds showed selective COX-2 enzyme inhibition. All compounds inhibited COX-1 enzyme at 100 ppm. The lipid peroxidation and COX enzymes inhibitory activities exhibited by compounds isolated from C. mukul may substantiate its use in traditional medicine. US Patent/Invention NO: 6,676,978. DATE: January 13,2004. US Patent/invention No. 6,800615. DATE: October 5,2004. US Patent/Invention No. 6,818,234. DATE: November 16,2004. EPC Patent/Invention No. 0817781. DATE: 2004.

Impacts
The bioactive compounds of withania somnifera has the potential to be developed as a phytomedicine or therapeutics to prevent or treat inflammatory pain in human. Also, anthocyanins have the potential to regulate blood glucose and hence useful in the prevention of insulin dependednt diabetes.

Publications

  • Cichewicz, R.H., Seeram, N.P., Zhang, Y., Nair, M.G. 2004. Anti-tumor effects of novel anthraquinones from daylilies against human cancer cell lines. Life Sciences. 74:1791-1799.
  • Francis, J.A., Jayaprakasam,B., Olson, L.K., Nair, M.G. 2004. Insulin secretagogues from Moringa oleifera with cyclooxygenase and lipid peroxidation inhibitory activities. Helvetica Acta Chimica. 87:317-326.
  • Zhang, Y., Jayaprakasam,B., Seeram,N.P., Olson,L.K., DeWitt, D.L., Nair, M.G. 2004. Insulin production and cyclooxygenase enzyme inhibition by Cabernet sauvignon grape skin compounds. J. Agric. Food Chem. 52:228-233.
  • Beckwith, A.G., Zhang, Y., Seeram, N.P., Cameron, A.C., Nair, M.G. 2004. Relationship of light quantity and anthocyanin production in Pennisetum setaceum. J. Agric. Food Chem. 52:456-461.
  • Jayaprakasam, B., Strasburg, G.M., Nair, M.G. 2004. Potent lipid peroxidation inhibitors from Withania somnifera fruits. Tetrahedron. 60:3109-3121.
  • Zhang,Y., DeWitt,D.L., Murugesan, S., Nair, M.G. 2004. Novel lipid peroxidation and cyclooxygenase enzyme inhibitory tannins from Picrorhiza kurroa seeds. Chemistry & Biodiversity. 1:426-441.
  • Weil,M.J., Zhang, Y., Nair, M.G. 2004. DEHP and colon cancer proliferating desulfosinigrin (DSS) in wasabi (Wasabia japonica). Nutrition and Cancer.48:207-213.
  • Zhang,Y., Cichewicz, R.H., Nair, M.G. 2004. Lipid peroxidation inhibitory compounds from daylily (Hemerocallis fulva) leaves. Life Sciences. 75:753-763. Erratum: 75: 2143-2144.
  • Alexander-Lindo,R.L., Morrison, E.Y. St. A., Nair, M.G. 2004. Effect of stigmast-4-en-3-one and its corresponding alcohol from the bark of Anacardium occidentale (Cashew). Phytotherapy Research. 18:403-407.
  • Tall, J.M., Seeram, N.P., Zhao, C., Nair, M.G., Meyer, R.A. Raja, S.N. 2004. Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat. Behavioural Brain Research. 153:181-188.
  • Jayaprakasam, B., Zhang, Y., Nair, M.G. 2004. Tumor cell proliferation and cyclooxygenase enzyme inhibitory compounds in Amaranthus tricolor. J. Agric. Food Chem. 52:6939-6943.
  • Francis,J.A., Rumbeiha, W.K., Nair, M.G. 2004. Constituents in Easter lily flowers with medicinal activity. Life Sciences. 76:671-683.
  • Rumbeiha, W.K., Francis, J. A., Fitzgerald,S., Nair, M.G., Holan, K., Bugyei, K.A. Simmons, H. 2004. A comprehensive study of Easter lily poisoning in cats. J. Vet. Diagn. Invest. 16:527-541.


Progress 01/01/03 to 12/31/03

Outputs
Bioactive constituents from several plants are being studied for plant, animal and human health. Project 1. Easter lily plants are nephrotoxic to cats. We have determined that the aqueous extract of the flowers are the most toxic to cats. Cats were orally exposed to subfractions of the aqueous flower extract. Urine was analyzed for chemical markers by HPLC. One of the subfractions contained the toxic component(s). HPLC analysis of the urine of the treated cat that showed toxicity confirmed the presence of components in the aqueous fraction of the flower extract. Studies were also conducted with rats and mice to replace cat model and found that the fraction toxic to cats were not toxic to rats and mice. Project 2. Moringa oleifera belongs to the genus Moringaceae. Bioassay directed isolation and purification of the MeOH extract of M. oleifera fruits yielded N-benzyl thiocarbamates, N-benzyl carbamates, benzyl nitriles and a benzyl ester. These compounds induced insulin production in INS-1 rat pancreatic beta cells at 100 ppm. Project 3. Our investigation of Withania somnifera leaves for bioactive compounds yielded several novel withanolides, 2,2,3-trihydroxypiperidine 2-O-sucroside, piperidine 2-one and a biindole. These compounds were tested for their antiproliferative activity on human Lung, Colon, Central Nervous System and Breast tumor cell lines. The inhibitory concentration to afford IC50 for these compounds was determined by MTT assay. Withaferin A and its derivatives exhibited 50 percent inhibitory concentrations ranging from 0.24 to 11.6 micro gram/mL. Viscosalactone B showed 50 percent inhibition at concentrations ranging from 0.32 to 1.04 micro gram/mL whereas its 27-O-glucoside derivative exhibited IC50 between 7.9 and 17.3 micro gram/ml. However, Physagulin D type withanolides showed either weak or no activity at 30 micro gram/mL. Project 4. Picrorhiza kurroa is a small perennial herb from Scrophulariaceae family. It grows in the Himalayan region at elevations of 3000-5000 meters. The bitter rhizomes and seeds of P. kurroa are well known in the Ayurvedic system of medicine and have been traditionally used for thousands of years in India and other Asian countries to treat disorders of liver and upper respiratory tract to reduce fevers, dyspepsia, chronic diarrhea and scorpion sting. In our study, The ethyl acetate extract of the seeds of P. kurroa yielded picrorhiza acid, picrorhizoside A, picrorhizoside B, Picrorhizoside C, (-) shikimic acid, gallic acid, ellagic acid, isocorilagin, 1-O-galloyl-beta-D-glucose, 1,3,6-O-trigalloyl-beta-D-glucose and 1,2,3,4,6-O-pentgalloyl-beta-D-glucose. Several of these are novel and all are isolated for the first time from the seeds of P. kurroa. In addition to COX inhibitory activities, these compounds showed 89.6, 77.3, 56.1, 50.5, 11.0, 86.4, 50.5, 29.2, 70.9, 50.5, 56.5 and 86.1 percent inhibition of lipid peroxidation at 5 micro gram/mL, respectively. The commercial antioxidants BHA (1.8 micro gram/mL), BHT (2.2 micro gram/mL) and TBHQ (1.66 micro gram/mL) inhibited lipid peroxidation at 85.6, 87.1, 81.1percent, respectively.

