Progress 01/01/05 to 12/31/10
Outputs
OUTPUTS: Conducting trainings for approximately 50 postdoctors in the field of botanical medicine research has been an annual event during the project period. I have trained them, by lectures and special seminar presentations, on how to collect botanical samples, prepare botanical extracts, test and interpret in vitro and vivo experimental results, and develop isolation and purification methods to identify active compounds. Personal mentoring for faculty members and students who need knowledge on preparing botanical samples was also provided on numerous occasions. I have served as an on-site consultant for many of my colleagues and students when it comes to botanical medicine research. I also played the role of facilitating inter-institutional and inter-disciplinary collaborations between agricultural departments in food science and nutrition and medical research institutions such as Pennington Biomedical Research Center, the LSU Veterinary School, LSU Health Sciences Center in both New Orleans and Shreveport, and the M.D. Anderson Cancer Center. Products include a unique curricula designed to bridge chemistry-oriented and biology-oriented researchers so each discipline gains better understanding of the other. The "Botanical Drug Research" course has been a unique comprehensive overview that benefits both disciplines. During this project period, eight patent applications were filed. One of the most significant patent applications is the discovery of synergistic natural ingredients consisting of three natural food compounds that, in animal studies, significantly prevented the elevation of blood cholesterol and triglycerides, and the onset of obesity. This result has been published in peer-reviewed journals and created interest and opportunities for commercial product development. Another significant patent technology disclosed a critical discovery of the solubilizing properties of natural compounds that may transform the research and development paradigm for nutritional, agrochemical, and pharmaceutical areas of research. This one-of-the-kind discovery has shifted my research focus to natural nano-platform technology. These discoveries in botanical medicine research and the associated extract techniques using chromatographic fingerprinting and identification of active compounds has resulted in several collaborative relationships and publications. PARTICIPANTS: Dr. Dong Liu, a natural product chemist, worked on the fractionation and isolation. Gar Yee Koh, M.S. student worked on the extraction and purification of the Chinese sweet leaf tea extract using alcohol precipitation. Dr. May Liu and Dr. Fang Zhang worked on the fingerprinting analyses. Scientists from the LSU Pennington Biomedical Research Center: Jianping Ye, M.D.; Aamir Zuberi, Ph.D.; Kenneth J. Eilertsen, Ph.D.; Frank L. Greenway, M.D., LSU Health Sciences Center in New Orleans; Eugene A. Woltering, M.D., LSU Agricultural Center: Roy J. Martin, Ph.D., M.D. Anderson Cancer Center; Peiying Yang, Ph.D.; Dr. Guixin Chou, visiting professor from the Shanghai University of Traditional Chinese Medicine, worked on the analyses of the sweetgum fruit and the sweet leaf tea. Heather Kirk, Ph.D. student worked on the screening of Louisiana plants for epigenome modulation activities. TARGET AUDIENCES: Target audiences include research scientists in the fields of botanical extraction and purification, medicinal chemistry, and bioactivity screening and testing. Product development groups interested in botanical products, nutritional ingredients, methods of purification, isolation of active compounds are target audiences. We have been making major efforts to deliver science-based knowledge to people through publications, presentations, and newsletter articles. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Completion of three NIH-funded botanical research projects and several client sponsored projects caused a significant change in our knowledge on effectively and productively researching botanical extracts. Some new knowledge on effective purification, by alcoholic precipitation, of biologically active compounds has resulted in new techniques that can potentially be applied on broad-scale projects. A new technique to aid in the selection of chemical markers. This should aid in standardizing complex botanical extract evaluation. A major application of this technique was the creation of a novel methodology of separating difficult-to-separate compounds under the conventional separation techniques. Specifically, capsaicin and its close analogues can be effectively separated and purified. This technique has the potential to improve all of our chemical separation needs. The patented technology and newly developed techniques can potentially result in new and safer products for people to improve and manage their health (e.g. obesity, protein metabolism, etc.).
Publications
- Wenxing Chen, Yan Luo, Lei Liu, Hongyu Zhou, Baoshan Xu, Xiuzhen Han, Tao Shen, Zhijun Liu, Yin Lu, and Shile Huang. 2010. Cryptotanshinone Inhibits Cancer Cell Proliferation by Suppressing Mammalian Target of Rapamycin-Mediated Cyclin D1 Expression and Rb Phosphorylation. Cancer Prev Res; 3(8); 1015-25.
