Source: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY submitted to NRP
IDENTIFICATION AND MECHANISM OF ANTIOXIDATIVE, ANTI-INFLAMMATORY AND ANTIDIABETIC PHYTOCHEMICALS IN FOODS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
HATCH
Reporting Frequency
Annual
Accession No.
0183576
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 1, 2010
Project End Date
Sep 30, 2015
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY
3 RUTGERS PLZA
NEW BRUNSWICK,NJ 08901-8559
Performing Department
Food Science
Non Technical Summary
This project will result in the identification of health promoting and disease preventing substances in fresh and processed foods. The information generated will help American consumers to select daily diets to improve their health. They can also help breeders to produce foods with enhanced amounts of these health beneficial compounds.
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
5021499101020%
5021499200020%
5022235101020%
5022235200020%
5025010101010%
5025010200010%
Knowledge Area
502 - New and Improved Food Products;

Subject Of Investigation
1499 - Vegetables, general/other; 2235 - Herbs and spices; 5010 - Food;

Field Of Science
1010 - Nutrition and metabolism; 2000 - Chemistry;
Goals / Objectives
The objectives of this project are to identify and understand the health promotion phytochemicals in foods and natural resources, and provide guidance so that individuals and families are able to make informed, science-based decisions about their health and well-being. Reactive oxygen species (ROS) and reactive carbonyl species (RCS) are considered to cause various cellular damages and lead to various diseases such as heart disease, cancer and diabetes. In this proposed project, we will seek natural phytochemicals from fresh and processed foods to prevent the formation or trapping these reactive species. The chemical and molecular mechanism for their health beneficial properties will be studied. From our previous experience, we expect to identify several effective phytochemicals for the reduction of ROS and RCS in consumers and promote the health of Americans. The information will be published in refereed journals and presented in national meetings. This project will result in the identification of health promoting and disease preventing substances in fresh and processed foods. The information generated will help American consumers to select daily diets to improve their health. They can also help breeders to produce foods with enhanced amounts of these health beneficial compounds.
Project Methods
(1) Bioassay directed fractionation and identification of natural products. We have extensive expertise in the isolation and structural identification of natural products from plants. Most natural products contain a complex mixture of compounds, and isolation begins with crude extracts. Complex mixtures of extracts from natural products will be fractionated using standard column chromatography. The bioactivity of the fractionated compounds will be established by appropriate bioassays. This process has come to be referred in the literature as bioassay directed fractionation. Specific chemical fractionation will not be started until a fraction shows high activity in the bioassays. Once the bioactive fraction or fractions are identified, various fractionation techniques such as column chromatography, thin layer chromatography and high performance liquid chromatography will be used to isolate the pure compound, bioassays will continue to be used to guide the fractionation. Once the pure active compounds were obtained, they will be identified by HPLC/Mass spectrometry, tandem mass spectrometry, proton and C13 NMR spectrometry as well as various 2D NMR techniques, in some cases, X-ray crystallography will be needed to establish the absolute configuration of the molecules. (2) Evaluating phytochemicals on DPPH radical-scavenging activities. To measure antioxidant activity, the DPPH radical-scavenging assay will be carried out. The antioxidant activity of test compounds is expressed as IC50, which is defined as the concentrations of test compounds required for inhibition of the formation of DPPH radicals by 50%. Vitamin E is used as a positive control. (3) Assay of superoxide radical-scavenging activity. Superoxide radicals are determined using spectrophotometric measurement of the effects of various concentrations of test compounds on the reduction of NBT. The superoxide radical-scavenging activity is expressed as the IC50 value. Superoxide dismutase enzyme (SOD) is used as a positive control. (4) We propose to elucidate the chemical natural and formation mechanism of the adducts between the reactions of catechins and glyoxal and methylglyoxal. The adducts will be isolated, separated by chromatography and identified by extensive mass spectrometry and NMR techniques.

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

Outputs
Target Audience:Our research resulted in the form of publications and technical presentations targeted to the scientific community and general public. This project resulted in the identification of health promoting and disease preventing substances in fresh and processed foods. We intend to help American consumers and world citizens select daily diets which improve their health. This will help food manufacturers with producing food products with enhanced amounts of health beneficial compounds. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Five graduate students obtained their Ph.D degree and two obtained their MS degree during 2013 and 2015 How have the results been disseminated to communities of interest?Our results on the anti-obesity activity of citrus peel polymethoxyflavones have been published in Journal of Agricultural and Food Chemistry in 2013 and BioFactors in 2015. It has also presented to the audiences in the International Conferences of Nutraceuticals and Functional Foods held October 2013 in Taipei, Taiwan. The results on the anti-diabetics activity of Polyglnum multiflorum has presented to the audiences in the International Conferences of Nutraceuticals and Functional Foods held September 2015 in Wuxi, China. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Diabetes is one of the leading causes of death in the United States. The number of people with diabetes has been increasing dramatically, and is expected to reach 366 million worldwide by 2030. Type 2 diabetes, affecting more than 90% of diabetes patients, is strongly associated with oxidative stress and is characterized by insulin resistance. There has been a strong need for safe and effective hypoglycemic agents due to side effects from anti-diabetic drugs. Obesity and chronic inflammation is closed related to Type 2 diabetes. Our project has identified a potent health promoting properties of polymethoxyflavones (PMFs) from orange peel extract, an underutilized byproduct of the citrus industry. We found that PMF has anti-inflammatory, anti-obesity, liver protection and anti-diabetics properties. We have reported our findings in several journal articles in high impact journals. We have also found that a popular anti-ageing herb,Polygonum multiflorum also has a very good anti-diabetic property. More interestingly, this property was only obserbed when the herb is properly processed. We believe our research wll help the citrus industry to have value added to their products. It will give American consumers to utilize this information to prevent obesity as well as diabetes.

Publications

  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Pan, M.H.; Chiou, Y.S.; Chen, L.H.; Ho, C.T. Breast cancer chemoprevention by dietary natural phenolic compounds: Specific epigenetic related molecular targets. Molecular Nutrition & Food Research 2015, 59(1), 21-35.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Zhu, Y.; Zhao, Y.; Wang, P.; Ahmedna, M.; Ho, C.T.; Sang, S. Tea flavanols block advanced glycation of lens crystallins induced by dehydroascorbic acid. Chemical Research in Toxicology 2015, 28(1), 135-143.
  • Type: Journal Articles Status: Accepted Year Published: 2015 Citation: Badmaev, V.; Hatakeyama, Y.; Yamazaki, N.; Noro, A.; Mohamed, F.; Ho, C.T.; Pan, M.H. Preclinical and clinical effects of Coleus forskohlii, Salacia reticulata and Sesamum indicum modifying pancreatic lipase inhibition in vitro and reducing total body fat. Journal of Functional Foods 2015, 15, 44-51.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Kim, H.; Youn, K.; Ahn, M.R.; Kim, O.Y.; Jeong, W.S.; Ho, C.T.; Jun, M. Neuroprotective effect of loganin against A?25-35-induced injury via the NF-?B-dependent signaling pathway in PC12 cells. Food & Function 2015, 6(4), 1108-1116.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Wu, W.K.; Panyod, S.; Ho, C.T.; Kuo, C.H.; Wu, M.S.; Sheen, L.Y. Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota. Journal of Functional Foods 2015, 15, 408-417.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Lai, C.S.; Liao, S.N.; Tsai, M.L.; Kalyanam, N.; Majeed, M.; Majeed, A.; Ho, C.T.; Pan, M.h. Caleb in A inhibits adipogenesis and hepatic steatosis in high-fat diet-induced obesity via activation of AMPK signaling. Molecular Nutrition & Food Research 2015, 59, 1883-1895.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Lai, C.S.; Wu, J.C.; Pan, M.H.; Ho, C.T. Disease chemopreventive effects and molecular mechanisms of hydroxylated polymethoxyflavones. BioFactors 2015, 41(5), 301-313.
  • Type: Journal Articles Status: Published Year Published: 2015 Citation: Lee, M.F; Lai, C.S; Cheng, A.C.; Hou, J.S.; Badmaev, V.; Ho, C.T.; Pan, M.H. Krill oil and xanthigen separately inhibit high fat diet induced obesity and hepatic triacylglycerol accumulation in mice. Journal of Functional Foods 2015, 19(Part B), 913-921.
  • Type: Conference Papers and Presentations Status: Published Year Published: 2015 Citation: Ho, C.T.; Sheen, L.Y.; Li, S. Effect of processing and in vivo metabolism on functional food bioactives. Presented at the Annual Meeting of International Society of Nutraceuticals and Functional Foods, September 20-23, 2015, Wuxi, China.
  • Type: Theses/Dissertations Status: Published Year Published: 2015 Citation: Tang, Wenping. Hypoglycemic effects of stilbene glycoside from Polygonum multiflorum in type 2 diabetes and its mechanism of action. Ph.D. Dissertation, Rutgers University, New Brunswick, NJ.


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

Outputs
Target Audience: The report of this period has been published in referred journals targeting scientific community. We have also presented a paper on bioavailability of food bioactives at the International Union of Food Science and Technology World Congress held in Montreal, Canada on August 17-21, 2014 to research international audiences. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? One PhD student, Dr. Teodoro Rivera has successfully completed his thesis and degree on September 2014. Dr. Rivera is currently wroking for Pepsico, Inc. How have the results been disseminated to communities of interest? The results have been mainly disseminated to scientific community through publications in refereed journals such as Journal of Agricultural and Food Chemistry and Journal of Functional Foods, as well as presented at scientific meetings such as American Chemical Society meeting. What do you plan to do during the next reporting period to accomplish the goals? We will continue use cellular models and high fat diet induced obesity animal models to study the anti-obesity and health-promoting properties of several food extracts and their active components, particularly the polymethoxyflavones from citrus peel. We will publish more papers. We are also plan to write review articles to publish in journals to reach more general audiences.

Impacts
What was accomplished under these goals? Diet-induced obesity and associated Non-Alcohol-Fatty-Liver-Disease (NAFLD) have increased and become a major health problem worldwide. This year weinvestigated the chemopreventive effects of dietary Calebin-A, a natural product from plant, on differentiation of 3T3-L1 adipocytes and high-fat diet (HFD)-induced obesity and hepatic steatosis.The 3T3-L1 preadipocytes were induced to differentiate into adipocytes and treated with Calebin-A for 8 days. Calebin-A effectively and dose-dependently suppressed accumulation of lipid droplets in adipocytes through suppression of adipogenic specific factor peroxisome proliferator-activated receptor (PPAR)g, fatty acid synthase (FAS) and activated acetyl-CoA carboxylase (ACC). In the HFD experiment, C57BL/6J mice were fed HFD with or without Calebin-A (0.25% and 1%) for 12 weeks, and the fat and liver tissues were collected and examined. Dietary Calebin-A effectively decreased weight gain and relative perigonadal, retroperitoneal, mesenteric fat weight in HFD-fed mice. Furthermore, Calebin-A markedly reduced hepatic steatosis and serum level of GOT, GPT, total cholesterol and triacylglycerol. These effects were suggested associated with down-regulation of PPARg, sterol regulatory element-binding protein (SREBP)-1, and particularly, activation of AMP-activated protein kinase (AMPK) a signaling both found in adipocytes and liver tissues.Taken together, these results demonstrated for the first time that Calebin-A suppressed adipocyte differentiation, prevented HFD-induced obesity and improved hepatic steatosis, suggesting a novel application for the prevention and treatment of obesity and associated NAFLD.

Publications

  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Wu, J.C., Tsai, M.L., Lai, C.S., Wang, Y.J., Ho, C.T., Pan, M.H. Chemopreventative effects of tetrahydrocurcumin on human diseases. Food & Function 2014, 5(1), 12-17.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Shao, X., Chen, H., Zhu, Y., Sedighi, R., Ho, C.T., Sang, S. Essential structural requirements and additive effects for flavonoids to scavenge methylglyoxal. Journal of Agricultural and Food Chemistry 2014, 62(14), 3202-3210.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Chiou, Y.S., Wu, J.C., Huang, Q., Shahidi, F., Wang, Y.J., Ho, C.T., Pan, M.H. Metabolic and colonic microbiota transformation may enhance the bioactivities of dietary polyphenols. Journal of Functional Foods 2014, 7, 3-25.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Chen, X.Y., Huang, I.M., Hwang, L.S., Ho, C.T., Li, S., Lo, C.Y. Anthocyanins in blackcurrant effectively prevent the formation of advanced glycation end products by trapping methylglyoxal. Journal of Functional Foods 2014, 8, 259-268.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Lai, Y.S., Chen, W.C., Ho, C.T., Lu, K.H., Lin, S.H., Tseng, H.C., Lin, S.Y., Sheen, L.Y. Garlic essential oil protects against obesity-triggered nonalcoholic fatty liver disease through modulation of lipid metabolism and oxidative stress. Journal of Agricultural and Food Chemistry 2014, 62(25), 5897-5906.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Youn, K., Lee, J., Yun, E.Y., Ho, C.T., Karwe, M., Jeong, W.S., Jun, M. Biological evaluation and in silico docking study of ?-linolenic acid as a potential BACE1 inhibitor. Journal of Functional Foods 2014, 10, 187191.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Ma, N.; Lai, C.S., Chung, C.H., Yang, J.M., Hsu, K.C., Chen, C.Y., Chung, T.S., Li, S., Ho, C.T., Pan, M. 5-Demethyltangeretin is more potent than tangeretin in inhibiting dimethylbenz(a)anthracene (DMBA)-12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin tumorigenesis. Journal of Functional Foods 2014, 11, 528-537.


Progress 10/01/12 to 09/30/13

Outputs
Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? One graduate student will obtain his PhD degree in January 2014. How have the results been disseminated to communities of interest? Our results on the anti-obesity aciticity of citrus peel hydroxylated polymethoxyflavones has been published in Journal of Agricultural and Food Chemistry, it has also presented to the audiences in the International Conferences of Nutraceuticals and Functional Foods held October 2013 in Taipei, Taiwan. What do you plan to do during the next reporting period to accomplish the goals? We will continue study the health promoting properties of citrus peel phytochemicals including their molecular mechanism of antiobesity and anti-diabetes.