Impacts
The bioactive compounds of withania somnifera has the potential to be developed as a phytomedicine or therapeutics to prevent or treat inflammatory pain in human. The project on easter lily plants has the potential to develop a diagnostic marker for the easter lily toxicosis in cats and eventually to develop a treatment for easter lily nephrotoxicity in cats.

Publications

  • US Patent/Invention NO: 6,623,743. DATE: September 23, 2003.
  • US Patent/Invention NO: 6,656,914. DATE: December 3, 2003.
  • Dhanenjeyan, M.R., Nair, M.G. 2003. Synthesis of anthraquinones for treatment of Schistosomiasis. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Francis, J.A., Rumbeiha, W.K., Fitzgerald, S.D., Holan, K.M., Nair, M.G. 2003. Preliminary evaluation of Easter lily nephrotoxicity in cats. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Francis, J.A., Nair, M.G. 2003. Lipid peroxidation and cyclooxygenase enzyme inhibitory activities of flowers, leaves and bulbs of Easter lily. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Jayaprakasam,B., Zhang,Y., Seeram, N.P., Nair, M.G. 2003. Growth inhibitory activity of withanolides on human tumor cell lines from Withania somnifera leaves. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Weil, M.J., Zhang,Y., Nair, M.G. 2003. Colon cancer proliferating desulfosinigrin (DSS) in wasabi powder. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Raman, P., Patino, L.C., Nair, M.G. 2003. Detection of metals in selected botanical supplements by inductively couples plasma mass spectrometry. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Silva, D.H.S., Nair, M.G. 2003. Bioactive flavones and tocotrienols from Iryanthera juruensis. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Vareed, S.K., Schutzki, R.E., Nair, M.G. 2003. Anthocyanins and preliminary lipid peroxidation and COX enzyme inhibitory activities of Cornus fruits. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Zhang,Y., Nair, M.G. 2003. Antioxidant and cyclooxygenase enzyme inhibitory compounds from Picorrhiza kurroa seeds. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Rumbeiha, W.K., Francis, J.A., Fitzgerald, S.D., Nair, M.G. 2003. Easter lily poisoning in cats: New findings and a quest for diagnostic markers. Phi Zeta, San Diego, California, October 3 (Abstract).
  • US Patent/Invention NO: 6,576,271. DATE: June 10,2003.
  • Seeram, N.P., Cichewicz,R.H., Chandra, A., Nair, M.G. 2003. Cyclooxygenase inhibitory and antioxidant compounds from crabapple fruits. J. Agric. Food Chem. 51,1948-1951.
  • Kang, S-Y., Seeram, N.P., Bourquin, L.D., Nair, M.G. 2003. Tart cherry anthocyanins inhibit tumor development in Apc Min mice and reduce proliferation of human colon cancer cells. Cancer Letters. 194,13-19.
  • Seeram, N.P., Zhang, Y., Nair, M.G. 2003. Inhibition of proliferation of human cancer cell lines and cyclooxygenase enzymes by anthocyanidins and catechins. Nutrition and Cancer. 46,101-106.
  • Bolleddula, J., Seeram, N.P., Nair, M.G. 2003. Anticancer and antiinflamatory activities of cucurbitacins from Cucurbita andreana. Cancer Letters. 189,11-16.
  • Bolleddula, J., Nair, M.G. 2003. Cyclooxygenase-2 inhibitory withanolides from Withania somnifera leaves. Tetrahedron. 59,841-849.
  • Ramsewak,R.S., Nair,M.G.,Stommel, M., Selanders, L. 2003. In vitro antibiotic activity of monoterpenes and their mixtures against Toe Nail Fungus pathogens. Phytotherapy Research. 17,376-379.
  • Zhang,Y., Mills,G.L., Nair, M.G. 2003. Cyclooxygenase inhibitory and antioxidant compounds from the fruiting body of an edible mushroom, Agrocybe aegerita. Phytomedicine. 10,386-390.
  • Sharma,V., Walia,S., Kumar,J., Nair, M.G., Parmar, B.S. 2003. An efficient method for the purification and characterization of azadirachtins A, B, and H using MPLC and ESIMS. J. Agric. Food Chem. 51,3966-3972.
  • Lambert, K.R., Nair, M.G., Jackson, J.C. 2003. Antioxidant and anti-inflammatory activities of extracts from three Sorrel (Hibiscus sabadariffa) cultivars. Institute of Food Technologists Annual Meeting and IFT Food Expo, Chicago, IL, July 12-16(Abstract).
  • Rumbeiha, W.K., Nair, M.G., Fitzgerald, S.D., Holan, K. Francis, J.A. 2003. Quest for diagnostic markers of Easter lily poisoning in cats. American Association of Veterinary Laboratory Diagnosticians Annual Meeting, San Diego, California, October 9-16, (Abstract).
  • Adhikari, D.P., Schutzki, R.E., Nair, M.G. 2003. Lipid peroxidation and cyclooxygenase enzymes inhibitory activities of Amalanchier spp. fruits. 44th Annual Meeting of the American Society of Pharmacognosy The Changing face of Natural Products Chemistry Chapel Hill, North Carolina, July 12-16(Abstract).
  • Tuntivanich,V., Booren, A.M., Nair, M.G., Strasburg, G.M. 2003. Antioxidant activity of corn fiber oil. 94th AOCS Annual Meeting and Expo, Kansas City, Missouri, May 4-7(Abstract).
  • Momin,R.A., DeWitt, D.L., Nair, M.G. 2003. Inhibition of cyclooxygenase (COX) enzymes by compounds from Daucus carota L. Seeds. Phytotherapy Research. 17,976-979.
  • Bolleddula, J., Zhang,Y., Seeram, N.P., Nair, M.G. 2003. Antiproliferative activity of Withania somnifera leaf components on human tumor cell lines and their structure activity relationships. Life Sciences. 74,125-132.