- Guixin Chou, Shun-Jun Xu, Dong Liu, Gar Yee Koh, Jian Zhang, and Zhijun Liu. 2009. Quantitative and fingerprint analyses of Chinese sweet tea plant (Rubus Suavissimus S. Lee). J. Agric. Food Chem. 57: 1076-1083. (PMCID: PMC2680688; NIHMSID: NIHMS87845)
- Wedge, David; Klun, Jerome; Tabanca, Nurhayat; Demirci, Betul; Ozek, Temel; Baser, K. Husnu; Liu, Zhijun; Zhang, Sui; Cantrell, Charles;Zhang, Jian. 2009. Bioactivity-guided Fractionation and GC-MS Fingerprinting of Angelica sinensis and A. archangelica Root Components for Antifungal and Mosquito Deterrent Activity. Journal of Agricultural and Food Chemistry. 57(2):464-70.
- Zhijun Liu. 2008. Preparation of botanical samples for biomedical research. Endocrine, Metabolic & Immune Disorders - Drug Targets. 8: 112-121.
- Yin, Jun, Aamir Zuberi, Zhanguo Gao, Dong Liu, Zhijun Liu, William T. Cefalu, Jianping Ye. 2008. Effect of Shilianhua extract and its fractions on body weight of obese mice. Metabolism Clinical and Experimental 57 (Suppl 1): S47-S51.
- Greenway, Frank L., Zhijun Liu, Ying Yu, Mary K. Caruso, Andrew Roberts, Joshua Schwimer, Alok K. Gupta, Drake Bellanger, Thomas Guillot, Eugene A. Woltering. 2007. An Assay to Measure Angiogenesis in Human Fat Tissue. Obesity Surgery 17: 510-515.
- Oner, F. Hakan, Yanno Bezerra, Gholam A. Peyman, Mandi D. Conway, James M. Lewis, Zhijun Liu, Frank Greenway, Eugene A. Woltering. 2007. Antiangiogenetic Effect of a Chinese Sweet Leaf Tea Extract in Experimental Corneal Neovascularization. Pharmaceutical Biology 45(1): 44-47.
- Andrew T. Roberts, Corby K. Martin, Zhijun Liu, Ronald J. Amen, Eugene A. Woltering, Jennifer C. Rood, Mary K. Caruso, Ying Yu, Hui Xie, Frank L. Greenway. 2007. The safety and efficacy of a dietary herbal supplement and gallic acid for weight loss. Journal of Medicinal Food 10(1): 184-188.
- William T Cefalu, Jianping Ye, Aamir Zuberi, David Ribnicky, Ilya Raskin, Zhijun Liu, Zhong Q Wang, Phillip J Brantley, Luke Howard and Michael Lefevre. 2008. Botanicals and metabolic syndrome. Am J Clin Nutr 87(suppl): 481S-7S.
- Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping. 2008. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 294: E148-E156.
- Liu, Dong, Joshua Schwimer, Zhijun Liu, Eugene Woltering, and Frank L. Greenway. 2008. Antiangiogenic effect of curcumin in pure versus in extract forms. Pharmaceutical Biology 46: 677-682.
- David A. York, Sonyja Thomas, Frank L. Greenway, Zhijun Liu, Jennifer C. Rood. 2007. The Effect of NT, an Herbal Supplement, on Body Weight in Rats. Chinese Medicine 2:10.
- Zhang, Jian,Ying Yu, Dong Liu, and Zhijun Liu. 2007. Extraction and composition of three naturally occurring anti-cancer alkaloids in Camptotheca acuminata seed and leaf extracts. Phytomedicine 14: 50-56.
- Zhu, Bin, Qingbiao Wang, Esben F. Roge, Peng Nan, Zhijun Liu, Yang Zhong. 2006. Chemical variation in leaf oils of Pistacia chinensis from five locations in China. Chemistry of Natural Products. 42(4): 422-425.