Impacts
What was accomplished under these goals? This year our study demonstrated that hydroxylated polymethoxyflavones, phytochemicals of citrus peels, effectively and dose-dependently suppressed accumulation of lipid droplets in adipocytes. Western blot analysis revealed that HPMFs markedly down-regulated adipogenesis related transcription factors PPARg and sterol regulatory element-binding protein (SREBP)-1c as well as downstream target fatty acid binding protein 2 (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). In addition, HPMFs also activated adenosine monophosphate-activated protein kinase (AMPK) signaling in 3T3-L1 adipocytes. Furthermore, administration of HPMFs decreased HFD induced body weight, liver and kidney weight as well as perigonadal, retroperitoneal, mesenteric fat weight in C57BL/6 mice. Administration of HPMFs reduced serum levels of aspartate aminotransferase, alanine aminotransferase, triglycerides, total cholesterol. To summarize, polymethoxyflavones, a group of major phytochemicals found in orange peel, exhibit significant anti-obesity activity. Animal study shows that feeding the extract of orange peel to mice will reduce their body weight, as well as their serum levels of triglycerides and cholesterol. These results indicate as potential to use the orange peel extract as a functional food ingredient infoods or beverages such as juices to help controlobesity.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Charoensinphon, N., Qiu, P., Dong, P., Zheng, J., Naguv, P., Cao, Y., Li, S., Ho, C.T., and Xiao, Hang. 5-Demethyltangeretin inhibits human non-small cell lung cancer cell growth by inducing G2/M cell cycle arrest and apoptosis. Molecular Nutrition & Food Research 2013, 57, 2103-2111.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Coppin, J.P., Xu, Y., Chen, H., Pan, M.H., Ho, C.T., Juliani, R., Simon, J.E., and Wu, Q. Determination of flavonoids and anti-inflammatory activity in Moringa oleifera. Journal of Functional Foods 2013, 5, 1892-1899.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Tang, W., Li, S., Liu, Y., Huang, M.T., and Ho, C.T. Anti-diabetic activity of chemically profiled green tea and black tea extracts in a type 2 diabetes mice model via different mechanisms. Journal of Functional Foods 2013, 5, 1784-1793.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Lai, C.S., Ho, M.H., Tsai, M.L., Li, S., Badmaev, V., Ho, C.T., and Pan, M.H. Suppression of adipogenesis and obesity in high-fat induced mouse model by hydroxylated polymethoxyflavones. Journal of Agricultural and Food Chemistry 2013, 61, 10320-10328.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Pan, M.H., Lai, C.S., Wu, J.C., and Ho C.T. Epigenetic and diseases targets by polyphenols. Current Pharmaceutical Design 2013, 19, 6156-6185.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Ting, Y., Li, C.C., Pan, M.H., Ho, C.T., and Huang, Q. Effect of labile methyl donor on the transformation of 5-demethyltangeretin and related implication on bioactivity. Journal of Agricultural and Food Chemistry 2013, 61, 8100-8107.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Zhao, Q., Ho, C.T., and Huang, Q. Effect of ubiquinol-10 on citral stability and off-flavor formation in O/W nanoemulsion. Journal of Agricultural and Food Chemistry 2013, 61, 7462-7469.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Pan, M.H., Lai, C.S., Wang, H., Lo, C.Y., Ho, C.T., and Li, S. Black tea in chemoprevention of cancer and other human diseases. Food Science and Human Wellness 2013, 2, 13-22.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Tian, H., Yang, X., Ho, C.T., Huang, Q., and Song, S. Development of a solid phase microextraction protocol for the GC-MS determination of volatile off-flavour compounds from citral degradation in oil-in-water emulsions. Food Chemistry, 141, 131-138.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Lai, C.S., Li, S., Liu, C.B., Miyauchi, Y., Suzawa, M., Ho, C.T., and Pan, M.H. Effective suppression of azoxymethane-induced aberrant crypt foci formation in mice with citrus peel flavonoids. Molecular Nutrition & Food Research 2013, 57, 551-555.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Li, S., Lo, C.Y., Pan, M.H., Lai, C.S., and Ho, C.T. Black tea: Chemical analysis and stability. Food & Function 2013, 4, 10-18.


Progress 10/01/11 to 09/30/12

Outputs
OUTPUTS: Obesity is a highly prevalent condition that is related to metabolic disorders. Excessive fat stored in adipose tissue, caused by environmental factors, lifestyle and genetic factors, is associated with numerous metabolic diseases such as cardiovascular disease, insulin resistance, type 2 diabetes, hypertension, fatty liver disease and increased mortality. As caloric intake increases, adipocytes store energy in the form of triacylglycerols that result in enhanced adipogenesis, increased adipose tissue mass, and, consequently, obesity. In obesity, dysfunction of adipose tissue contributes to abnormal cytokines and hormone production in adipocyte and results in metabolic dysfunction. It is believed that a combination of decreased caloric intake and physical exercise is effective for prevention of obesity, but it is difficult to have people to change lifestyle and control diet. Some anti-obesity drugs have been used to treat overweight or obese patients. Nowadays, researchers are increasingly interested in searching for natural products from dietary and edible plants that exhibit anti-obesity activity. A large body of literature shows that many phytochemicals and natural products are used to treat obesity as metabolic stimulates, appetite suppressants and starch blockers, and by regulation of glucose and lipid metabolism, as well as targeting on adipocyte differentiation. This year, we studied the anti-obesity potential of xanthigen. Xanthigen is a source of punicic acid and focoxanthin derived from pomegranate seed and brown seaweed, respectively, with recognized triacylglycerol-lowering effects in humans. However,the mechanism remains to be fully elucidated. In the present study, we investigated the inhibitory effects of Xanthigen, focoxanthin and punicic acid (70% in pomegranate seed oil) on the differentiation of 3T3-L1 pre-adipocytes. We found that Xanthigen potently and dose-dependently suppressed accumulation of lipid droplets in adipocytes, compared to its individual components, focoxanthin and pomegranate seed oil. Western blot analysis revealed that Xanthigen markedly down-regulated the protein levels of key adipogenesis transcription factors peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT/enhancer binding protein (C/EBP) beta and C/EBPdelta, as well as a key enzyme involved in adipogenesis, fatty acid synthase (FAS). We also found that Xanthigen up-regulated the NAD+ dependent histone deacetylases (SIRT1) and activated the AMP-activated protein kinase (AMPK) signaling in differentiated 3T3-L1 adipocytes. In addition, Xanthigen may also stimulate insulin trigger signaling and result in Akt-dependent phosphorylation of forkhead/winged helix O (FoxO)1 and FoxO3a. These results indicate that Xanthigen suppresses adipocyte differentiation and lipid accumulation through multiple mechanisms and may have applications for the treatment of obesity. PARTICIPANTS: In the laboratory, I have one PhD student working on this project. The animal study was conducted in collaboration with Professor Min-Hsiung Pan of the National Kaohsiung Marine University in Taiwan. TARGET AUDIENCES: The targer audiences are medical and nutraceutical researchers and manufacturers. They can use our research to develop new products and to further improve existing products. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
This year our study demonstrated that the Xanthigen, a source of pomegranate seed oil and focoxanthin, significantly suppresses 3T3-L1 adipocytes differentiation and lipid accumulation. Xanthigen exerts significant anti-adipogeneic effect These results provide the molecular mechanism of Xanthigen on suppression of adipocytes differentiation. These findings suggest that Xanthigen may have great potential as a novel agent for the treatment of obesity.

Publications

  • Chen, L.C., Tu, S.H., Huang, C.S., Chen, C.S., Ho, C.T., Lin, H.W., Lee, C.H., Chang, H.W., Chang, C.H., Wu, C.H., Lee, W.S., and Ho, Y.S. Human breast cancer cell metastasis is attenuated by lysyl oxidase inhibitors through down-regulation of focal adhesion kinase and the paxillin-signaling pathway. Breast Cancer Research and Treatment 2012, 134, 989-1004.
  • Lou, S.N., Yu, M.W., and Ho, C.T. Tyrosinase inhibitory components of immature calamondin peel. Food Chemistry 2012, 135, 1091-1096. Lin, V.C.H., Tsai, Y.C., Lin, J.N., Fan, L.L., Pan, M.H., Ho, C.T., Wu, J.Y., and Way, T.D. Activation of AMPK by pterostilbene suppresses lipogenesis and cell cycle progression in p53 positive and negative human prostate cancer cells. Journal of Agricultural and Food Chemistry 2012, 60, 6399-6407.
  • Ho, CT., Pan, M.H., Lai, C.S., and Li, S. Polymethoxyflavones as food factors for the management of inflammatory diseases. Journal of Food and Drug Analysis 2012, 20 (Supplement 1), 337-341.
  • Wang, Y., Ho, C.T. Flavour chemistry of methylglyoxal and glyoxal. Chemical Society Reviews 2012, 41, 4140-4149.
  • Kuo, D.H., Hung, M.C., Hung, C.M., Liu, L.M., Chen, F.A., Shieh, P.C., Ho, C.T. and Way, T.D. Body weight management of burdock (Arctium lappa L.) root is associated with the activation of AMP-activated protein kinase in human HepG2 cells. Food Chemistry 2012, 134, 1320-1326.
  • Chen, R.J., Tsai, S.J., Ho, C.T., Pan, M.H., Ho, Y.S., Wu, C.H., and Wang, Y.J. Chemopreventive effects of pterostilbene on urethane induced lung carcinogenesis in mice via the inhibition of EGFR mediated pathways and the induction of apoptosis and autophagy. Journal of Agricultural and Food Chemistry 2012, 60, 11533-11541.
  • Tsai, M.L., Lai, C.S., Chang, Y.H., Chen, W.J., Ho, C.T., and Pan, M.H. Pterostilbene, a natural analogue of resveratrol, potently inhibits 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin carcinogenesis Food & Function 2012, 3, 1185-1194.
  • Liu, Y.W., Lu, K.H., Ho, C.T., and Sheen, L.Y. Protective effects of Antrodia cinnamomea against liver injury. Journal of Traditional and Complementary Medicine 2012, 2, 284-294.
  • Jan, K.C., Chang, Y.W., Hwang, L.S., and Ho, C.T. Tissues distribution and cytochrome P450 inhibition of sesaminol and its tetrahydrofuranoid metabolites. Journal of Agricultural and Food Chemistry 2012, 60, 8616-8623.
  • Hung, C.M., Su, Y.H., Lin, H.Y., Lin, J.N., Liu, L.C., Ho, C.T., and Way, T.D. Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. Journal of Agricultural and Food Chemistry 2012, 60, 8427-8434.
  • Chu, Y.L., Ho, C.T., Chung, J.G., Rajasekaran, R., and Sheen, L.Y. Allicin induces p53-mediated autophagy in Hep G2 human liver cancer cells. Journal of Agricultural and Food Chemistry 2012, 60, 8363-8371.
  • Kuo, Y.C., Lai, C.S., Tsai, C.Y., Nagabhushanam, K., Ho, C.T., and Pan, M.H. Inotilone suppresses phorbol ester-induced inflammation and tumor promotion in mouse skin. Molecular Nutrition & Food Research 2012, 56, 1324-1332.
  • Weng, C.J., Chou, C.P., Ho, C.T., and Yen, G.C. Molecular mechanism inhibiting human hepatocarcinoma cell invasion by 6-shogaol and 6-gingerol. Molecular Nutrition & Food Research 2012, 56, 1304-1314.
  • Chiou, Y.S. Ma, N.J.L., Sang, S., Ho, C.T., Wang, Y.J., and Pan, M.H. Peracetylated (-)-epigallocatechin-3-gallate (AcEGCG) potently suppresses dextran sulfate sodium-induced colitis and colon tumorigenesis in mice. Journal of Agricultural and Food Chemistry 2012, 60, 3441-3451.
  • Lin, H.Y.,, Hou, S.C., Chen, S.C., Kao, M.C., Yu, C.C., Funayama, S., Ho, C.T., and Way, T.D. (-)-Epigallocatechin gallate induces Fas/CD95-mediated apoptosis through inhibiting constitutive and IL-6-induced JAK/STAT3 signaling in head and neck squamous cell carcinoma cells. Journal of Agricultural and Food Chemistry 2012, 60, 2480-2489.
  • Zhong, Y., Chiou, Y.S., Pan, M.H., Ho, C.T., and Shahidi, F. Protective effects of epigallocatechin gallate (EGCG) derivatives on azoxymethane-induced colonic carcinogenesis in mice. Journal of Functional Foods 2012, 4, 323-330.
  • Lai, C.S., Tsai, M.L., Badmaev, V., Jimenez, M., Ho, C.T., and Pan, M.H. Xanthigen suppresses preadipocyte differentiation and adipogenesis through down-regulation of PPAR gamma and C/EBPs, and modulation of SIRT-1, AMPK and FoxO pathways. Journal of Agricultural and Food Chemistry 2012, 60, 1094-1101.
  • Liao, K.K., Wu, M.J., Chen, P.Y., Huang, S.W., Chiu, S.J., Ho, C.T., and Yen, J.H. Curcuminoids promote neurite outgrowth in PC12 cells through MAPK/ERK- and PKC-dependent pathways. Journal of Agricultural and Food Chemistry 2012, 60, 433-443.
  • Hsu, C.L., Lin, Y.J., Ho, C.T., and Yen, G.C. Inhibitory effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells. Food & Function 2012, 3, 49-57.
  • Pan, M.H., Lai, C.S., Tsai, M.L., Wu, J.C., and Ho, Chi-Tang. Molecular mechanisms for anti-aging by natural dietary compounds. Molecular Nutrition & Food Research 2012, 5, 88-115.
  • Su, J.D., Yen, J.H., Li, S., Weng, C.Y., Lin, M.H., Ho, C.T., and Wu, M.J. 3',4'-Didemethylnobiletin induces Phase II detoxification gene expression and modulates PI3K/Akt signaling in PC12 cells. Free Radical Biology & Medicine 2012, 52, 126-141.


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

Outputs
OUTPUTS: Many phytochemicals will undergo rapid and extensive metabolism after human consumption. It is therefore important to understand the metabolism of phytochemicals and the bioactivity of their metabolites. In this period, we perform studies on the antitumorigenic effect of tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR). Pervious study showed that THC is more active at inhibiting 1,2-dimethylhydrazine (DMH)-induced colonic aberrant crypt foci (ACF) development in mouse colon than CUR, however, the molecular mechanisms are unclear. We investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)-induced colon carcinogenesis in mice. Male ICR mice were injected with AOM (5 mg/kg body weight) twice weekly for two weeks and fed control diet or diets containing different concentrations of CUR and THC, respectively. All mice were sacrificed at 6 and 23 weeks, and colonic tissue were collected and examined. We found that dietary administration of both CUR and THC could reduce polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular levels, the results from western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited the anti-inflammatory activity by decreasing the levels of iNOS and COX-2 through down-regulation of ERK1/2 activation. In addition, dietary feeding with CUR and THC markedly reduced the protein level of connexin-43 (CX-43), an important molecule of gap junction, indicating both CUR and THC might interfering the intercellular communication of crypt cells. These results have been published in Molecular Nutrition & Food Research. PARTICIPANTS: In the laboratory, I have one PhD graudate student working on this project. The animal study has been cooperated with Professor Min-Hsiung Pan of the National Kaohsiung Marine Univeristy in Taiwan. We also have an industry partner, Sabinsa Inc to provide us the research sample. TARGET AUDIENCES: The target audiences are medical and nutraceutical researcher and manufacturer. They can use our generated knowledge to further improve their products. PROJECT MODIFICATIONS: No change at this time.

Impacts
Colorectal cancer is one of the major cancer-related mortality in both man and woman in most developed countries. We have demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary tetrahydrocurcumin against carcinogen-induced colonic tumorigenesis. Tetrahydrocurcumin is the major metabolite of curcumin, the most well-known anti-cancer natural product from tumeric plant. However, curcumin is alos known to undergo extensive and rapid metabolism after ingestion. Our study shows that the metabolite of curcumin is even more active than the original curcumin.