Progress 01/01/02 to 12/31/02

Outputs
The bioactive phytoceutical constituents from several plants are being studied for antiparasitic, antiinflammatory, antioxidant and anticancer activities. Schistosomiasis is a debilitating disease caused by parasitic trematodes of the genus Schistosoma that afflicts 200 million people worldwide. Daylilies (Hemerocallis spp.) have been used in Asia for the treatment of schistosomiasis. From Hemerocallis fulva `Kwanzo' Kaempfer roots, we have isolated seven new anthraquinones, kwanzoquinones A (1), B (2), C (4), D (5), E (6), F (7), and G (9), two known anthraquinones, 2-hydroxychrysophanol (3) and rhein (8), one new naphthalene glycoside, 5-hydroxydianellin (11), one known naphthalene glycoside, dianellin (10), one known flavone, 6-methylluteolin (12), and alpha tocopherol. The structures of the compounds were elucidated by spectroscopic and chemical methods. Compounds 1-11 and the monoacetates of kwanzoquinones A and B, 1a and 2a, respectively, were tested for their activity against multiple life-stages of Schistosoma mansoni. Compound 3 immobilized all cercariae within 15 s at 3.1 ppm. However, upon removal of the compound, 20 percent of the immobilized cercariae recovered after 24 h. In contrast, compound 6 immobilized cercariae within 12-14 min at 25 ppm. Following removal of the compound, all cercariae died within 24 h. The adult worms were also immobilized within 16 h by compounds 3 and 6 at 50 ppm. None of the compounds had an effect on the schistosomula stage. These anthraquinones are also found to exhibit anticancer activities in our human tumor cell culture assays. In another study, we have evaluated the inhibition of lipid oxidation and Structure-Activity-Related studies of dietary constituents anthocyanins, anthocyanidins and catechins. Similarly, we have investigated antioxidant and cyclooxygenase inhibitory activities of a number of saturated and unsaturated fatty acids found in foods. Several (29) commercially available C-8 to C-24 saturated and unsaturated fatty acids were assayed for cyclooxygenase-I (COX-I) and cyclooxygenase-II (COX-II) inhibitory and antioxidant activities. Among the saturated fatty acids tested at 60 ppm, there was an increase in antioxidant activity with increasing chain length from octanoic acid to myristic acid (C-8-C-14) and a decrease thereafter. All unsaturated fatty acids tested at 60 ppm showed good antioxidant activity except for undecylenic acid, cis-5-dodecenoic acid and nervonic acid. The highest inhibitory activities among the saturated fatty acids tested on cyclooxygenase enzymes, COX-I and COX-II, were observed for the decanoic acid to lauric acid at 100 ppm. Similarly, among the unsaturated fatty acids tested, the highest activities were observed for the cis-8,11,14-eicosatrienoic acid and cis-13,16-docosadienoic acid, at 100 ppm. Also, antitumor and anticarcinogenic activity of Phyllanthus amarus extract was investigated. Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens seeds were promising and has potential to be developed as dietary supplements.

Impacts
The findings of our study on daylily roots provide some scientific basis for the traditional use of this plant for S. mansoni infections in China. The compounds with activity on S. mansoni, reported from daylilies, are further investigated for developing it as a therapeutic drug for the treatment of schistosomiasis. If successful, our research will help to improve the health of millions of people around the world, especially the low-income and under privileged people in the developing countries.

Publications

  • Cichewicz, R.H., Nair, M.G. 2002. Isolation and characterization of stelladerol, a new antioxidant naphthalene glycoside, and other antioxidant glycosides from edible daylily (Hemerocallis) flowers. J. Agric. Food Chem. 50:87-91.
  • Wu, D., Nair, M.G., DeWitt, D.L. 2002. Novel compounds from Piper methysticum Forst (kava kava) roots and their effects on cyclooxygenase enzyme. J. Agric. Food Chem. 50:701-705.
  • Wu, D., Yu, L., Nair, M.G., DeWitt, D. L., Ramsewak, R.S. 2002. Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots. Phytomedicine. 9:41-47.
  • Seeram, N.P., Schutzki,R.E., Chandra, A., Nair, M.G. 2002. Characterization, quantification and bioactivities of anthocyanins in Cornus spp. J. Agric. Food Chem. 50:2519-2523.
  • Henry, G.E., Momin, R.A., Nair, M.G. and DeWitt, D.L. 2002. Antioxidant and cyclooxygenase efficacies of fatty acids found in food. J. Agric. Food Chem. 50:2231-2234.
  • Clifford, L.J., Nair, M.G., Rana, J. and DeWitt, D.L. 2002. Cyclooxygenase and mosquitocidal alkamides from Echinacea purpurea L. (Moench). Phytomedicine. 9:249-254.
  • Momin, R.A., Nair,M.G. 2002. Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens Linn seeds. Phytomedicine. 9:312-318.
  • Rajesh Kumar, N.V., Joy, K.L., Kuttan, G., Ramsewak, R.S., Nair, M.G., Kuttan, R. 2002. Antitumor and anticarcinogenic activity of Phyllanthus amarus extract. J. Ethnopharmacology. 81:17-22.
  • Momin, R.A., Nair, M.G. 2002. Pest managing efficacy of trans-asarone isolated from Daucus carota L. seeds. J. Agric. Food Chem. 50:4475-4478.
  • Seeram, N.P., Nair, M.G. 2002. Inhibition of lipid oxidation and Structure-Activity-Related studies of dietary constituents anthocyanins, anthocyanidins and catechins. J. Agric. Food Chem. 50:5308-5312.
  • Cichewicz, R. H., Lim, K-C., McKerrow, J. H., Nair, M. G. 2002. Kwanzoquinones A-G and other constituents of Hemerocallis fulva Kwanzo roots and their activity against the human pathogenic trematode Schistosoma mansoni. Tetrahedron. 58: 8597-8606.
  • Zhang, Y., Mills, G.L., Nair, M.G. 2002. Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa. J. Agric. Food Chem. 50:7581-7585.
  • King, A., Miller, J.R.,Walker, E., Nair, M.G. 2002. Visual and Chemical factors influencing oviposition be Anopheles gambiae. Annual Meeting of the Entomological Society of America, North Central Branch, Kellogg Center, Michigan State University, March 25 (Abstract).
  • Jayaprakasam, B., Seeram, N.P., Nair, M.G. 2002. Novel bioactivities of cucurbitacins isolated from Cucurbita andreana. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31 (Abstract).
  • Cichewicz, R.H., Lim, K-C., McKerrow, J.H., Nair, M.G. 2002. Kwanzoquinones A-G and other constituents of Hemerocallis fulva "Kwanzo" roots and their activity against the human pathogenic trematode Schistosoma mansoni. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31 (Abstract).
  • Clifford, L.J., Nair, M.G., Pestka, J.J. 2002. The immunostimulatory effects of compounds isolated from Echinacea purpurea (L) moench on murine macrophage cells. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31 (Abstract).
  • Tall, J.M., Seeram, N.P., Nair, M.G., Meyer, R.A., Raja, S.N. 2002. Carrageenan-induced edema and hyperalgesia is suppressed by oral administration of tart cherry extract in the rat. Annual Society Meeting of Neuroscience, Nov. 2-7, Orlando, Florida (Abstract).
  • Weil, M.J., Nair, M.G. 2002. Evaluation of the antioxidant and antiinflammatory activities of wasabi (Wasabia japonica) and horseradish (Armoracia rusticana) extracts. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31 (Abstract).
  • US Patent/Invention NO: 6,344,190. DATE: February 5, 2002.
  • US Patent Invention NO: 6,348,193. DATE: February 19, 2002.
  • Zhang, Y., Nair, M.G. 2002. Cyclooxygenase inhibitory and antioxidant compounds from the skin of Vitis vinifera. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31(Abstract).
  • Kang, S-Y., Bourquin, L.D., Nair, M.G., Seeram, N.P. 2002. Tart cherry anthocyanins and sulindac reduce adenomas in ApcMin mice. Experimental Biology: Meeting Abstracts 565.5 (Abstract).
  • US Patent/ Invention NO: 6,423,365. DATE: July 23, 2002.
  • US Patent/ Invention NO: 6,361,785. DATE: March 26, 2002.
  • Chinese Patent/ Invention NO: ZL97105422.3. DATE: January 16, 2002.
  • Ukrainian Patent/ Invention NO: No. 44759. DATE: March 15, 2002.
  • Francis, J.A., Nair, M.G. 2002. Bioassay directed isolation and identification of compounds from the fruits of Moringa oleifera. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31 (Abstract).
  • Seeram, N.P., Zhang, Y., Nair, M.G. 2002. Inhibitory effects of anthocyanins and catechins on the growth of human cancer cell lines and COX enzymes and their antioxidant activities. 43rd Annual Meeting of the American Society of Pharmacognosy and 3rd Monroe Wall Symposium, New Brunswick, New Jersey, July 27-31 (Abstract).


Progress 01/01/01 to 12/31/01

Outputs
The bioactive phytoceutical constituents from several plants are being studied for antifungal, antibacterial, nematicidal, mosquitocidal, insecticidal, antiinflammatory, antioxidant and anticancer activities. Daylily flowers are utilized as an important ingredient in traditional Asian cuisine and are also valued for their reputed medicinal effects. In our studies of the bioactive methanol and aqueous methanol extracts of lyophilized daylily flowers, we have isolated kaempferol, quercetin, and isorhamnetin glycosides, phenethyl glucopyranoside, orcinol glucopyranoside,phloretin-glucopyranoside,phloretin xylopyranosyl glucopyranoside, a new napthalene-glycoside, stelladerol and an amino acid (longitubanine A). All of these compounds were tested for their antioxidant and cyclooxygenase inhibitory activities. Stelladerol was found to possess strong antioxidant properties inhibiting lipid oxidation by 94.6% 1.4 at 10 micromolar in an in vitro assay. Several of the flavonol 3-O-glycosides isolates also demonstrated modest antioxidant activity. Also, cyclooxygenase enzyme inhibitory assay-guided purification of ethyl acetate extract of kava kava roots yielded six biologically active compounds, and were purified using MPLC, preparative TLC and HPLC methods. These compounds were also evaluated for antioxidant activities. Dihydrokawain and yangonin showed the highest COX-I and COX-II inhibitory activities at 100 ppm, respectively. Lipid oxidation assay did not reveal antioxidant activities for demethoxyyangonin, dihydrokawain, kawain, dihydromethysticin and methysticin at 50 ppm. The antioxidant activities of flavokawain A and yangonin could not be tested in lipid oxidation assay due to solubility problems. However, yangonin and methysticin showed moderate antioxidant activities in free radical scavenging assay at 2.5 ppm. Similarly, studies are under way to isolate antiinflammatory and gap junction intercellular communication active compounds from Echinacea flowers. Bioassay-directed isolation, purification and characterization of bioactive components from carrot seeds, horseradish,and crab apples are in progress.

Impacts
The findings of our study on kava kava roots provide some scientific basis for the traditional use of kava kava roots for managing inflammatory pains. The compounds isolated from the ethyl acetate extract of kava kava roots exhibited both COX-I and COX-II enzyme inhibitory activities and therefore may be responsible for the folkloric use of kava kava roots preparation to alleviate arthritic and gout related pain. This is the first report of the cyclooxygenase inhibitory activities of dihydrokawain, demethoxyyangonin, flavokawain A, kawain, dihydromethysticin, yangonin and methysticin isolated from kava kava roots.