Publications

  • Hung, W.L., Ho, C.T., and Hwang, L.S. (2011). Inhibitory activity of natural occurring antioxidants on thiyl radical-induced trans-arachidonic acid formation. Journal of Agricultural and Food Chemistry, 59: 1968-1973.
  • Pan, M.H.; Lin, Y.T., Lin, C.L., Wei, C.S., Ho, C.T., and Chen, W. (2011). Suppression of heregulin-beta1/HER2-modulated invasive and aggressive phenotype of breast carcinoma by pterostilbene via inhibition of matrix metalloproteinase-9, p38 kinase cascade and Akt activation. Evidence-Based Complementary and Alternative Medicine, Article ID 562187, 12 pages.
  • Pan, M.H., Chiou, Y.S., Wang, Y.J., Ho, C.T., and Lin, J.K. (2011). Multistage carcinogenesis process as molecular targets in cancer chemoprevention by epicatechin-3-gallate. Food and Function, 2: 101-110.
  • Lai, C.S., Tsai, M.L., Cheng, A.C., Li, S., Lo, C.Y., Wang, Y., Xiao, H., Ho, C.T., Wang, Y.J., and Pan, M.H. (2011). Chemoprevention of colonic tumorigenesis by dietary hydroxylated polymethoxyflavones in azoxymethane-treated mice. Molecular Nutrition & Food Research, 55: 278-290.
  • Gosslau, A., Jao, D.L.E., Huang, M.T., Ho, C.T., Evans, D., Rawson, N.E., and Chen, K.Y. (2011). Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo. Molecular Nutrition & Food Research, 55: 198-208.
  • Cheng, A.C., Lee, M.F., Tsai, M.L., Lai, C.S., Lee, J.H., Ho, C.T., and Pan, M.H. (2011). Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells. Food and Chemical Toxicology, 49: 485-493.
  • Chien, Y.L., Ho, C.T., Chiang, B.H., and Hwang, L.S. (2011). Effect of fermentation time on antioxidative activities of Ganoderma lucidum broth using leguminous plants as part of the liquid fermentation medium. Food Chemistry, 126: 1586-1592.
  • Bai, N., He, K., Roller, M., Lai, C.S., Shao, X., Pan, M.H., Bily, A., and Ho, Chi-Tang. (2011). Flavonoids glycosides from Microtea debilis and their cytotoxic and anti-inflammatory effects. Fitoterapia, 82: 168-172.
  • Lin, C.C., Liu, Y., Ho, C.T., and Huang, M.T. (2011). Inhibitory effects of 1,3-bis-(2-substituted-phenyl)-propane-1,3-dione, beta-diketone structural analogues of curcumin, on chemical-induced tumor promotion and inflammation in mouse skin. Food & Function, 2: 78-83.
  • Pan, M.H., Lai, C.S., Wu, J.C., and Ho, C.T. (2011). Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Molecular Nutrition & Food Research, 55: 32-45.
  • Chen, C.S., Lee, C.H., Hsieh, C.D., Ho, C.T., Pan, M.H., Huang, C.S., Tu, S.H., Wang, Y.J., Chen, L.C., Chang, Y.J., Wei, P.L., Yang, Y.Y., Wu, C.H., and Ho, Y.S. (2011). Nicotine-induced human breast cancer cell proliferation attenuated by garcinol through down-regulation of the nicotinic receptor and cyclin D3 proteins. Breast Cancer Research and Treatment, 125: 73-87.
  • Gosslau, A., Li, S., Ho, C.T., Chen, K.Y., and Rawson, N.E. (2011). The importance of natural product characterization in studies of their anti-inflammatory activity. Molecular Nutrition & Food Research, 55, 74-82.
  • Lai, H.C., Wu, M.J., Chen, P.Y., Sheu, T.T., Chiu, S.P., Lin, M.H., Ho, C.T., and Yen, J.H. (2011). Neurotrophic effects of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone: Promotion of neurite outgrowth via cAMP/PKA/CREB pathway in PC12 cells. PLoS ONE, 6(11): e28280.
  • Wu, J.C., Lai, C.S., Badmaev, V., Nagabhushanam, K., Ho, C.T., and Pan, M.H. (2011). Tetrahydrocurcumin, a major metabolite of curcumin, induced autophagic cell death through coordinative modulation of PI3K/Akt-mTOR and MAPKs signaling pathways in human leukemia HL-60 cells. Molecular Nutrition & Food Research, 55: 1646-1654.
  • Qiu, P., Guan, H., Dong, P., Guo, S., Zheng, J., Li, S., Chen, Y., Ho, C.T., Pan, M.H., McClements, D.J., and Xiao, H. (2011). The inhibitory effect of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone on human colon cancer cells. Molecular Nutrition & Food Research, 55: 1523-1532.
  • Pan, M.H.; Chiu, Y.S., Tsai, M.L., and Ho, C.T. (2011). Anti-inflammatory activity of traditional Chinese medicinal herbs. Journal of Traditional and Complementary Medicine, 1: 8-24.
  • Lin, N.C., Lin, J.C., Chen, S.H., Ho, C.T., and Yeh, A.I. (2011). Effect of goji (Lycium barbarum) on expression of genes related to cell survival. Journal of Agricultural and Food Chemistry, 59: 10088-10096.
  • Hung, C.M., Kuo, D.H., Chou, C.H., Su, Y.C., Ho, C.T., and Way, T.D. (2011). Osthole suppresses HGF-induced epithelial-mesenchymal transition via repressing c-Met/Akt/mTOR pathway in human breast cancer cells. Journal of Agricultural and Food Chemistry, 59: 9683-9690.
  • Shen, D., Pan, M.H.; Wu, Q.L., Park, C.H., Juliani, H.R., Ho, C.T., and Simon, J. E. (2011). A rapid LC/MS/MS method for the analysis of nonvolatile antiinflammatory agents from Mentha spp. Journal of Food Science, 76: C900-C908.
  • Sang, S., Lambert, J.D., Ho, C.T., and Yang, C.S. (2011). The chemistry and biotransformation of tea constituents. Pharmacological Research, 64: 87-99.
  • Di, R., Huang, M.T., and Ho, C.T. (2011). Anti-inflammatory activities of mogrosides from Momordica grosvenori in murine macrophages and a murine ear edema model. Journal of Agricultural and Food Chemistry, 59: 7474-7481.
  • Hou, J.P., Wu, H., Ho, C.T., and Weng, X.C. (2011). Antioxidant activity of polyphenolic compounds from Dalbergia odorifera T. Chen. Pakistan Journal of Nutrition, 10: 694-701.
  • Tang, W., Chen, L.H., Daun, H., Ho, C.T., and Pan, M.H. (2011). Inhibitory effects of hexahydro-beta-acids in LPS-stimulated murine macrophage. Journal of Functional Foods, 3: 215-222.
  • Lai, C.S., Lai, Y.S., Kuo, D.H., Wu, C.H., Ho, C.T., and Pan, M.H. (2011). Magnolol potently suppressed lipopolysaccharide-induced iNOS and COX-2 expression via downregulating MAPK and NF-keppaB signaling pathways. Journal of Functional Foods, 3: 198-206.
  • Lu, W.C., Huang, W.T., Kumaran, A., Ho, C.T., and Hwang, L.S. (2011). Transformation of proanthocyanidin A2 to its isomers under different physiological pH conditions and common cell culture medium. Journal of Agricultural and Food Chemistry, 59: 6214-6220.
  • Yang, X., Tian, H., Ho, C.T., and Huang, Q. (2011). Inhibition of citral degradation by oil-in-water nanoemulsions combined with antioxidants. Journal of Agricultural and Food Chemistry, 59: 6113-6119.
  • Chang, H.Y., Kuo, M.C., Way, T.D., Ho, C.T., and Fu, E. (2011). Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition by down-regulation of Mdm2 and vimentin. Journal of Agricultural and Food Chemistry, 59: 5357-5363.
  • Yen, J.H., Weng, C.Y., Li, S., Lo, Y.H., Pan, M.H., Fu, S.H., Ho, C.T., and Wu, M.J. (2011). Citrus flavonoid 5-demethylnobiletin suppresses scavenger receptor expression in THP-1 cells and alters lipid homeostasis in HepG2 liver cells. Molecular Nutrition & Food Research, 55: 733-748.
  • Pan, M.H.; Hong, H.M., Lin, C.L., Jhang, A.Z., Tsai, J.H., Badmaev, V., Nagabhushanam, K., Ho, C.T., and Chen, W.J. (2011). Se-methylselenocysteine inhibits lipopolysaccharide-induced NF-keppaB activation and iNOS induction in RAW 264.7 murine macrophages. Molecular Nutrition & Food Research, 55: 723-732.
  • Lv, L., Chen, H., Ho, C.T., and Sang, S. (2011). Chemical components of the root of noni (Morinda citrifolia) and their cytotoxic effects. Fitoterapia, 82: 704-708.
  • Chiou, Y.S., Tsai, M.L., Nagabhushanam, K., Wang, Y.J., Wu, C.H., Ho, C.T., and Pan, M.H. (2011). Pterostilbene is more potent than resveratrol in preventing azoxymethane (AOM)-induced colon tumorigenesis via activation of the NF-E2-related factor 2 (Nrf2)-mediated antioxidant signaling pathway. Journal of Agricultural and Food Chemistry, 59: 2725-2733.
  • Lai, C.S., Wu, J.C., Yu, S.F., Badmaev, V., Nagabhushanam, K., Ho, C.T., and Pan, M.H. (2011). Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis. Molecular Nutrition & Food Research, 55: 1819-1828.
  • Wei, G.J., Ho, C.T., and Huang, A.S. (2011). Analysis of volatile compounds in noni fruit (Morinda citrifolia L.) juice by steam distillation-extraction and solid phase microextraction coupled with GC-AED and GC-MS. Journal of Food and Drug Analysis, 19: 33-39.
  • Lv, L., Shao, X., Chen, H., Ho, C.T., and Sang, S. (2011). Genistein inhibits advanced glycation end products formation by trapping of methylglyoxal. Chemical Research in Toxicology, 24: 579-586.
  • Qiu, P.,; Guan, H.,; Dong, Ping; Li, S.,; Ho, C.T., Pan, M.H.; McClements, D.J., and Xiao, H. (2011). The p53, Bax, and p21-dependent inhibition of colon cancer cell growth by 5-hydroxy polymethoxyflavones. Molecular Nutrition & Food Research, 55: 613-622.
  • Jan, K.C., Ku, K.L., Chu, Y.H., Hwang, L.S., and Ho, C.T. (2011). Intestinal distribution and excretion of sesaminol and its tetrahydrofuranoid metabolites in rats. Journal of Agricultural and Food Chemistry, 59: 3078-3086.
  • Liu, CB., Chen, L.H., Cheng, A.C., Chen, W.J., Tsai, M.L., Liu, Y., Ho, C.T., and Pan, M.H. (2011). Hexahydro-beta-acids induce apoptosis through mitochondrial pathway, GADD153 expression, and caspase activation in human leukemia cells. Food and Chemical Toxicology, 49: 1033-1042.
  • Tu, S.H., Ku, C.Y., Ho, C.T., Chen, C.S., Huang, C.S., Lee, C.H., Chen, L.C., Pan, M.H., Chang, H.W., Chang, C.H., Chang, Y.J., Wei, P.L., Wu, C.H., and Ho, Y.S. (2011). Tea polyphenol (-)-epigallocatechin-3-gallate inhibits nicotine- and estrogen-induced alpha-9-nicotinic acetylcholine receptor upregulation in human breast cancer cells. Molecular Nutrition & Food Research, 55: 455-466.


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

Outputs
OUTPUTS: I have co-organized a symposium on "Reactive Carbonyl Species: Chemistry and Health Effects" for the 239th American Chemical Society National Meeting held on March 21-25, 2010 in San Francisco, CA. My students and I have delivered four research papers on "Reactive carbonyl species and advanced glycation end-products in foods", "Trapping of reactive dicarbonyl species by dietary flavonoids: novel strategy to inhibit the formation of advanced glycation end products", "Inhibition of advanced glycation end products through trapping of methylglyoxal by stilbene glycoside from Polygonum multiflorium Thumb", and "Trapping of methylglyoxal, a Maillard reaction generated bioactive compound, by black currant pigments". I have been invited to give a plenary lecture on "Nutraceuticals targeting the inhibition of free radical-induced trans-fatty acid" for the Annual Meeting for International Society for Nutraceuticals and Functional Foods" on October 11-15, 2010 in Bali, Indonesia. PARTICIPANTS: Professor Chi-Tang Ho (PI): Designs, supervises and executes various research goals. Dr. Shengmin Sang (Collaborator) at North Carolina Agricultural and Technical University, works together with PI on trapping of methylglyoxal with phytopolyphenols. Dr. Min-Hsiung Pan (Collaborator) at the National Kaohsiung Marine University of Taiwan, works together with PI on effects of phytochemicals on age and inflammation related diseases. TARGET AUDIENCES: Papers presented to professional Society such as American Chemical Society and International Society on Nutraceuticals and Functional Foods to reach audiences including food scientists, nutritionists, and health care professionals. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Methylglyoxal (MGO), the reactive dicarbonyl intermediate generated during the nonenzymatic glycation between reducing sugars and amino groups of proteins, lipids, and DNA, is the precursor of advanced glycation end products (AGEs). Many studies have shown that AGEs play a major pathogenic role in diabetes and its complications. We found that 2,3,5,4'-tetrahydroxyl stilbene 2-O-beta-D-glucoside (THSG), the major bioactive compound from Polygonum multiflorum Thunb, could efficiently inhibit the formation of AGEs through trapping reactive MGO in a dose-dependent manner under physiological conditions (pH 7.4, 37C). More than 60% MGO was trapped by THSG within 24 h, which was much more potent than resveratrol and its methylated derivative, pterostilbene, the two major bioactive dietary stilbenes. We successfully purified the major mono- and di-MGO adducts of THSG and found that they were mixture of tautomers. Our LC/MS and NMR data showed that positions 4 and 6 of the A ring were the major active sites for trapping MGO. We also found that THSG could significantly inhibit the formation of AGEs in the human serum albumin (HSA)-MGO assay and both mono- and di-MGO adducts of THSG were detected in this assay using LC/MS. Our results suggest that THSG is a potential natural inhibitor of AGEs through trapping reactive dicarbonyl species. In a similar study, we have found that genistein, a naturally occurred isoflavone derived from soy products, also demonstrated significant trapping effects of MGO and consequently form mono- and di-MGO adducts under physiological conditions (pH 7.4, 37 C). More than 80.0 % MGO was trapped within 4 h. The reaction adducts formed from genistein and MGO under different ratios, were analyzed using LC/MS. We also successfully purified and identified the major mono- and di-MGO conjugated adducts of genistein. The NMR data showed that positions 6 and 8 of the A ring of genistein were the major active sites for trapping MGO. We further demonstrated that genistein could effectively inhibit the formation of AGEs in the human serum albumin (HSA)-MGO assay and both two mono-MGO and one di-MGO adducts of genistein were detected in this assay using LC/MS. Our results indicate that dietary flavonoids that have the same A ring structure as genistein may have the potential to inhibit the formation of AGEs through trapping reactive dicarbonyl species. For the inhibition of reactive oxygen species, we have studied the active components in ginger. Most researchers have considered gingerols as the active principles and have paid little attention to shogaols, the dehydration products of corresponding gingerols during storage or thermal processing. In this study, we have purified and identified eight major components including three major gingerols and corresponding shogaols from ginger extract and compared their anti-carcinogenic and anti-inflammatory activities. Our results showed that shogaols ([6]-, [8]-, and [10]-) had much stronger growth inhibitory effects than gingerols ([6]-, [8]-, and [10]-) on H1299 human lung cancer cells and HCT-116 human colon cancer cells, especially prominent when comparing [6]-shogaol with [6]-gingerol.