Publications

  • Momin, R.A. M. G. Nair. Mosquitocidal, 2001. nematicidal and antimicrobial compounds from Apium graveolens L. Seeds. J. Agric. Food Chem. 49:142-145,
  • Ries, S. Baughan,R. Nair, M.G.R. Schutzki. 2001. Repelling animals from crops using plant extracts. HortTechnology. 11: 302-307,
  • Nitao, J.K. Birr,B.A. Nair,M.G. Herms, D.A. Mattson, W.J. 2001. Rapid quantification of condensed tannins with a continuous flow analyzer. J. Agric. Food Chem. 49: 2207-2214,
  • Nair,M.G., Wang,H., Strasburg,G.M., Booren, A.M., Gray, J.I. Method for inhibiting cyclooxygenase and inflammation using cherry bioflavonoids. US Patent No. 6,194,469, February 1, 2001.
  • Henry, G.E. Nair, M.G. 2001. Antioxidant and antiinflammatory fatty acids. 42 Annual Meeting of the American Society of Pharmacognosy, Oaxaca, Mexico, July 14-18 (Abstract).
  • Cicchewicz, R.H. Nair, M.G. 2001. Bioactive constituents of Hemerocallis cv. Stella de Oro. 42 Annual Meeting of the American Society of Pharmacognosy, Oaxaca, Mexico, July 14-18 (Abstract).
  • Clifford, L.J. Nair, M.G. 2001. Bioactive compounds from Echinacea purpurea L. Moench. 42 Annual Meeting of the American Society of Pharmacognosy, Oaxaca, Mexico, July 14-18 (Abstract).
  • Momin, R.A. Nair, M.G. 2001. Compounds from Daucus carota L. seeds with phytoceutical potential. 42 Annual Meeting of the American Society of Pharmacognosy, Oaxaca, Mexico, July 14-18 (Abstract).
  • Seeram, N.P.Bourquin, L.D. Nair, M.G.2001. Decomposition products of cyanidin glycosides and benzyl glucosides from tart cherries and their bioactivities. 42 Annual Meeting of the American Society of Pharmacognosy, Oaxaca, Mexico, July 14-18 (Abstract).
  • Wu,D. DeWitt, I.D. Nair, M.G.2001. Cyclooxygenase enzyme active compounds from Piper methysticum (kava kava) roots. 42 Annual Meeting of the American Society of Pharmacognosy, Oaxaca, Mexico, July 14-18 (Abstract).


Progress 01/01/00 to 12/31/00

Outputs
The bioactive phytoceutical constituents from several plants are being studied for anti-fungal, anti-bacterial, nematicidal, mosquitocidal, insecticidal, anti-inflammatory, antioxidant and anti-cancer activities. Tart cherry anthocyanins are being evaluated for the prevention of colon cancer using Min mouse models and in vitro cell culture assays. Anthocyanins are cyanidin from tart cherry are studied for their stability under varying pH and temperature conditions. A study is underway to isolate anti-inflammatory and gap junction intercellular communication active compounds from Piper methysticum (kawa kawa), Echinacea and Hemerocallis spp. Bioassay-directed isolation, purification and characterization of bioactive components from carrot seeds, horseradish, bitter melon and crabapples are in progress. Patent NO: 6,150,408. DATE: November 16, 2000.

Impacts
(N/A)

Publications

  • Seeram, N.P., Lewis, A.W., Jacobs, H., Nair, M.G., McLean, S., Reynolds, W.F. 2000. Proctoriones a-C:2-acylcyclohexane-1,3-dione derivatives from Peperomia proctorii. Journal Natural Products 63:399-402.
  • Kelm, M.A., Nair, M.G., Strasburg, G.M., Chang, Y.C., Booren, A.M., Gray, J.I., DeWitt, D.L. 2000. Antioxidant and cyclo-oxygenase inhibitory phenolic compounds from Ocimum sanctum Linn. Phytomedicine 7:7-13.
  • Wang, H., Nair, M.G., Strasburg, G.M., Chang, Y-C., Booren, A.M., Gray, J.I., DeWitt, D.L. 2000. Cyclo-oxygenase active bioflavonoids from BalatonTM tart cherry and structure their activity relationship. Phytomedicine 7:15-19.
  • Ramsewak, R.S., DeWitt, D.L., Nair, M.G. 2000. Anti-cancer, antioxidant anti-inflammatory activities in curcumins I - III from Curcuma longa. Phytomedicine 7:303-308.
  • Momin, R.A., Ramsewak, R.S., Nair, M.G. 2000. Bioactive compounds and 1,3-di[(cis) -9- octadecenoyl]-2-[(cis,cis)-9,12-octadecadienoyl]glycerol from Apium graveolens L. Seeds Journal Agricultural Food Chemistry 48:3785-3788.
  • Wenzl, P., Chavez, A.L., Mayer, J.E., Rao, I.M., Nair, M.G. 2000. Two dihydroxycinnamoyl quinic acid esters from roots of nutrient-deprived Brachiaria species. Phytochemistry 55:397-401.
  • Arora, A., Valcic, S., Cornejo, S., Nair, M.G., Timmermman, B.N., Leibler, D.C. 2000. Reactions of genestein with alkylperoxyl radicals. Chemical Research in Toxicology 13:638-645.
  • Balasubramanian, S., Ward, D.L., Nair, M.G. 2000. The first isolation and crystal structure of a boron difluoro complex (isoflavone yellow). Biologically active intermediates produced during isoflavone synthesis. Perkin Trans-I 4:567-570.
  • Miles, J.E.C., Ramsewak, R.S., Nair, M.G. 2000. Non-alkaloidal compounds from Delphinium elatum cv. Magic fountains flower-parts. Journal Agricultural Food Chemistry 48:503-506.
  • Powell, J.F., Vargas, J.M., Nair, M.G., Detweiler, A.R., Chandra, A. 2000. Management of dollar spot on creeping bentgrass with metabolites of Pseudomonas aureofaciens (TX-I). Plant Disease 84:19-24.
  • Arora, A., Byren, T.M., Nair, M.G., Strasburg, G.M. 2000. Modulation of liposonal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys 373:102-109.
  • Balasubramanian, S., Nair, M.G. 2000. An efficient one pot synthesis of isoflavones. Synthetic Communications 30:469-484.