Publications

  • Lee, Y.H., Charles, A.L., Kung, H.F., Ho, C.T., and Huang, T.C. (2010). Extraction of nobiletin and tangeretin from Citrus depressa Hayata by supercritical carbon dioxide with ethanol as modifier. Industrial Crops and Products, 31: 59-64.
  • Pan, M.H., Lin, C.L., Tsai, J.H., Ho, C.T., and Chen, W.J. (2010). 3,5,3',4',5'-pentamethoxystilbene (MR-5), a synthetically methoxylated analogue of resveratrol, inhibits growth and induces G1 cell cycle arrest of human breast carcinoma MCF-7 cells. Journal of Agricultural and Food Chemistry, 58: 226-234.
  • Shih, Y.L., Liu, H.C., Chen, C.S., Hsu, C.H., Pan, M.H., Chang, H.W., Chang, C.H., Chen, F.C., Ho, C.T., Yang, Y.Y., and Ho, Y.S. (2010). Combination treatment with luteolin and quercetin enhances anti-proliferation effects in nicotine-treated MDA-MB-231 cells through down-regulating nicotinic acetylcholine receptors. Journal of Agricultural and Food Chemistry, 58: 235-241.
  • Liao, C.D., Hung, W.L., Jan, K.C., Yeh, A.I., Ho, C.T., and Hwang, L.S. (2010). Nano/sub-microsized lignan glycosides from sesame meal exhibit higher transport and absorption efficiency in Caco-2 cell monolayer. Food Chemistry, 119: 896-902.
  • Liao, C.D., Hung, W.L., Lu, W.C., Jan, K.C., Shih, D.Y.C., Yeh, A.I., Ho, C.T., and Hwang, L.S. (2010). Differential tissue distribution of sesaminol triglucoside and its metabolites in rats fed with lignan glycosides from sesame meal with or without nano/sub-micronizing. Journal of Agricultural and Food Chemistry, 58: 563-569.
  • Huang, T.C., Teng, K.C., Liou, Y.Y., Ho, C.T., Liu, H.J., and Chuang, K.P. (2010). Diallyl disulphide, but not diallyl sulphide, increases leukocyte function associated antigen-1 expression and cellular adhesion in monocytes. Food Chemistry, 120: 113-120.
  • Bai, N., He, K., Zhou, Z., Tsai, M.L., Zhang, L., Quan, Z., Shao, X., Pan, M.H., and Ho, C.T. (2010). Ent-Kaurane diterpenoids from Rabdosia rubescens and their cytotoxic effects on human cancer cell lines. Planta Medica, 76: 140-145.
  • Dong, P., Qiu, P., Zhu, Y., Li, S., Ho, C.T., McClements, D.J., and Xiao, H. (2010). Simultaneous determination of four 5-hydroxy polymethoxyflavones by reversed-phase high performance liquid chromatography with electrochemical detection. Journal of Chromatography A, 1217: 642-647.
  • Lo, Y.H., Pan, M.H., Li, S., Yen, J.H., Kou, M.C., Ho, C.T., and Wu, M.J. (2010). Nobiletin metabolite, 3',4'-dihydroxy-5,6,7,8-tetramethoxyflavone, inhibits LDL oxidation and down-regulates scavenger receptor expression and activity in THP-1 cells. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1801: 114-126.
  • Lv, L., Shao, X., Wang, L., Huang, D., Ho, C.T., and Sang, S. (2010). Stilbene glucoside from Polygonum multiforum Thunb.: A novel natural inhibitor of advanced glycation end product formation by trapping of methylglyoxal. Journal of Agricultural and Food Chemistry, 58: 2239-2245.
  • Li, S., Wang, Y., Wang, Z., Xiao, H., Lo, C.Y., Rawson, N., and Ho, C.T. (2010). Quantitative analysis of hydroxylated polymethoxyflavones by high-performance liquid chromatography. Biomedical Chromatography, 24: 836-845.
  • Kuo, D.H., Kang, W.H., Shieh, P.C., Chen, F.A., Chang, C.D., Tsai, M.L., Cheng, A.C., Ho, C.T., and Pan, M.H. (2010). Protective effect of Pracparatum mungo extract on carbon tetrachloride-induced hepatotoxicity in rats. Food Chemistry, 123: 1007-1012.
  • Qiu, P., Dong, P., Guan, H., Li, S., Ho, C.T., Pan, M.H., McClements, D.J., and Xiao, H. (2010). Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells. Molecular Nutrition & Food Research, 54: S244-S252.
  • Chiou, Y.S., Tsai, M.L., Wang, Y.J., Cheng, A.C., Lai, W.M., Badmaev, V., Ho, C.T., and Pan, M.H. (2010). Pterostilbene inhibits colorectal aberrant crypt foci (ACF) and colon carcinogenesis via suppressing multiple signal transduction pathways in azoxymethane-treated mice. Journal of Agricultural and Food Chemistry, 58: 8833-8841.
  • Wu, H., Hsieh, M.C., Lo, C.Y., Liu, C.B., Sang, S., Ho, C.T., and Pan, M.H. (2010). 6-Shogaol is more effective than 6-gingerol and curcumin in inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mice. Molecular Nutrition & Food Research, 54: 1296-1306.
  • Pan, M.H., Lai, C.S., and Ho, C.T. (2010). Anti-inflammatory activity of natural dietary flavonoids. Food & Function, 1: 15-31.
  • Weng, C.J., Wu, C.F., Huang, H.W., Ho, C.T., and Yen, G.C. (2010). Anti-invasion effects of 6-shogaol and 6-gingerol, two active components in ginger, on human hepatocarcinoma cells. Molecular Nutrition & Food Research, 54: 1618-1627.
  • Lin, C.C., Huang, M.T., and Ho, C.T. (2010). Dibenzoylmethane altered adipose mass, serum lipid and sex steroid hormone in female mice. Journal of Food and Drug Analysis, 18: 339-345.
  • Cheng, A.C., Tsai, M.L., Liu, C.M., Lee, M.F., Nagabhushanam, K., Ho, C.T., and Pan, M.H. (2010). Garcinol inhibits cell growth in hepatocellular carcinoma Hep3B cells through induction of ROS-dependent apoptosis. Food & Function, 1: 301-307.
  • Chen, R.J., Ho, C.T., and Wang, Y.J. (2010). Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells. Molecular Nutrition & Food Research, 54: 1819-1832.
  • Shao, X., Lv, L., Parks, T., Wu, H., Ho, C.T., and Sang, S. (2010). Quantitative analysis of ginger components in commercial products using liquid chromatography with electrochemical array detection. Journal of Agricultural and Food Chemistry, 58: 12608-12614.
  • Weng, C.J., Wu, C.F., Huang, H.W., Wu, C.H., Ho, C.T., and Yen, G.C. (2010). Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells. Journal of Agricultural and Food Chemistry, 58: 2886-2894.
  • Shieh, P.C., Chen, Y.O., Kuo, D.H., Chen, F.A., Tsai, M.L., Chang, I.S., Wu, H., Sang, S., Ho, C.T., and Pan, M.H. (2010). Induction of apoptosis by [8]-shogaol via reactive oxygen species generation, glutathione depletion and caspase activation in human leukemia cells. Journal of Agricultural and Food Chemistry, 58: 3847-3854.
  • Bai, N., He, K., Roller, M., Lai, C.S., Shao, X., Pan, M.H., and Ho, C.T. (2010). Flavonoids and phenolic compounds from Rosmarinus officinalis. Journal of Agricultural and Food Chemistry, 58: 5363-5367.
  • Bai, N., He, K., Zhou, Z., Lai, C.S., Zhang, L., Quan, Z., Shao, X., Pan, M.H., and Ho, C.T. (2010). Flavonoids from Rabdosia rubescens exert anti-inflammatory and growth inhibitory effect against human leukemia HL-60 cells. Food Chemistry, 122: 831-835.
  • Shao, X., Chen, X., Badmaev, V., Ho, C.T., and Sang, S. (2010). Structural identification of mouse urinary metabolites of pterostilbene using liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 24: 1770-1778.
  • Shen, D., Pan, M.H., Wu, Q.L., Park, C.H., Juliani, H.R., Ho, C.T., and Simon, J.E. (2010). An LC/MS method on the simultaneous quantitation of the anti-inflammatory constituents in oregano (Origanum spp.). Journal of Agricultural and Food Chemistry, 58: 7119-7125.
  • Jan, K.C., Ku, K.L., Chu, Y.H., Hwang, L.S., and Ho, C.T. (2010). Tissue Distribution and elimination of estrogenic and anti-inflammatory catechol metabolites from sesaminol triglucoside in rats. Journal of Agricultural and Food Chemistry, 58: 7693-7700.


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

Outputs
OUTPUTS: We found that 6-shogaol strongly suppressed lipopolysaccharide-induced up-expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. We further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrated that topical application of 6-shogaol more effectively inhibited TPA-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB subunits. 6-Shogaol also reduced TPA-induced phosphorylation of IkappaB and p65, and caused subsequent degradation of IkappaB. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), JNK1/2, and phosphatidylinositol 3-kinase (PI3K)/Akt, which are upstream of NFkappaB and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. Presented data for the first time reveal that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. Pterostilbene (PS), a natural dimethylated analogue of resveratrol, is known to have diverse pharmacologic activities including anticancer, anti-inflammation, antioxidant, apoptosis, antiproliferation and analgesic potential. However, the effects of pterostilbene in preventing invasion of cancer cells have not been studied. Here we report our finding that pterostilbene significantly suppressed TPA-induced invasion, migration and metastasis of human hepatoma cells (HepG2 cells). Increase in the enzyme activity, protein and messenger RNA levels of matrix metalloproteinase (MMP)-9 were observed in TPA-treated HepG2 cells, and these were blocked by pterostilbene. In addition, pterostilbene can inhibit TPA-induced expression of VEGF, EGF and EGFR. Transient transfection experiments also showed that pterostilbene strongly inhibited TPA-stimulated nuclear factor-kappa B and activator protein-1 (AP-1)-dependent transcriptional activity in HepG2 cells. Moreover, pterostilbene can suppress TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinases 1/2 (JNK1/2), and phosphatidylinositol 3-kinase (PI3K)/Akt, and PKC which are upstream of NFkappaB and AP-1. Significant therapeutic effects were further demonstrated in vivo by treating nude mice with pterostilbene (50 mg/kg and 250 mg/kg i.p.) after inoculation with HepG2 cells into the tail vein. Presented data reveals that pterostilbene is a novel, effective, anti-metastatic agent that functions by downregulating MMP-9 gene expression. PARTICIPANTS: Jong Han Lee, a graudate student worked on this project. Mr. Lee has obtained his Ph.D degree in January 2010. TARGET AUDIENCES: We have published several peer reviewed papers in journals, and presented our research in the annual meeting of the American Chemical Sociery as well as Interantioanl Society of Nutraceuticals and Functional Foods. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
The shogaols are the dehydration products of related gingerols during storage or thermal processing. It has been reported that the ratio of [6]-gingerol to [6]-shogaol was about 10:1 in fresh ginger and about 1:1 in dried ginger. Therefore, the contents of shogaols and gingerols in ginger preparations can vary greatly. This may have contributed to the inconsistency on published effects of ginger preparations. Thus, ginger extract with high levels of shogaols such as extract from dry ginger may have stronger cancer preventive effect than ginger extract with high levels of gingerols, such as extract from fresh ginger. It is important to identify the bioactive components from ginger and standardize the products for use in future laboratory studies and clinical trials. The development of a standardized and a more active ginger extract preparation will facilitate future pre-clinical and clinical studies on the health benefit of ginger extracts.

Publications

  • Yeh, L.T., Charles, A.L., Ho, C.-T., Huang, T.C. A novel bread making process using salt-stressed baker's yeast. Journal of Food Science 2009, 74, S399-S402.
  • Wang, Y., Ho, C.-T. Polyphenolic chemistry of tea and coffee: A century of progress. Journal of Agricultural and Food Chemistry 2009, 57, 8109-8114.
  • Huang, Y.W., Liu, Y., Dushenkov, S., Ho, C.-T., Huang, M.T. Anti-obesity of epigallocatechin gallate, orange peel extract, black tea extract, caffeine and their combinations in a mouse model. Journal of Functional Foods 2009, 1, 304-310.
  • Cheng, K.W., Yang, R.Y., Tsou, S.C.S., Lo, C.S.C., Ho, C.-T., Lee, T.C., Wang, M. Analysis of antioxidant activity and antioxidant constituents of Chinese toon. Journal of Functional Foods 2009, 1, 253-259.
  • Jan, K.C., Hwang, L.S., Ho, C.-T. Biotransformation of sesaminol triglucoside to mammalian lignans by intestinal microbiota. Journal of Agricultural and Food Chemistry 2009, 57, 6101-6106
  • Jan, K.C., Hwang, L.S., Ho, C.-T. Tissue Distribution and elimination of sesaminol triglucoside and its metabolites in rat. Molecular Nutrition & Food Research 2009, 53, 815-825.
  • Pan, M.H., Chiou, Y.S., Chen, W.J., Wang, J.M., Badmaev, V., Ho, C.-T. Pterostilbene inhibited tumor invasion via suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Carcinogenesis 2009, 30, 1234-1242.
  • Sergeev, I.N., Li, S., Ho, C.-T., Rawson, N.E., Dushenkov, S. Polymethoxyflavones activate Ca2+-dependent apoptotic targets in adipocytes. Journal of Agricultural and Food Chemistry 2009, 57, 5771-5776.
  • Cheng, K.W., Wong, C.C., Chao, J., Lo, C., Chen, F., Chu, I.K., Che, C.M., Ho, C.-T., Wang, M. Inhibition of mutagenic PhIP formation by epigallocatechin gallate via scavenging of phenylacetaldehyde. Molecular Nutrition & Food Research 2009, 53, 716-725.
  • Pan, M.H., Lai, C.S., Deshenkov, S., Ho, C.-T. Modulation of inflammatory genes by natural dietary bioactive compounds. Journal of Agricultural and Food Chemistry 2009, 57, 4467-4477.
  • Lai, C.S., Wang, Y.J., Lee, J., Ho, C.-T., Pan, M.H. Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through down-regulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways. Journal of Agricultural and Food Chemistry 2009, 57, 10990-10998..
  • Pan, M.H., Yang, J.R., Tsai, M.L., Sang, S., Ho, C.-T. Anti-inflammatory effect of Momordica grosvenori Swingle extract through suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Journal of Functional Foods 2009, 1, 145-152.
  • Wang, Y., Ho, C.-T. Metabolism of flavonoids. In Food Factors for Health Promotion, Edited by Toshikazu Yoshikawa, S. Karger AG; Forum of Nutrition 2009, 61, 64-74.
  • Wu, H., Dushenkov, S., Ho, C.-T., Sang, S. Novel acetylated flavonoid glycosides from the leaves of Allium ursinum. Food Chemistry 2009, 115, 592-595.
  • Yang, Y.T., Weng, C.J., Ho, C.-T., Yen, G.C. Resveratrol analog - 3,5,4'-trimethoxy-trans-stilbene inhibits invasion of human lung adenocarcinoma cells by suppressing the MAPK pathway and decreasing matrix metalloproteinase-2 expression. Molecular Nutrition & Food Research 2009, 53, 407-416.
  • Xiao, H., Yang, C.S., Li, S., Jin, H., Ho, C.-T., Patel, T. Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung carcinoma cells by apoptosis. Molecular Nutrition & Food Research 2009, 53, 398-406.
  • Zhu, Q., Liang, C.P., Cheng, K.W., Peng, X., Lo, C.Y., Shahidi, F., Chen, F., Ho, C.-T., Wang, M. Trapping effects of green and black tea extracts on peroxidation-derived carbonyl substances of seal blubber oil. Journal of Agricultural and Food Chemistry 2009, 57, 1065-1069.
  • Weng, C.J., Yang, Y.T., Ho, C.-T., Yen, G.C. Mechanisms of apoptotic effects induced by resveratrol, dibenzoylmethane, and their analogs on human lung carcinoma cells. Journal of Agricultural and Food Chemistry 2009, 57, 5235-5243.
  • Li, S., Pan, M.H., Lo, C.Y., Tan, D., Wang, Y., Shahidi, F., Ho, C.-T. Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones. Journal of Functional Foods 2009, 1, 2-12.


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

Outputs
OUTPUTS: Reactive dicarbonyl species, such as methylglyoxal (MGO) and glyoxal (GO), have received extensive attention recently due to their high reactivity and ability to form advanced glycation end products (AGEs) with biological substances such as proteins, phospholipids, and DNA. In the present study, we found that both phloretin and its glucoside, phloridzin, the major bioactive apple polyphenols, could efficiently trap reactive MGO or GO to form mono- and di- MGO or GO adducts under physiological conditions. More than 80% MGO was trapped within ten minutes and 68% GO was trapped within 24 h by phloretin. Phloridzin also had strong trapping efficiency by quenching more than 70% MGO and 60% GO within 24 h. The products formed from phloretin (or phloridzin) and MGO (or GO), combined at different ratios, were analyzed using LC/MS. Our LC/MS and NMR data showed that positions 3 and 5 of the phloretin or phloridzin A-ring were the major active sites for trapping reactive dicarbonyl species. Our results suggest that dietary flavonoids that have the same A-ring structure as phloretin may have the potential to trap reactive dicarbonyl species and therefore inhibit the formation of AGEs. We continue our study on the anti-inflammatory and anticarcinogenic propeties of polymethoxyflavones from sweet orange peel. We previously reported that 3',4'-didemethylnobiletin (DDMN) is the major metabolite of nobiletin in mouse urine. In this study, we examined DDMN's molecular mechanism of action and its anti-inflammatory and anti-tumor properties. We demonstrated that topical application of DDMN effectively inhibited O-tetradecanoylphorbol-13-acetate (TPA)-stimulated transcription nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and ornithine decarboxylase (ODC) mRNA and protein expression in mouse skin. Pretreatment with DDMN has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB subunit. DDMN also reduced DNA binding by blocking phosphorylation of IkappaB and p65, and caused subsequent degradation of IkappaB. DDMN inhibited TPA-induced phosphorylation and nuclear translocation of the signal transducer and activator of transcription-3 (STAT3). Moreover, DDMN suppressed TPA-induced activation of extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and PKC which are upstream of NFkappaB and AP-1. We also found that DDMN significantly inhibited TPA-induced mouse skin inflammation by decreasing inflammatory parameters. Furthermore, DDMN significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 weeks. It is suggested that DDMN is a novel functional agent capable of preventing inflammation-associated tumorigenesis. PARTICIPANTS: Collaborators: Professor Min-Hsiung Pan: Department of Seafood Science, National Kaohsiung Marine University, Kaohsiung 811, Taiwan Professor Shengmin Sang: Nutrition Research Program, University of North Carolina Nutrition Center, North Carolina Research Campus, Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 500 Laureate Way, Kannapolis, NC 28081 TARGET AUDIENCES: Presented at the annual meeting of the American Chemical Society. PROJECT MODIFICATIONS: Not relevant to this project.

Impacts
Reactive carbonyl species have been shown to be one of the major factors for diabetic complications. Our previous report that carbonated beverages contain high levels of methylglyoxal and glyoxal, and may have damage to public health. We have observed that tea catechins have stronge ability to trap reactive carbonyl species. In this report period, we further discovered that apple polyphenols also have similar reactive carbonyl species trapping ability. Our discovery should have publics a way to reduce the risk of diabetes or control the diabetic complications through healthy diet. We continue research on the health beneficial properties of polymethoxyflavones from sweet orange peel, and many compounds, particularly the hydroxylated ploymethoxyflavones have potent anti-inflammatory and anticarcinogenic properties. This discovery may help orange growers to enhance the value-added to this US important fruits. It may also have impact to public health.

Publications

  • Xiao, H., Yang, C.S., Li, S., Jin, H., Ho, C.-T., Patel, T. (2008). Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel inhibit growth of human lung carcinoma cells by apoptosis. Molecular Nutrition & Food Research, DOI: 10.1002/mnfr.200800057.
  • Jan, K.C., Ho, C.-T., Hwang, L.S. (2008). Bioavailability and tissue distribution of sesamol in rat. Journal of Agricultural and Food Chemistry, 56: 7032-7037.
  • Yang, Y.T., Weng, C.J., Ho, C.-T., Yen, G.C.(2008). Resveratrol analog - 3,5,4'-trimethoxy-trans-stilbene inhibits invasion of human lung adenocarcinoma cells by suppressing the MAPK pathway and decreasing matrix metalloproteinase-2 expression. Molecular Nutrition & Food Research, DOI: 10.1002/mnfr.200800123.
  • Pan, M.H., Hsieh, M.C., Hsu, P.C., Ho, S.Y., Lai, C.S., Wu, H., Sang, S., Ho, C.-T. (2008). 6-Shogaol suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Molecular Nutrition & Food Research, 52: 1467-1477. Lai, C.S., Li, S., Chai, C.Y., Lo, C.Y., Denshenkov, S., Ho, C.-T., Pan, M.H., Wang, Y.J. (2008). Anti-inflammatory and anti-tumor promotional effects of a novel urinary metabolite, 3',4'-didemethylnobiletin, derived from nobiletin. Carcinogenesis, 29, 2415-2424.
  • Pan, M.H., Ho, C.-T. (2008). Chemopreventive effects of natural dietary compounds on cancer development. Chemical Society Reviews, 37: 2558-2574.
  • Shao, X., Bai, N., He, K., Ho, C.-T., Yang, C.S., Sang, S. (2008). Apple polyphenols, phloretin and phloridzin: New trapping agents of reactive dicarbonyl species. Chemical Research in Toxicology, 21: 2042-2050.
  • Eguchi, A., Murakami, A., Li, S., Ho, C.-T., Ohigashi, H. (2008). Suppressive effects of demethylated metabolites of nobiletin on phorbol ester-induced expression of scavenger receptor genes in THP-1 human monocytic cells. Biofactors, 31: 107-116.
  • Pan, M.H., Hsieh, M.C., Kuo, J.M., Lai, C.S., Hou, W., Sang, S., Ho, C.-T. (2008). 6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression. Molecular Nutrition & Food Research, 52: 527-537.
  • Tan, D., Wang, Y., Lo, C.Y., Sang, Sh., Ho, C.-T. (2008). Methylglyoxal: Its presence in beverages and potential scavengers. In The Maillard Reaction: Recent Advances in Food and Biomedical Sciences, Edited by Erwin Schleicher; Veronika Somoza; Peter Schieberle; Annals of the New York Academy of Sciences, 1126: 72-75.
  • Peng, X., Cheng, K.W., Ma, J., Chen, B., Ho, C.-T., Chen, F., Wang, M. (2008). Cinnamon bark proanthocyanidins as reactive carbonyl scavengers to prevent the formation of advanced glycation endproducts. Journal of Agricultural and Food Chemistry, 56: 1907-1911. Pan, M.H., Gao, J.H., Lai, C.S., Wang, Y.J., Chen, W.M., Lo, C.Y., Wang, M., Dushenkov, S., Ho, C.-T. (2008). Antitumor activity of 3,5,4'-trimethoxystilbene in COLO 205 cells and xenografts in SCID mice. Molecular Carcinogenesis, 47: 184-196.
  • Tan, D., Wang, Y., Lo, C.Y., Ho, C.-T. (2008). Methylglyoxal: its presence and potential scavengers. Asian Pacific Journal of Clinical Nutrition, 17(S1): 257-260. Pan, M.H., Ghai, G., Ho, C.-T. (2008). Food bioactives, apoptosis and cancer. Molecular Nutrition & Food Research, 52: 43-52. Lin, C.C., Tsai, Y.L., Ho, C.-T., Teng, S.C. (2008). Determination of the differential estrogenicity of isoflavonoids by E2-ER-ERE-dependent gene expression in recombinant yeast and MCF-7 human breast cancer cells. Food Chemistry, 108: 719-726,
  • Wang, Z., Li, S., Ferguson, S., Goodnow, R., Ho, C.-T. (2008). Validated reversed phase LC method for quantitative analysis of polymethoxyflavones in citrus peel extract. Journal of Separation Science, 31: 30-37.
  • Lo, C.Y., Li, S., Wang, Y., Tan, D., Pan, M.H., Sang, S., Ho, C.-T. (2008). Reactive dicarbonyl compounds and 5-(hydroxymethyl)-2-furfural in carbonated beverages containing high fructose corn syrup. Food Chemistry, 107: 1099-1105.
  • Shibamoto, T., Kanazawa, K., Shahidi, F., Ho, C.-T. (Eds.). (2008). Functional Foods and Health, ACS Symposium Series 993, American Chemical Society, Washington, D.C., 514 pages.
  • Ho, C.-T., Simon, J.E., Shahidi, F., Shao, Y. (Editors). (2008). Dietary Supplements. ACS Symposium Series No. 987, American Chemical Society, Washington, D.C., 335 pages.
  • Ho, C.-T., Lin, J.K., Shahidi, F. (Editors.). (2008). Tea and Tea Products: Chemistry and Health Promoting Properties. CRC Press, Taylor & Francis Group, Boca Raton, FL., 305 pages.
  • Pan, M.H., Chang, Y.H., Tsai, M.L., Lai, C.S., Ho, S.Y., Badmaev, V., Ho, C.-T. (2008). Pterostilbene suppressed lipopolysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages. Journal of Agricultural and Food Chemistry, 56: 7502-7509.


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

Outputs
OUTPUTS: 1. Orangize a symposium on "Food Bioactives and Nutraceuticals: Production, Chemistry, Analysis and Health Effects" during the 234th ACS Fall Meeting held on August 19-23, 2007 in Boston MA. 2. Three patents: "Extracts of orange peel for prevention and treatment of cancer. US Patent 7,201,928"; "Black tea extract for prevention of disease. US Patent 7,238,376" and "Benzotropolone derivatives and modulation of inflammatory response. US Patent 7,288,680" have been granted in 2001. 3. A paper "Reactive carbonyl species and tea components: Dicarbonyl compounds and 5-(hydroxymethyl)-2-furfural in beverages containing high fructose corn syrup" was presented at the ACS Meeting on August 22, 2007 in Boston, this paper has received massive media coverages. PARTICIPANTS: Indivuals worked on the project: Di Tan (grauduate student), Yu wang (graudate student) Collaborators: Dr. Shengmin Sang (Laboratory of Cancer Research, Rutgers Uniberisty); Professor Min-Hsiung Pan (National Kaohsiung Marine University, Taiwan)

Impacts
Nonenzymic glycation, also known as Maillard reaction, is a complex series of reactions between reducing sugars and amino compounds. Previous studies have demonstrated that reactive dicarbonyl compounds [e.g., methylglyoxal (MG) and glyoxal (GO)] formed as intermediate products of Maillard reaction irreversibly and progressively modified proteins over time and yielded advanced glycation end products (AGEs), which are thought to contribute to the development of diabetes mellitus and its complications. Several studies have shown that higher levels of MG are present in the plasma of diabetic patients than in healthy people. Thus decreasing the levels of MG and GO will be an effective approach to reduce the formation of AGEs and the development of diabetic complications. Here, we briefly describe our effort in searching for non- or less-toxic trapping agents of reactive dicarbonyl species from dietary sources. In addition, we have discovered that commercial beverages contain extremely high levels of MG. The potential hazardous effects of dietary MG on humans remain to be explored. Ginger, the rhizome of Zingiber officinale, is a traditional medicine with anti-inflammatory and anti-carcinogenic properties. We investigated the inhibitory effects of 6-shogaol and a related compound, 6-gingerol, on the induction of NO synthase (NOS) and cyclooxygenase-2 (COX-2) in murine RAW 264.7 cells activated with lipopolysaccharide (LPS). In comparison with two compounds tested, 6-shogaol markedly and actively inhibited the transcriptional activation of iNOS and COX-2. Western blotting and reverse transcription-polymerase chain reaction (PCR) analyses demonstrated that 6-shogaol significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-inducted macrophages. Treatment with 6-shogaol resulted in the reduction of LPS-induced nuclear translocation of nuclear factor-kappa B (NFkappaB) subunit and the dependent transcriptional activity of NFkappaB. Transient transfection experiments using NFkappaB reporter constructs indicated that 6-shogaol inhibits the transcriptional activity of NFkappaB in LPS-stimulated mouse macrophages. We further investigated the roles of tyrosine kinase, phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-induced macrophages. We found that 6-shogaol also inhibited LPS induced activation of PI3K/Akt and extracellular signal-regulated kinase 1/2, but not p38 MAPK. Taken together, these results show that 6-shogaol down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFkappaB by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that 6-shogaol is a functionally novel agent capable of preventing inflammation. Resource from this project has provided fund to partially help student's stipend and chemicals to complete this work.