Progress 01/01/99 to 12/31/99

Outputs
The bioactive phytoceutical constituents from several plants are being studied for antifungal, antibacterial, nematicidal, mosquitocidal, insecticidal, anti-inflammatory, antioxidant and anti-cancer activities. Tart cherries are being evaluated for anthocyanins and phenolic compounds with anti-inflammatory, antioxidative and anti-cancer activities. Anthocyanins and cyanidin from tart cherry are studied for their efficacy to prevent colon cancer in Min mouse model systems. Bioavailability and mechanism of HAA reduction by athocyanins are also being investigated. A study is under way to isolate anti-inflammatory and gap junction intercellular communication active compounds from Piper methysticum (kawa kawa), Echinacea and Hemerocallis spp. Antifeedant principles and other bioactive components in leather plant (Dirca palustris) are being examined. PATENTS:5,981,775. Date:1999. 5,985,636. Date:1999. 5,993,881. Date:1999.

Impacts
(N/A)

Publications

  • Wang, H., Nair, M.G., Strasburg, G.M., Booren, A.M. and Gray, J.I. 1999. Novel antioxidant and anti-inflammatory compounds from tart cherries. J. Nat. Prod. 62:86-88.
  • Ramsewak, R.S., Nair, M.G., Strawburg, G.M., Dewitt, D.L. and Nitiss, J.L. 1999. Biologically active carbazole alkaloids from Murraya koenigii. J. Agric. Food Chem 47:444-447.
  • Ramsewak, R.S., Erickson, A.J. and Nair, M.G. 1999. Bioactive N-isobutylamides from the flower buds of Spilanthes acmella. Phytochemistry 51:729-732.
  • Wang, H., Nair, M.G., Strasburg, G.M., Booren, A.M. and Gray, J.I. 1999. Antioxidant polyphenols from tart cherries. J. Agric. Food Chem. 47:840-844.
  • Wang, H., Nair, M.G., Strasburg, G.M., Chang, Y-C, Booren, A.M., Gray, J.I. and Dewitt, D.L. 1999. Antioxidant and anti-inflammatory activities of anthocyanins and their aglycone from tart cherries. J. Nat. Prod. 62:294-296.
  • Loskutov, A.V., Beninger, C.W., Ball, T.M., Hosfield, G.L., Nair, M. and Sink, K.C. 1999. Optimization of in vitro conditions for stigma-like-structure production from half-ovary explants of Crocus sativus L. In vitro Cellular and Developmental Biology Plant 35:200-205.
  • Ramsewak, R.S., Nair, M.G., Dewitt, D.L. and Mattson, W.J. 1999. Biologically active phenolic glycosides from Dirca palustris. J. Nat. Prod. 62:1558-1560.


Progress 01/01/98 to 12/31/98

Outputs
The bioactive phytoceutical constituents from several plants are being studied for antifungal, antibacterial, nematicidal, mosquitocidal, insecticidal, anti-inflammatory, anti-oxidant and anti-cancer activities. Tart cherries are being evaluated for anthocyanins and phenolic compounds with anti-inflammatory and anti-oxidative activities. Also, these compounds are studied for their efficacy to prevent colon cancer in Min mouse model systems. A study is under way to isolate nitrification inhibitors from Leucaena leucocephala. Anti-feedant principles and other bioactive components in leather plant are being examined. A water-soluble formulation of formononetin is prepared, and its efficacy as mycorrhiza stimulating agent is being studied.

Impacts
(N/A)

Publications

  • Benninger, C.W., Hosfield, G.L. and Nair, M.G. 1998. Physical characteristics of dry beans in relation to seedcoat color genotype. HortScience 33:328-329.
  • Menon, L.G., Kuttan, R., Nair, M.G., Chang, Y.C. and Kuttan, G. 1998. Effect of isoflavones-genestein and daidzein in the inhibition of lung metastasis in mice induced by B16F10 melanoma cells. Nutrition and Cancer 30:74-77.
  • Roth, G.N., Chandra, A. and Nair, M.G. 1998. Novel bioactivities of Curcuma longa Linn. constituents. J. Nat. Prod. 61:542-545.
  • Arora, A., Nair, M.G. and Strasburg, G.M. 1998. Structure-activity relationships for anti-oxidant activities of a series of flavonoids in a liposomal system. Free Radicals Biology and Medicine 24:1355-1363.
  • Kelm, M.A., Nair, M.G. 1998. Mosquitocidal compounds and a triglyceride, 1,3-dilinoleneoyl-2-palmitin from Ocimum sanctum. J. Agric. Food Chem. 46:3092-3094.
  • Benninger, C.W., Hosfield, G.L. and Nair, M.G. 1998. Flavonol glycosides from the seedcoat of Manteca market class dry bean (Phaseolus vulgaris L.). J. Agric. Food Chem. 46:2906-2910.
  • Arora, A., Nair, M.G. and Strasburg, G.M. 1998. Anti-oxidant activities of isoflavones and their biological metabolites in a liposamal system. Archives of Biochemistry and Biophysics 356:133-141.


Progress 01/01/97 to 12/31/97

Outputs
The bioactive constituents from Curcuma longa rhizomes and leaves are being studied for insecticidal and anticancer compounds. Montmorency and Balaton tart cherries (Prunus)are evaluated for anthocyanins and phenolic compounds with antiinflammatory and antioxidative activities. Also, these compounds are studied for their efficacy to enhance the shelf life of meat and to reduce HAA formation during cooking. A study is under way to isolate nitrification inhibitors from Leucaena leucocephala. Antifeedant principles in ornamental daffodils and leather plant (Dirca palustris)are being examined. A water- soluble formulation of formononetin is prepared and its efficacy as a mycorrhiza stimulating agent is being studied. PATENTS: 5,658,794. DATE;August 19,1997. 5,665,351. Date:September 9,1997. 5,691,275. Date: November 25, 1997.

Impacts
(N/A)

Publications

  • OZAN, A., SAFIR, G.R., NAIR, M.G. 1997. Recovery of exogenously applied isoflavones formononetin and biochanin A from soil and their effects on soil microbial populations. J. Chem. Ecology. 23:247-258.
  • KELM, M.A., NAIR, M.G., SCHUTZKI, R.A. 1997. Mosquitocidal compounds from Magnolia salicifolia. International Journal of Pharmacognosy. 35:84- 90.
  • ANDERSON, S.G., NAIR, M.G., CHANDRA, A., MORRISON, E. 1997. Supercritical carbon dioxide and solvent extraction of Bixa orellana L. Seeds and quantification of trans-bixin by HPLC. Phytochemical Analysis. 8:247-249.
  • CHANDRA, A., NAIR, M.G. 1997. Supercritical carbon dioxide extraction of - and B-carotene from carrot (Daucus carota L.). Phytochemical Analysis. 8: 244-246.
  • SANTELL, R.C., CHANG, Y-C., NAIR, M.G., HELFERICH, W. 1997. Dietary genestein elicits estrogenic effects upon the uterus, mammary gland and the hypothalmic/pituitary axis in rats. Journal of Nutrition. 127:263-269.
  • WANG, H., NAIR, M.G., IEZZONI, A.F., STRASBURG, G.M., BOOREN, A.M., GRAY, J.I. 1997. Quantification and characterization of anthocyanins in Balaton tart cherries. J. Agric. Food Chem. 45:2556-2560.
  • ZHANG, D., NAIR, M.G., MURRY, M., ZHANG, Z. 1997. An insecticidal metabolite from nitrogen fixing Streptomyces griseofuscus, MSU-ZD-033. J. Antibiotic. 50:185-188.
  • ARORA, A., NAIR, M.G., STRASBURG, G.M. 1997. A novel fluorescence assay and model system to evaluate antioxidant efficacy: Application to flavonoids and isoflavonoids. In: Antioxidant Methodology: In vivo and in vitro concepts. O.I. Aruoma and S. Cuppett (eds.), AOCS Press, Champaign, IL.


Progress 01/01/96 to 12/30/96

Outputs
The bioactive constituents from Curcuma longa rhizomes and leaves are being studied for insecticidal and anticancer compounds. Montmorency and Balaton tart cherries are evaluated for anthocyanins and phenolic compounds with antioxidative activity to enhance the meat shelf life and to reduce HAA formation during cooking. A study is under way to isolate nitrification inhibitors, and insecticidal compounds from Leucaena leucocephala. Antifeedant principles in ornamental daffodils are being examined. A water-soluble formulation of formononetin is prepared and its efficacy as mycorrhiza stimulating agent is being studied. US patent is pending for this product.

Impacts
(N/A)

Publications

  • CHANG, Y. C., NAIR, M.G. 1995. Metabolism of daidzein and genestein by intestinalbacteria. J.Nat. Prod. 58:1892-1896.
  • CHANG, Y.C., NAIR, M. G., NITISS, J.L. 1995. Metabolites of anticancer daidzein and genestein and their biological activities. J. Nat. Prod. 58:1901-1905.
  • OZAN, A., NAIR, M. G., SAFIR, G.R. 1996. In vitro effects of plant phenolics on root response activity of Trifolium repens. Allelopathy Journal. 3: 59-64.
  • JOHNSON, K. S., SCHAEFER, J., SCRIBER, M., NAIR, M. 1996. Phenylpropenoid phenolics in sweetbay magnolia as chemical determinants of host use in saturatedsilkmoths (Callosamia), J. Chem. Ecol. 11:1965-1979.
  • OZAN, A., SAFIR, G. R., NAIR, M.G. 1996. Isozyme activity of developing Trifolium-Glomus mycorrhiza and associated effects of the isoflavone formononetin. Allelopathy Journal 3:217-228.
  • CHANDRA, A., NAIR, M.G. 1996. Supercritical carbon dioxide extraction of daidzein and genestein from soybean products. Phytochemical Analysis. 7:259-262.


Progress 01/01/95 to 12/30/95

Outputs
The process for the isolation and purification of taxol and taxanes from ornamental yew clippings was further improved and patented. The bioactive constituents from ornamental Magnolia spp. were investigated for controlling mosquito, gypsy moth, corn ear worm and tobacco horn worm. Similarly, Curcuma longa rhizomes and leaves are being studied for bioactive compounds. Montmorency and baylaton tart cherries are evaluated for antioxidants to enhance the meat shelf life and to reduce HAA formation during cooking. A study is under way to isolate nitrification inhibitors, insecticidal and nematicidal compounds from Lucaena leucocephala. Patent No.: 5,478,736. DATE: December 20, 1995.

Impacts
(N/A)

Publications

  • CHANDRA, A., NAIR, M.G. 1995. Supercritical carbon dioxide extraction and quantification of bioactive neolignans from Magnolia virginiana L. flowers, Planta Medica 61: 192-195.
  • NAIR, M.G., CHANDRA, A., WILLIAMS, D.L., GIBLIN-DAVIS, R.M. 1995. Nematicidal aromatic nitro compounds produced by fermentation of streptomyces spp., Pesticide Science 43: 361-365.
  • CHANDRA, A., NAIR, M.G. 1995. Azalomycin from Streptomyces hygroscopicus, MSU/MN-4- 75B, J. Antibiotic 48: 896-898.