Publications

  • Li, S., Lambros, T., Wang, Z., Goodnow, R., and Ho, C.-T. (2007). Efficient and scalable method in isolation of polymethoxyflavones from orange peel extract by supercritical fluid chromatography. Journal of Chromatography B, 846: 291-297.
  • Pan, M.H., Chiou, Y.S., Cheng, A.C., Bai, N., Lo, C.Y., Tan, D., and Ho, C.-T. (2007). Involvement of MAPK, Bcl-2 family, cytochrome c, and caspases in induction of apoptosis by 1,6-O,O-diacetylbritannilactone in human leukemia cells. Molecular Nutrition & Food Research, 51: 229-238.
  • Weng, M.S., Ho, C.-T., Ho, Y.S., and Lin, J.K. (2007). Theanaphthoquinone inhibits fatty acid synthase expression in EGF-stimulated human breast cancer cells via the regulation of EGFR/ErbB-2 signaling. Toxicology and Applied Pharmacology, 218: 107-118.
  • Huang, T.C., Fu, H.Y., Ho, C.-T., Tan, D., Huang, Y.T., and Pan, M.H. (2007). Induction of apoptosis by cinnamaldehyde from indigenous cinnamon Cinnamomum osmophloeum Kaneh through reactive oxygen species production, glutathione depletion, and caspase activation in human leukemia K562 cells. Food Chemistry, 103: 434-443.
  • Hong, J., Kwon, S.J., Sang, S., Ju, J., Zhou, J., Ho, C.-T., Huang, M.T., and Yang, C.S. (2007). Effects of garcinol and its derivatives on intestinal cell growth: Inhibitory effects and antioxidation-dependent growth stimulatory effects. Free Radical Biology & Medicine, 42: 1211-1221.
  • Li, S., Pan, M.H., Lai, C.S., Lo, C.Y., Dushenkov, S., and Ho, C.-T. (2007). Isolation and synthesis of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorganic and Medicinal Chemistry, 15: 3381-3389.
  • Lv, L., Gu, X., Tang, J., and Ho, C.-T. (2007). Antioxidant activity of stilbene glycoside from Polygonum multiflorum Thunb in vivo. Food Chemistry, 104: 1678-1681.
  • Pan, M.H., Lai, Y.S., Lai, C.S., Wang, Y.J., Li, S., Lo, C.Y., Dushenkov, S., and Ho, C.-T. (2007). 5-Hydroxy-3,6,7,8,3',4'-hexamethoxyflavone induces apoptosis through reactive oxygen species production, growth arrest and DNA damage-inducible gene 153 expression, and caspases activation in human leukemia cells. Journal of Agricultural and Food Chemistry, 55: 5081-5091.
  • Sang, S., Yang, I., Buckley, B., Ho, C.-T., and Yang, C.S. (2007). Autoxidative quinone formation in vitro and metabolite formation in vivo from tea polyphenol (-)-epigallocatechin-3-gallate: Studied by real-time mass scanning combined with tandem mass ion mapping. Free Radical Biology & Medicine, 43: 362-371.
  • Li, S., Sang, S., Pan, M.H., Lai, C.S., Lo, C.Y., Yang, C.S. and Ho, C.-T. (2007). Anti-inflammatory property of the urinary metabolites of nobiletin in mouse. Bioorganic and Medicinal Chemistry Letters, 17: 5177-5181.
  • Pan, M.H.,; Chang, Y.H., Badmaev, V., Nagabhushanam, K., and Ho, C.-T. (2007). Pterostilbene induces apoptosis and cell cycle arrest in human gastric carcinoma cells. Journal of Agricultural and Food Chemistry, 55: 7777-7785.
  • Lai, C.S., Li, S., Chai, C.Y., Lo, C.Y., Ho, C.-T., Wang, Y.J., and Pan, M.H. (2007). Inhibitory effect of citrus 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone on 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumor promotion in mice. Carcinogenesis, 28: 2581-2588.
  • Sang, S., Shao, X., Bai, N., Lo, C.Y., Yang, C.S. and Ho, C.-T. (2007). Tea polyphenol (-)-epigallocatechin-3-gallate: A new trapping agent of reactive dicarbonyl species. Chemical Research in Toxicology, 20, 1862-1870.


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

Outputs
The carbonyl stress that leads to the formation of advanced glycation end products (AGEs) in diabetes mellitus has drawn much attention recently. Reactive alpha-dicarbonyl compounds, such as glyoxal (GO) and methylglyoxal (MGO), have been shown to be a high potential glycation agent in vitro and in vivo. In this study, epicatechins in green tea and theaflavins in black tea were found to be able to reduce the concentration of methylglyoxal in physiological phosphate buffer conditions. Modified methylglyoxal derivatization for GC/FID method in quantification was systematically conducted. In molar ratio of 3 (MGO:polyphenol), theaflavin-3,3′-digallate (TF3) in theaflavins and (-)-epigallocatechin (EGC) in epicatechins showed the highest MGO reduction at 66.65% and 45.74%, respectively, after 1 hour of incubation. In kinetic study (molar ratio of MGO: polyphenol = 1:1), rapid MGO reduction occurred within 10 minutes. Identities of primary adducts between (-)-epigallocatechin gallate (EGCG) and MGO were determined. Newly generated stereoisomers at the C8 position of EGCG A-ring were isolated with a chiral column and structurally confirmed by 2-D NMR analyses.

Impacts
Our identification of tea polyphenols ability to trap reactive carbonyl species under physiological conditions may provide a dietary means for diabetic patients to delay or manage the complication of their disease.

Publications

  • Wei, G.J. and Ho, C.-T. 2006. A stable quinone identified in the reaction of carnosol, a major antioxidant in rosemary, with 2,2-diphenyl-1-picrylhydrazyl radical. Food Chem. 96: 471-476.
  • Lin, C.C.; Tsai, Y.L., Huang, M.T., Lu, Y.P., Ho, C.-T., Tseng, S.F. and Teng, S.C. 2006. Inhibition of estradiol-induced mammary proliferation by dibenzoylmethane through the E2-ER-ERE-dependent pathway. Carcinogenesis 27: 131-136.
  • Li, S., Yu, H. and Ho, C.-T. 2006. Nobiletin: Efficient and large quantity isolation from orange peel extract. Biomed. Chromatogr. 20: 133-138.
  • Ueno, T., Kiyohara, S., Ho, C.-T. an Masuda, H. 2006. Potent inhibitory effects of black tea theaflavins on off-odor formation from citral. J. Agric. Food Chem. 54: 3055-3061.
  • Bai, N., Lai, C.S., He, K., Zhou, Z., Zhang, L., Quan, Z., Zhu, N., Zheng, Q.Y., Pan, M.H. and Ho, C.-T. 2006. Sesquiterpene lactones from Inula Britannica and their cytotoxic and apoptotic effects on human cancer cell lines. J. Nat. Prod. 69: 531-535. Şensoy, ĺ., Rosen, R.T., Ho, C.-T. and Karwe, M.V. 2006. Effect of processing on buckwheat phenolics and antioxidant activity. Food Chem. 99: 388-393.
  • Li-Shuang, L.V., Gu, X., Ho, C.-T. and Tang, J. 2006. Stilbene glycosides from the roots of Polygonum multiflorum Thunb and their in vitro antioxidant activities. J. Food Lipids 13: 131-144.
  • Li, S., Lo, C.Y. and Ho, C.-T. 2006. Hydroxylated polymethoxyflavones and methylated flavonoids in sweet orange (Citrus sinensis) peel. J. Agric. Food Chem. 54: 4176-4185.
  • Hong, J., Sang, S., Park, H.J., Kwon, S.J., Suh, N., Huang, M.T., Ho, C.-T. and Yang, C.S. 2006. Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives. Carcinogenesis 27: 278-286.
  • Huang, M.T., Liu, Y., Ramji, D., Lo, C.Y., Ghai, G., Dushenkov, S. and Ho, C.-T. 2006. Inhibitory effect of black tea theaflavin derivatives on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and arachidonic acid metabolism in mouse ears. Mol. Nutr. Food Res. 50: 115-122.
  • Mizuno, H., Cho, Y.Y., Zhu, F., Ma, W.Y., Bode, A.M., Yang, C.S., Ho, C.-T. and Dong, Z. 2006. Theaflavin-3,3′-digallate induces epidermal growth factor receptor downregulation. Molecular Carcinogenesis 45: 204-212.
  • Li, S., Wang, Z., Sang, S., Huang, M.T. and Ho, C.-T. 2006. Identification of nobiletin metabolites in mouse urine. Mol. Nutr. Food Res. 50: 291-299.
  • Cheng, A.C., Huang, T.C., Lai, C.S., Kuo, J.M., Huang, Y.T., Lo, C.Y., Ho, C.-T. and Pan, M.H. 2006. Pyrrolidine dithiocarbamate inhibition of luteolin-induced apoptosis through up-regulated phosphorylation of Akt and caspase-9 in human leukemia HL-60 cells. J. Agric. Food Chem. 54, 4215-4221. Jun, M., Jeong, W.S. and Ho, C.-T. 2006. Health promoting properties of natural flavor substances. Food Sci. Biotechnol. 15: 329-338.
  • Li, J., Wang, T., Wu, H., Ho, C.-T. and Weng, X. 2006. 1,1-Di-(2′,5′-dihydroxy-4′-tert-butylphenyl)ethane: A novel antioxidant. J. Food Lipids 13: 331-340.
  • Wang, Z., Li, S., Jonca, M., Lambros, T., Ferguson, S., Goodnow, R. and Ho, C.-T. 2006. Comparison of supercritical fluid chromatography and liquid chromatography for the separation of urinary metabolites of nobiletin with chiral and non-chiral stationary phases. Biomed. Chromatogr. 20: 1206-1215.
  • Lambert, J.D., Sang, S., Hong, J., Kwon, S.J., Lee, M.J., Ho, C.-T. and Yang, C.S. 2006. Peracetylation as a means of enhancing in vitro bioactivity and bioavailability of epigallocatechin-3-gallate. Drug Met. Disposition 34: 2111-2116.
  • Lo, C.Y., Li, S., Tan, D., Pan, M.H., Sang, S. and Ho, C.-T. 2006. Trapping reactions of reactive carbonyl species with tea polyphenols in simulated physiological conditions. Mol. Nutr. Food Res. 50: 1118-1128.
  • Pan, M.H., Huang, Y.T., Ho, C.-T., Chang, C.I, Hsu, P.C. and Pan, B.S. 2006. Induction of apoptosis by Meretrix lusoria through reactive oxygen species production, GSH depletion, and caspase activation in human leukemia cells. Life Sci. 79: 1140-1152.
  • Pan, M.H., Lai, C.S., Wang, Y.J. and Ho, C.-T. 2006. Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice. Biochem. Phamacol. 72: 1293-1303.


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

Outputs
It is too early in the life of the project to report on its progress.

Impacts
The identification of the active antioxidants and health-promoting compounds, theaflavins in black tea will allow the researchers and industry to optimize the processing technology to maximize the content of these theaflavins in black tea products. It will have direct impact to the health of consumers. It will also improve the market value of black teas.

Publications

  • No publications reported this period


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

Outputs
Black tea contains two major groups of pigments, theaflavins (TFs) and thearubigins (TRs). TFs contain a bis-flavan substituted 1,2-dihydroxy-3,4-benzotropolone moiety. Unlike the TFs, TRs have not yet been characterized. We have studied the structure of TFs and TRs using delayed pulsed ion extraction of ions generated via the Matrix Assisted Laser Desorption Ionization technique, on line with a Linear Time of Flight mass spectrometer. Spectra of standard TFs show not only pseudomolecular ions but also ions resulting from fragmentation. The analysis of MALDI-TOF spectra of black tea fractions shows the structure of some TRs, which are similar to those of TFs because the same loss of mass is observed. In the course of studies on the oxidation mechanism of tea polyphenols, especially the formation of thearubigins, a method combining the enzymatic synthesis and LC/ESI-MS/MS analysis was developed to search for new higher molecular weight polymers from black tea. Three new dibenzotropolones, theadibenzotropolone A, B and C, together with one new tribenzotropolone, theatribenzotropolone A, were formed by the reaction of theaflavins and tea catechins with horseradish peroxidase in the presence of H2O2. The existence of these compounds in black tea was characterized by LC/ESI-MS/MS. Theadibenzotropolone A and B were the first benzotropolone type trimers of catechins found in the black tea extract. The observation that galloyl ester groups of theaflavins can be oxidized to form di- or tri-benzotropolone skeletons strongly implied that this type of oxidation is an important pathway to extend the molecular size of thearubigins. A number of in-vitro and in-vivo studies have demonstrated that black tea polyphenols have significant biological activities, including antioxidant, anti-inflammatory and anti-cancer activity. The theaflavins have received attention as one of responsible components for biological activities of black tea. However, little information is available for the biological activity of individual theaflavins and minor components in black tea. Theaflavins and epitheaflavic acid were synthesized from their parent flavan-3-ols catechins using an enzymatic oxidation method and employing crude polyphenol oxidase from banana fruit. The peroxyl radical scavenging activities of theaflavins and epitheaflavic acids were measured using modified ORAC method. The results indicated that theaflavins have higher peroxyl radical scavenging activity than EGCG. The hierarchy of radical scavenging activity of theaflavins, epitheaflavic acid and related compounds were in the order of theaflavin-3,3'-digallate ≈ theflavin-3-gallate ≥ theaflavin-3'-gallate ≥ theaflavin > epitheaflavic acid > EGCG > purpurogallin. Stability of theaflavin was studied in varying pH solutions: simulated gastric juice and buffer solution of pH 5.5, pH 7.4, and pH 8.5. The results indicated that theaflavin is unstable in alkaline condition, while it was stable in acidic condition.

Impacts
The identification of the active antioxidants and health-promoting compounds, theaflavins in black tea will allow the researchers and industry to optimize the processing technology to maximize the content of these theaflavins in black tea products. It will have direct impact to the health of consumers. It will also improve the market value of black teas.

Publications

  • Liao, C.H., Sang, S., Liang, Y.C., Ho, C.-T. and Lin, J.K. 2004, Suppression of inducible nitric oxide synthase and cyclooxygenase-2 in down-regulating nuclear factor-kappa B pathway by garcinol. Mol. Carcinogenesis 41: 140-149.
  • Huang, M.-T., Ghai, G. and Ho, C.-T. 2004, Inflammatory process and molecular targets for anti-inflammatory nutraceuticals. Comp. Rev. Food Sci. Food Safety 3: 127-139.
  • Sang, S., Yang, C.S. and Ho, C.-T. 2004, Peroxidase-mediated oxidation of catechins. Phytochemistry Reviews 3: 229-241.
  • Wei, G.J., Huang, T.C., Huang, A.S. and Ho, C.-T. 2004, Flavor compounds of noni fruit (Morinda citrifolia L.) juice. In Nutraceutical Beverages: Chemistry, Nutrition, and Health Effects. Edited by F. Shahidi and D.K. Weerasinghe, ACS Symp. Ser. 871, American Chemical Society: Washington, D.C., pp. 52−61.
  • Sang, S., Lambert, J.D., Tian, S., Hong, J., Hou, Z., Rya, J.H., Stark, R.E., Rosen, R.T., Huang, M.T., Yang, C.S. and Ho, C.-T. 2004, Enzymatic synthesis of tea theaflavin derivatives and their anti-inflammatory and cytotoxic activities. Bioorg. Med. Chem. 12: 459-467.
  • Lee, M.J., Lambert, J.D., Prabhu, S., Meng, X., Lu, H., Maliakal, P., Ho, C.-T. and Yang, C.S. 2004, Delivery of tea polyphenols to the oral cavity by green tea leaves and black tea extract. Cancer Epidemiology, Biomarkers & Prevention 13: 132-137.
  • Liu, S., Liu, H., Yan, W., Zhang, L., Bai, N. and Ho, C.-T. 2004, Studies on 1-O-acetylbritannilactone and its derivative, (2-O-butyloxime-3-phenyl) propionyl 1-O-acetylbritannilactone ester. Bioorg. Med. Chem. Lett. 14: 1101-1104.
  • Menet, M.C., Sang, S., Yang, C.S., Ho, C.-T. and Rosen, R.T. 2004, Analysis of theaflavins and thearubigins from black tea extract by MALDI-TOF mass spectrometry. J. Agric. Food Chem. 52: 2455−2461.
  • Huang, T.C., Ho, C.-T. and Fu, H.Y. 2004, Inhibition of lipid oxidation in pork bundles processing by superheated steam frying. J. Agric. Food Chem. 52: 2924−2928.
  • Sang, S., Tian, S., Stark, R.E., Yang, C.S. and Ho, C.-T. 2004, New dibenzotropolone derivatives characterized from black tea using LC/MS/MS. Bioorg. Med. Chem. 12: 3009-3017.
  • Lee, H.H., Ho, C.-T. and Lin, J.K. 2004, Theaflavin-3,3'-digallate and penta-O-galloyl-beta-D-glucose inhibit rat liver microsomal 5-alpha-reductase activity and the expression of androgene receptor in LNCaP prostate cancer cells. Carcinogenesis 25: 1109-1118.
  • Jhoo, J.W., Sang, S., Wei, G.J., Lee, T.C., Rosen, R.T. and Ho, C.-T. 2004, Enzymatic synthesis of theaflavins and epitheaflavic acid from tea catechins and their antioxidant activity. J. Food Lipids 11: 89-103.
  • Ueno, T, Masuda, H. and Ho, C.-T. 2004, Formation pathways of p-methylacetophenone from citral via a tert-alkoxy radical intermediate. J. Agric. Food Chem. 52: 5677-5684.
  • Liang, C.P., Wang, M., Simon, J.E. and Ho, C.-T. 2004, Antioxidant activity of plant extracts on the inhibition of citral off-odor formation. Mol. Nutr. Food Res. 48: 308-317.


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

Outputs
A number of in-vitro and in-vivo studies have demonstrated that black tea polyphenols have significant biological activities, including antioxidant, anti-inflammatory and anti-cancer activity. The theaflavins have received attention as one of responsible components for biological activities of black tea. However, little information is available for the biological activity of individual theaflavins and minor components in black tea. In the presented study, theaflavins and epitheaflavic acid were synthesized from their parent flavan-3-ols catechins using an enzymatic oxidation method and employing crude polyphenol oxidase from banana fruit. The compounds were isolated using column chromatographic methods, and their structures were confirmed by 1H-NMR and APCI-MS. The peroxyl radical scavenging activities of theaflavins and epitheaflavic acids were measured using modified ORAC method. The results indicated that theaflavins have higher peroxyl radical scavenging activity than EGCG. The hierarchy of radical scavenging activity of theaflavins, epitheaflavic acid and related compounds were in the order of theaflavin-3,3'-digallate = theflavin-3-gallate ≥ theaflavin-3'-gallate ≥ theaflavin > epitheaflavic acid > EGCG > purpurogallin. Since the uniqueness of theaflavins is their prexence of benzotrolone unit. Several derivatives based on a benzotropolone skeleton have been prepared by the enzymatic coupling (horseradish peroxidase/hydrogen peroxide) of selected pairs of compounds, one with a vic-trihydroxyphenyl moiety, and the other with an ortho-dihydroxyphenyl structure. Some of these compounds have been found to inhibit TPA-induced mice ear edema, nitric oxide (NO) synthesis, and arachidonic acid release by LPS-stimulated RAW 264.7 cells. Their cytotoxic activites against KYSE 150 and 510 human esophageal squamous cell carcinoma cells and HT 29 human colon cancer cells were also evaluated.

Impacts
The identification of the active antioxidants and health-promoting compounds, theaflavins in black tea will allow the researchers and industry to optimize the processing technology to maximize the content of these theaflavins in black tea products. It will have direct impact to the health of consumers. It will also improve the market value of black teas.

Publications

  • Huang, T.C., Fu, H.Y., Ho, C.-T. 2003. Comparative studies on some important quality attributes of firm tofu sterilized with traditional and autoclaving methods. J. Agric. Food Chem. 51:254−259.
  • Sang, S., Li, G., Tian, S., Lapsley, K., Stark, R.E., Rosen, R.T., Ho, C.-T. 2003. An unusual diterpene glycoside from the nuts of almond (Prunus amygdalus Batsch). Tetra. Lett. 44: 1199−1202.
  • She, Q.B., Ma, W.Y., Wang, M., Kaji, A., Ho, C.-T., Dong, Z. 2003. Inhibition of cell transformation by resveratrol and its derivatives: Differential effects and mechanisms involved. Oncogene 22: 2143-2150.
  • Sang, S., Liu, G., He, K., Zhu, N., Dong, Z., Zheng, Q., Rosen, R.T., Ho, C.-T. 2003. New unusual iridoids from the leaves of noni (Morinda citrifolia L.) show inhibitory effect on ultraviolet B-induced transcriptional activator protein-1 (AP-1) activity. Bioorg. Med. Chem. 11: 2499-2502.
  • Sang, S., Tian, S., Jhoo, J.W., Wang, H., Stark, R.E., Rosen, R.T., Yang, C.S., Ho, C.-T. 2003. Chemical studies of the antioxidant mechanism of theaflavins: Radical reaction products of theaflavin 3,3'-digallate with hydrogen peroxide. Tetra. Lett. 44: 5583-5587.
  • Sang, S., Tian, S., Wang, H., Stark, R.E., Rosen, R.T., Yang, C.S., Ho, C.-T. 2003. Chemical studies on antioxidant mechanism of tea catechins: Analysis of radical reaction products of epicatechin with peroxyl radicals. Bioorg. Med. Chem. 11: 3371-3378.
  • Jun, M., Fu, H.-Y., Hong, J., Wan, X., Yang, C.S., Ho, C.-T. 2003. Comparison of antioxidant activities of isoflavones from kudzu root (Pueraria lobata Ohwi). J. Food Sci. 68:, 2111-2116.
  • Shahidi, F., Ho, C.-T., Watanabe, S., Osawa, T., Editors. 2003. Food Factors in Health Promotion and Disease Prevention. ACS Symposium Series No. 851, American Chemical Society: Washington, D.C., 450 pages.
  • Ho, C.-T., Lin, J.K., Zheng, Q.Y. Editors. 2003. Oriental Foods and Herbs: Chemistry and Health Effects. ACS Symposium Series No. 859, American Chemical Society: Washington, D.C.


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

Outputs
We have continued our studies on the antioxidant mechanism of garcinol, a major bioactive compound from the fruits of Garcinia indica. Four major reaction products were isolated and identified from the oxidation reaction between garcinol and peroxyl radicals generated by thermolysis of the azo initiator azo-bis-isobutyrylnitrile (AIBN). Their structures were determined on the basis of detailed high field 1D and 2D spectral analysis. The identification of these products provides the first unambiguous proof that the double bond of the isopentenyl group is a principal site of the antioxidant reaction of garcinol. The induction of apoptosis in human leukemia HL-60 cells, the inhibition of NO generation, and the inhibition of LPS-induced iNOS gene expression by Western blot analysis by garcinol and its four oxidation products were investigated. We have studied the bioactivity of antioxidant compounds in the peel of citrus fruits. Tangeretin ( 5,6,7,8,4'-pentamethoxyflavone) is concentrated in the peel of citrus fruits. DNA flow cytometric analysis indicated that tangeretin blocked cell cycle progression at G1 phase in colorectal carcinoma COLO 205 cells. Over a 24 h exposure to tangeretin, the degree of phosphorylation of Rb was decreased after 12 h and G1 arrest developed. The protein expression of cyclins A, D1, and E reduced slightly under the same conditions. Immunocomplex kinase experiments showed that tangeretin inhibited the activities of cyclin-dependent kinases 2 (Cdk 2) and 4 (Cdk4) in a dose-dependent manner in the cell-free system. As the cells were exposed to tangeretin (50 mM) over 48 h a gradual loss of both Cdk2 and 4 kinase activities occurred. Tangeretin also increased the content of the Cdk inhibitor p21 protein and this effect correlated with the elevation in p53 levels. In addition, tangeretin also increased the level of the Cdk inhibitor p27 protein within 18 h. These results suggest that tangeretin either exerts its growth-inhibitory effects through modulation of the activities of several key G1 regulatory proteins such as Cdk2 and Cdk4 or mediates the increase of Cdk inhibitors p21 and p27. Theaflavins and thearubigins are major pigments of black tea. In the course of studies on the oxidation mechanism of tea polyphenols, a new type tea pigment, theadibenzotropolone A, together with theaflavin 3-gallate were formed by the reaction of (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG) with horseradish peroxidase in the presence of H2O2. The structure of theadibenzotropolone A was elucidated on the basis of MS and 2D NMR spectroscopic analyses. A compound containing two types of benzotropolone links is of great interest, since it shows that the galloyl ester group of theaflavin monogallate participates in further oxidative condensation reactions. This may provide an additional reaction pathway for the formation of thearubigins. The existence of this compound in black tea was characterized by LC/ESI-MS/MS.

Impacts
We have studied the antioxidant and other bioactivity of plant-derived compounds such as garcinol, orange peel bioflavonoids and tea polyphenols. We are working on the identification of natural antioxidants in other plants such as almond, quinoa, buck wheat and several spices. The findings will help promote the sales of these agricultural products and also improve the health of general public.

Publications

  • Ho, C.-T. and Zheng, Q. Y. (Ed). 2002. Quality Management of Nutraceuticals. ACS Symposium Series No. 803, American Chemical Society: Washington, D.C., 327 pages.
  • Morello, M.J., Shahidi, F. and Ho, C.-T. (Ed). 2002. Free Radicals in Food: Chemistry, Nutrition and Health Effects; ACS Symposium Series No. 807, American Chemical Society: Washington, D.C., 356 pages.
  • Sang, S., Lapsley, K., Rosen, R.T. and Ho, C.-T. 2002. New Prenylated Benzoic Acid and Other Constituents from Almond Hulls (Prunus amygdalus Batch). Journal of Agricultural and Food Chemistry 50, 607-609.
  • Rafi, M.M., Vastano, B.C., Zhu, N., Ho, C.-T., Ghai, G., Rosen, R.T., Gallo, M.A. and DiPaola, R.S. 2002. Novel Polyphenol Molecule Isolated from Licorice Root (Glycrrhiza glabra) Induces Apoptosis, G2/M Arrest and Bcl-2 Phosphorylation in Tumor Cell Lines. Journal of Agricultural and Food Chemistry 50, 677-684.
  • Zhu, N., Sheng, S., Sang, S., Jhoo, J.W., Bai, N., Karwe, M.V., Rosen, R.T. and Ho, C.-T. 2002. Triterpene Saponins from Debittered Quinoa (Chenopodium quinoa) Seeds. Journal of Agricultural and Food Chemistry, 865-867.
  • Sang, S., Cheng, X., Fu, H.Y., Shieh, D.E., Bai, N., Lapsley, K., Rosen, R.T., Stark, R.E. and Ho, C.-T. 2002. New Type Sesquiterpene Lactone from Almond Hulls (Prunus amygdalus Batch). Tetrahedron Letters 43, 2547-2549.
  • Sang, S., Lapsley, K., Jeong, W.S., Lachance, P.A., Rosen, R.T. and Ho, C.-T. 2002. Antioxidative Phenolic Compounds Isolated from Almond Skin (Prunus amygdalus Batsch). Journal of Agricultural and Food Chemistry 50, 2459-2463.
  • Fu, H.Y., Shieh, D.E. and Ho, C.-T. 2002. Antioxidant and Free Radical Scavenging Activities of Edible Mushrooms. Journal of Food Lipids 9, 35-46.
  • Sang, S., Cheng, X., Stark, R.E., Rosen, R.T.; Yang, C.S. and Ho, C.-T. 2002. Chemical Studies on Antioxidant Mechanism of Tea Catechins: Analysis of Radical Reaction Products of Catechin and Epicatechin with 2,2-Diphenyl-1-picrylhydrazyl. Bioorganic and Medicinal Chemistry 10, 2233-2237.
  • Lo, A.H., Liang, Y.C.,; Lin-Shiau, S.Y., Ho, C.-T. and Lin, J.K. 2002. Carnosol, An Antioxdant in Rosemary, Suppresses Inducible Nitric Oxide Synthase Through Down-Regulating Nuclear Factor kappaB in Mouse Macrophages. Carcinogenesis 23, 983-991.
  • Kamdem, R.E., Sang, S. and Ho, C.-T. 2002. Mechanism of the Superoxide Scavenging Activity of Neoandrographolide - A Natural Product from Andrographis paniculata Nees. Journal of Agricultural and Food Chemistry 50, 4662-4665.
  • Sang, S., Kikuzaki, H., Lapsley, K., Nakatani, N., Rosen, R.T. and Ho, C.-T. 2002. Spingolipid and Other Constituents from Almond Nuts (Prunus amygdalus Batsch). Journal of Agricultural and Food Chemistry 50, 4709-4712
  • Meng, X., Sang, S., Lu, H., Lee, M.J., Zhu, N., Sheng, S., Ho, C.-T. and Yang, C.S. 2002. Identifiation and Characterization of Methylated and Ring-Fission Metabolites of Tea Catechins Formed in Human, Mice, and Rats. Chemical Research in Toxicology 15, 1042-1050.
  • Liang, Y.C., Tsai, D.C., Lin-Shiau, S.Y., Chen, C.F., Ho, C.-T. and Lin, J.K. 2002. Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Inflammatory Skin Edema and Ornithine Decarboxylase Activity by Theaflavin-3,3'-digallate in Mouse. Nutrition and Cancer 42, 217-223.
  • Sang, S., Wang, M., He, K., Liu, G., Dong, Z., Vladimir B., Zheng, Q.Y., Ghai, G., Rosen, R.T. and Ho, C.-T. 2002. Chemical Components in Noni Fruits and Leaves (Morinda citrifolia L.) In Quality Management of Nutraceuticals; Edited by C.-T. Ho and Q.Y. Zheng; ACS Symposium Series No. 803, American Chemical Society: Washington, D.C., pp. 134-150.
  • Wang, M., Zhu, N., Jin, Y., Belkowitz, N. and Ho, C.-T. 2002. A Quantitative HPLC Method for the Quality Assurance of Goldenseal Products in the US Market. In Quality Management of Nutraceuticals; Edited by C.-T. Ho and Q.Y. Zheng; ACS Symposium Series No. 803, American Chemical Society: Washington, D.C., pp. 199-213.
  • Vastano, B.C., Rafi, M.M., DiPaola, R.S., Zhu, N., Ho, C.-T., Rella, A.T., Ghai, G. and Rosen, R.T. 2002. Bioactive Homoisoflavonoids from Vietnamese Coriander or Pak Pai (Polygonum odoratum). In Quality Management of Nutraceuticals; Edited by C.-T. Ho and Q.Y. Zheng; ACS Symposium Series No. 803, American Chemical Society: Washington, D.C., pp. 269-280.
  • Zhu, N., Rafi, M.M., Li, D., LaVoie, E.J.; DiPaola, R.S., Badmaev, V., Ghai, G., Rosen, R.T. and Ho, C.-T. 2002. Analysis of Bioactive Ferulates from Gum Guggul (Commiphora wightii). In Quality Management of Nutraceuticals; Edited by C.-T. Ho and Q.Y. Zheng; ACS Symposium Series No. 803, American Chemical Society: Washington, D.C., 2002, pp. 281-291.
  • Sang, S., Zhu, N., Lin-Shiau, S.Y., Lin, J.K. and Ho, C.-T. 2002. Antioxidant Activity of Flavonols and Flavonol Glycosides in Oolong Tea. In Quality Management of Nutraceuticals; Edited by C.-T. Ho and Q.Y. Zheng; ACS Symposium Series No. 803, American Chemical Society: Washington, D.C., pp. 292-303.
  • Masuda, H., Ueno, T., Muranishi, S., Irisawa, S. and Ho, C.-T. 2002. Inhibition of Citral Deterioration. In Free Radicals in Food: Chemistry, Nutrition and Health Effects; Edited by M.J. Morello, F. Shahidi and C.-T. Ho; ACS Symposium Series No. 807, American Chemical Society: Washington, D.C., pp. 176-187.
  • Zhu, N., Huang, T.C., Lin, J.K., Yang, C.S. and Ho, C.-T. 2002. Free Radical and Oxidative Reactions of (-)-Epigallocatechin and (-)-Epigallocatechin Gallate, Two Major Polyphenols in Green Tea. In Free Radicals in Food: Chemistry, Nutrition and Health Effects; Edited by M.J. Morello, F. Shahidi and C.-T. Ho; ACS Symposium Series No. 807, American Chemical Society: Washington, D.C., pp. 213-223.
  • Lin, J.K., Chen, P.C., Ho, C.-T. and Lin-Shiau, S.Y. 2002. Inhibition of Xanthine Oxidase and NADPH Oxidase by Tea Polyphenols. In Free Radicals in Food: Chemistry, Nutrition and Health Effects; Edited by M.J. Morello, C.-T. Ho and F. Shahidi; ACS Symposium Series No. 807, American Chemical Society: Washington, D.C., pp. 264-281.
  • Lee, T.C. and Ho, C.-T. (Ed). 2002. Bioactive Compounds in Foods: Effects of Processing and Storage; ACS Symposium Series No. 816, American Chemical Society: Washington, D.C., 260 pages.
  • Huang, T.C., Chen, M.H. and Ho, C.-T. 2002. Stability of Biologically Active Pyridoxal and Pyridoxal Phosphate in the Presence of Lysine. In Bioactive Compounds in Foods: Effects of Processing and Storage; Edited by T.C. Lee and C.-T. Ho; ACS Symposium Series No. 816, American Chemical Society: Washington, D.C., pp. 143-154.
  • Sang, S., Tian, S., Meng, X., Stark, R.E., Rosen, R.T., Yang, C.S. and Ho, C.-T. 2002. Theadibenzotropolone A, A New Type of Pigment from Enzymatic Oxiation of (-)-Epicatechin and (-)-Epigallocatechin Gallate and Characterized from Black Tea by LC/MS/MS. Tetrahedron Letters 43, 7129-7133.
  • Pan, M.H., Chen, W.J., Lin-Shiau, S.Y., Ho, C.-T. and Lin, J.K. 2002. Tangeretin Induces Cell-cycle G1 Arrest through Inhibiting Cyclin-dependent Kinases 2 and 4 Activities as well as Elevating Cdk Inhibitors p21 and p27 in Human Colorectal Carcinoma Cells. Carcinogenesis 23, 1677-1684.
  • Sang, S., Lao, A., Chin, C.K., Wang, Y., Rosen, R.T. and Ho, C.-T. 2002. Antifungal Constituents from the Seeds of Allium fistulosum L. Journal of Agricultural and Food Chemistry 50, 6318-6321.
  • Sang, S., Liao, C.H., Pan, M.H., Rosen, R.T., Lin-Shiau, S.Y., Lin, J.K., Ho, C.-T. Chemical Studies on Antioxidant Mechanism of Garcinol: Analysis of Radical Reaction Products of Garcinol with Peroxyl Radicals and Their Antitumor Activities. Tetrahedron 2002, 58, 10095-10102.