Progress 01/01/94 to 12/30/94

Outputs
A novel process for the isolation and purification of taxol and taxanes from ornamental yew clippings was developed and patented. The effect of postharvest storage on taxol and cephalomannine concentration in Hicksii was determined and found that percentage of these compounds increase on storage. Gopalamicin, an antifungal macrodiolide produced by several soil actinomycetes was characterized and its potential use for controlling fungal pathogens in crops was evaluated. Microwave-mediated synthesis of anticarcinogenic isoflavones genestein, daidzein, biochanin A and formononetin from soybeans were accomplished. These isoflavonoids are reported to have important biological activities such as signal molecule for vesicular arbuscular mycorrhiza and antioxidants in human. Capsaicin and dihydrocapsaicin from scotch bonnet peppers were extracted using supercritical carbon dioxide and were quantified using HPLC. Patent No. :5,279,949. DATE:January 18, 1994. Patent No.: 5,310,754. DATE: May 10, 1994. Patent No.: 5,360,918. DATE: November 1, 1994.

Impacts
(N/A)

Publications

  • NAIR, M.G., CHANDRA, A., THOROGOOD, D.L. 1993. Griseulin, a new nitro-containing bioactive metabolite produced by Streptomyces spp. J. Antibiotic 46: 1762-1763.
  • DUNLAP, W.A., KARACORLU, M., PEYMAN, G.A., NAIR, M.G., RAHIMY, M. PEDROZA, L. 1994. Retinal toxicity of intravitreally injected faeriefungin. Opthalmic Surgery 25: 303-306.
  • YAO, J., NAIR, M.G., CHANDRA, A. 1994. Supercritical carbon dioxide extraction of scotch bonnet and quantification of capsaicin and dihydrocapsaicin. J. Agric. Food Chem. 42: 1303-1305.
  • CHANG, Y-C., NAIR, M.G., SANTELL, R.C., HELFERICH, W. 1994. Microwave mediated synthesis of anticarcinogeneic isoflavones from soybeans. J.Agric. Food.Chem. 42: 1869-1871.
  • ELSON, M.E., KELLY, J.F., NAIR, M.G. 1994. Influence of antifungal compounds from a soil-borne actinomycete on Fusarium spp. in asparagus. J. Chem. Ecolology 20: 2555-2566.
  • SCHUTZKI, R.E., CHANDRA, A., NAIR, M.G. 1994. The influence of postharvest storage on taxol and cephalomannine concentrations in Hicksii (Taxaceae). Phytochemistry 37: 405-408.
  • NAIR, M.G., CHANDRA, A., THOROGOOD,D.L. 1994. Gopalamicin: An antifungal macrodiolide produced by soil actinomycete. J. Agric. Food Chem. 42: 2308-2310.


Progress 01/01/93 to 12/30/93

Outputs
Aromatic nitro compounds, spectinabilin, aureothin and griseuolin, were isolatedfrom four different Streptomyces species and gave insecticidal and nematocidal activities. These compounds were active at 0.1-1 ppm concentrations on Heterodera glycines, Panagrellus redivivus and Caenorhabditis elegans. 100 percent mortality was observed at 5-10 ppm concentrations on 4th instar mosquito larvae, Aedes aegyptii. Benzaldehyde, mandelonitrile and amygdalin was quantified and characterized from the kernels of Montmorency cherry pits. Anthocyanins from different Montmorency cultivars were quantified and characterized. Also, preliminary studies on the stabilization of these anthocyanins were carried out. The oil from the Montmorency cherry kernels were characterized by chemical and spectral methods and found to be 1,3-di((z)-9-octadecenoyl)-2-(z,z-9,12- octadecadienoyl) glycerol. Potential application of this oil in food preparation was also evaluated. Patent No.: 60604 (Taiwan). DATE: February 5,1993. Patent No.: 5,236,949. DATE: August 17, 1993. Patent No.: 5,250,566. DATE: October 5,1993.

Impacts
(N/A)

Publications

  • MELVIN, B.P., NAIR, M.G., VARGAS, J.M., DETWEILER, A.R. 1993. Controlling annual bluegrass (Poa annua L) summer patch disease with faeriefungin. HortScience 28: 195-196.
  • CHANDRA, A., NAIR,M.G. 1993. Quantification of benzaldehyde and its precursors from Montmorency cherry (Prunus cerasus L.) kernels. Phytochemical Analysis 4: 120-123.
  • CHANDRA, A., NAIR, M.G. 1993. Chemical characterization of pit oil from Montmorency (Prunus cerasus L.) cherry. J. Agric. Food Chem 41:879-881.
  • CHANDRA, A., NAIR, M.G., IEZZONI, A. 1993. Novel process for the isolation and stabilization of anthocyanin pigments from Montmorency cherry. J. Agric. Food Chem. 41:1063-1065.
  • NAIR, M.G. 1993. Recent studies on natural products as a source for potential agrochemicals. R. Hollingworth and P. Hedin, eds., ACS Symposium Series Chap. 11.


Progress 01/01/92 to 12/30/92

Outputs
Nematicidal and mosquitocidal aromatic nitro compounds, (-)- and (+)-spectinabilins, aureothin and griseuolin were isolated and characterized by spectral means from the fermentation cultures of Streptomyces griseus var. autotrophicus, MSU 32058/ATCC 53668. Pure (-)-spectinabilin, aureothin and griseuolin were also isolated and characterized from Streptomyces spectinabilis, ATCC 27465, under identical conditions. CD analysis indicated that spectinabilin from S. griseus is scalemic with 50% S(-)-spectinabilin in excess. All compounds showed 100% mortality between 0.1 and 1 mug/ml concentrations when tested on nematodes, Panagrellus redivivus, Caenorhabditis elegans and Heterodera glycines in vitro at 24 h. Mosquitocidal assay on Aedes egyptii gave 100% mortality at 6.25 mug/ml for racemic mixture of spectinabilin and griseuolin and 62.5 mug/ml for (-)-spectinabilin and aureothin. Actinomycetes isolated from an old asparagus field, and compounds produced from the isolate gave moderate control of Fusarium moniliforme and Fusarium oxysporum sp. asparagi in vitro. A potent antifungal compound, gopalamicin, CHO, was isolated and characterized from Streptomyces griseus. This compound was active against many plant pathogens. Pit oil from Montmorency cherry was characterized and found to be 1,3-di((Z)-9-octadecenoyl)-2)((Z,Z)-9,12-octadecadienoyl) glycerol and not the previously reported triolein, 1,2,3-tri(Z)-9-octadecenoyl glycerol.

Impacts
(N/A)

Publications