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

Outputs
Morinda citrifolia (Rubiaceae), commonly known as noni, native to certain regions bordering the Indian Ocean such as Tahidi and Samoa as well as Hawaii. The bark, stem, roots, leaves, and fruits have been used traditionally as a folk remedy for many diseases including diabetes, hypertension, and cancer. We have done a complete analysis of the components in noni fruits, leaves and roots. Several new and known iridoids and several known flavonol glycosides was isolated from the leaves of Morinda citrifolia. Their antioxidative activities were measured. All of these compounds showed DPPH free radical scavenging activity at the concentration of 30 microM. Garcinol, a polyisoprenylated benzophenone, purified from Garcinia indica fruit rind, displays antioxidant properties and is thought to act as an antioxidant in biological systems. However, the mechanisms of its antioxidant reactions remain unknown. We have characterized the reaction products of garcinol with a stable radical, 2,2-diphenyl-1-picrylhydrazyl (DPPH). Structural elucidation of these products can provide insights into specific mechanisms of antioxidant reactions. Two major reaction products, GDPPH-1 and GDPPH-2, were isolated and identified for the first time. Their structures were determined on the basis of detailed high-field 1D and 2D spectral analysis. The identification of these products provides the first unambiguous proof that the principal sites of antioxidant reactions are on the phenolic ring and the 1,3-diketone part of garcinol. The induction of apoptosis in human leukemia HL-60 cells, the inhibition of NO generation, the effects on the activity of MMP, and the inhibitory effects on H2O2 production of TPA-stimulate HL-60 cells by garcinol and its two oxidant products were investigated.

Impacts
We have isolated and identified several antioxidant compounds from noni, a known healthy fruit of Hawaii. We have shown that several of these compounds also have other bioactivity such as inhibition of activitor protein-1 which may explain the anticancer property of noni. Our finding may help the growth and marketing of noni in US. We are working on the identification of natural antioxidants in other plants such as almond, quinoa, buck wheat and several spices. The findings will help promote the sales of these agricultural products and also improve the health of general public.

Publications

  • Sang, S.; He, K.; Liu, G.; Zhu, N.; Wang, MI; Jhoo, J.W.; Zheng, Q.; Dong, Z.; Ghai, G.; Rosen, R. T.; Ho, C.-T. Citrifolinin A, a New Unusual Iridoid with Inhibition of Activator Protein-1 (AP-1) from the Leaves of Noni (Morinda citrifolia L.). Tetrahedron Letters 2001, 42, 1823-1825.
  • Pan, M.H.; Chang, W.L.; Lin-Shiau, S.Y.; Ho, C.-T.; Lin, J.K. Induction of Apoptosis by Garcinol and Curcumin through Cytochrome c Release and Activation of Caspases in Human Leukemia HL-60 Cells. Journal of Agricultural and Food Chemistry 2001, 49, 1464-1474.
  • Zhu, N.; Rafi, M.; Xin, J.; DiPaola, R.S.; Chin, C.K.; Badmaev, V.; Ghai, G.; Rosen, R.T.; Ho, C.-T. Bioactive Constituents from Gum Guggul (Commiphora wightii). Phytochemistry 2001, 56, 723-727.
  • Zhu, N.; Wang, MI; Wei, G.J.; Lin, J.K.; Yang, C.S.; Ho, C.-T. Identification of Reaction Products of (-)-Epigallocatechin, (-)-Epigallocatechin Gallate and Pyrogallol with 2,2-Diphenyl-1-picrylhydrazyl Radical. Food Chemistry 2001, 73, 345-349.
  • Sang, S.; He, K.; Liu, G.; Zhu, N.; Cheng, X.; Wang, M.; Zheng; Q.; Dong, Z.; Ghai, G.; Rosen, R.T.; Ho, C.-T. A New Unusual Iridoid with Inhibition of Activator Protein-1 (AP-1) from the Leaves of Morinda citrifolia L. Organic Letters 2001, 3, 1307-1309.
  • Meng, X.; Lee, M.J.; Li, C.; Sheng, S.; Zhu, N.; Sang, S.; Ho, C.-T.; Yang, C.S. Formation and Identification of 4'-O-Methyl-(-)-epigallocatechin in Humans. Drug Metabolism and Disposition 2001, 29, 789-793.
  • Zhu, N.; Kikuzaki, H.; Vastano, B.C.; Nakatani, N.; Karwe, M.V.; Rosen, R.T.; Ho, C.-T. Ecdysteroids of Quinoa Seeds (Chenopodium quinoa Willd). Journal of Agricultural and Food Chemistry 2001, 49, 2576-2578.
  • Sang, S.; Cheng, X.; Zhu, N.; Wang, M.; Jhoo, J.W.; Stark, R.E.; Badmaev, V.; Ghai, G.; Rosen, R.T.; Ho, C.-T. Iridoid Glycosides from the Leaves of Morinda citrifolia. Journal of Natural Products 2001, 64, 799-800.
  • Zhu, N.; Sheng, S.; Li, D.; LaVoie, E.J.; Karwe, M.V.; Rosen, R.T.; Ho, C.-T. Antioxidative Flavonoid Glycosides from Quinoa Seeds (Chenopodium quinoa Willd). Journal of Food Lipids 2001, 8, 37-44.
  • Liu, G.; Bode, A.; Ma, W.Y.; Sang, S.; Ho, C.-T.; Dong, Z.. Two Novel Glycosides from the Fruits of Morinda citrifolia (Noni) Inhibit AP-1 Transactivation and Cell Transformation in the Mouse Epidermal JB6 Cell Line. Cancer Research 2001 61, 5749-5756.
  • Sang, S.; Cheng, X.; Zhu, N.; Stark, R.E.; Badmaev, V.; Ghai, G.; Rosen, R.T.; Ho, C.-T. Flavonol Glycosides and Novel Iridoid Glycoside from the Leaves of Morinda citrifolia. Journal of Agricultural and Food Chemistry 2001, 49, 4479-4481.
  • Sun, Ting; Ho, C.-T. Antiradical Efficiency of Tea Components. Journal of Food Lipids 2001, 8, 231-238.
  • Sang, S.; Zou, M.; Xia, Z.; Lao, A.; Chen, Z.; Ho, C.-T. New Spirostanol Saponins from Chinese Chives (Allium tuberosum). Journal of Agricultural and Food Chemistry 2001, 49, 4780-4783.
  • Sang, S.; Pan, M.H.; Cheng, X.; Bai, N.; Stark, R.E.; Rosen, R.T.; Lin-Shiau, S.Y.; Lin, J.K.; Ho, C.-T. Chemical Studies on Antioxidant Mechanism of Garcinol: Analysis of Radical Reaction Products from Garcinol and Their Antitumor Activities. Tetrahedron 2001. 57, 9931-9938.
  • Zhu, N.; Kikuzaki, H.; Sheng, S.; Rafi, M.M.; Wang, M.; Nakatani, N.; DiPaola, R.S.; Rosen, R.T.; Ho, C.-T. Furanosesquiterpenoids of Commiphora myrrha. Journal of Natural Products 2001, 64, 1460-1462.
  • Jhoo, J.W.; Sang, S.; He, K.; Cheng, X.; Zhu, N.; Stark, R.E.; Zheng, Q.Y.; Rosen, R.T.; Ho, C.-T. Characterization of the Triterpene Saponins of the Roots and Rhizomes of Blue Cohosh (Caulophyllum thalictroides). Journal of Agricultural and Food Chemistry 2001, 49, 5969-5974.


Progress 10/01/99 to 12/31/99

Outputs
Rosemary and sage are common spices used in food. In our recent search of cancer chemopreventive agents from spices, the alcohol extracts of rosemary and sage showed strong antumorigenic activities. Rosemary and sage extracts contain active antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids. In the last three months, we used chromatographic methods to separate and purify compounds from these spices and MS and NMR spectrometry to identify the isolated compounds. Several new phenolic acid glycoside compounds were identified in sage. Their antioxidant activities have been measured. They could contribute to the total antioxidant and anti-tumorigenic activity of sage extract.

Impacts
Rosemary and sage are common spices used in processed foods. Identification of antioxidative and antitumorgenic components in them will promote their uses in functional foods.

Publications

  • Chen, Y., Wang, M., Rosen, R.T., Ho, C.-T. 1999. 2,2-Diphenyl-1-picrylhydrazyl Radical-Scavenging Active Components from Polygonum multiforum Thunb. J. Agric. Food Chem. 47:2226-2228.
  • Chen, Y., Zhu, N., Lo, C.Y., Wang, M., Ho, C.-T. 1999. Process-induced Health Promoting Substances in Food. Food Rev. Internat. 15:473-501.
  • Chen, Y.C., Liang, Y.C., Lin-Shiau, S.Y., Ho, C.-T., Lin, J.K. 1999. Inhibition of TPA-Induced Protein Kinase C and Transcription Activator Protein-1 Binding Activities by Theaflavin-3,3'-digallate from Black Tea in NIH3T3 Cells. J. Agric. Food Chem. 47:1416-1421.
  • Jin, Y., Wang, M., Rosen, R.T., Ho, C.-T. 1999. Thermal Degradation of Sulforaphane in Aqueous Solution. J. Agric. Food Chem. 47:3121-3123.
  • Liang, Y.C., Chen, Y.C., Lin, Y.L., Lin-Shiau, S., Ho, C.-T., Lin, J.K. 1999. Suppression of Extracellular Signals and Cell Proliferation by the Black Tea Polyphenol, Theaflavin-3,3'-digallate. Carcinogenesis 20:733-736.
  • Lin, Y.L., Tsai, S.H., Lin-Shiau, S.Y., Ho, C.-T., Lin, J.K. 1999. Theaflavin-3,3'-digallate from Black Tea Blocks the Nitric Oxide Synthase by Down-regulating the Activation of NF-kB in Macrophages. Eur. J. Pharmacology 367:379-388.
  • Wang, M., Jin, Y., Ho, C.-T. 1999. Evaluation of Resveratrol Derivatives as Potential Antioxidants and Identification of a Reaction Product of Resveratrol and 2,2-Diphenyl-1-picrylhydrazyl Radical. J. Agric. Food Chem. 47:3974-3977.