- Liu, Zhijun, Joshua Schwimer, Dong Liu, James Lewis, Frank L. Greenway, David A. York, Eugene A. Woltering. 2006. Gallic acid is partially responsible for the anti-angiogenic activities of Rubus leaf extract. Phytotherapy Research 20(9): 806-813.
- Frank L. Greenway, Zhijun Liu, Corby K. Martin, Wei Kai-yuan, James Nofziger, Jennifer C. Rood, Ying Yu, and Ronald J. Amen. 2006. Safety and Efficacy of NT, an Herbal Supplement, in Treating Human Obesity. International Journal of Obesity April 25: 1-5.
- Zhao, Jiayuan, Jimei Liu, Xiaoyan Zhang, Zhijun Liu, Tashi Tsering, Yang Zhong and Peng Nan. 2006. Chemical Composition of the Essential Oils of Three Wild Bergenia Species from Western China. Flavour and Fragrance Journal 21: 431-434.
- Liu, Jimei, Peng Nan, Qiong Tsering, Tashi Tsering, Zhankui Bai, Li Wang, Zhijun Liu, and Yang Zhong. 2006. Volatile constituents of the leaves and flowers of Salvia przewalskii Maxim. from Tibet. Flavour and Fragrance Journal 21: 435-438.
- Qiong WU, Da-Xu FU, Ai-Jun HOU, Guang-Qing LEI, Zhijun Liu, Jia-Kuan CHEN, and Tong-Shui ZHOU. 2005. Antioxidative Phenols and Phenolic Glycosides from Curculigo orchioides. Chem. Pharm. Bull. 53(8): 1065-1067.
- Wang, Qingbiao, Yong Yang, Xiaomin Zhao, Bin Zhu, Peng Nan, Jiayuan Zhao, Li Wang, Fan Chen, Zhijun Liu, and Yang Zhong. 2006. Chemical variation in the essential oil of Ephedra sinica from Northeastern China. Food Chemistry 98: 52-58.
- Liu, Dong, Zhanguo Gao, Jian Zhang, Jianping Ye, and Zhijun Liu. 2005. Bioassay-guided fractionation of the Rubus suavissimus leaf extracts possessing NF-Kappa-B inhibitory activities and a separable cytotoxicity. Pharmaceutical Biology 43(8): 713-717.
- Liu, Zhijun, Joshua Schwimer, Dong Liu, Frank L. Greenway, Catherine T. Anthony, and Eugene A. Woltering. 2005. Black Raspberry Extract and Fractions Contain Angiogenesis Inhibitors. Journal of Agriculture and Food Chemistry 53(10):3909-3915.
- Z Li, Z Liu. 2005. Plant regeneration from leaf petiole in Camptotheca acuminata. In Vitro Cellular and Developmental Biology - Plant 41(3):262-265.
- Lang, Cynthia, Zhijun Liu, H.Wayne Taylor, and David G. Baker. 2005. Effect of Eucommia ulmoides on Systolic Blood Pressure in the Spontaneous Hypertensive Rat. American Journal of Chinese Medicine 33(2): 215-230.
- Li, Zhanhai and Zhijun Liu. 2005. Camptothecin production in Camptotheca acuminata hydroponic culture and nitrogen enrichments. Canadian Journal of Plant Science 85: 447-452.
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: Three peer-reviewed publications were produced during this past year. One publication reported an effective purification method for active compounds of a leaf tea extract. Another reported the anti-diabetes bioactivity of a fractionated plant extract. And the third described the antifungal activity of a plant essential oil. A patent was filed during this period. This patent claimed a three-compound composition isolated from a leaf tea and a method of using this composition to treat obesity and prevent cancer recurrence. PARTICIPANTS: Dr. Dong Liu, a natural product chemist, worked on the fractionation and isolation. Gar Yee Koh, M.S. student worked on the extraction and purification of the Chinese sweet leaf tea extract using alcohol precipitation. Dr. May Liu and Dr. Fang Zhang worked on the fingerprinting analyses. These organizations and collaborators worked with the PI. LSU Pennington Biomedical Research Center: Jianping Ye, M.D., Tel. 225-763-3163, yej@pbrc.edu; Aamir Zuberi, Ph.D., Tel. 225-763-2576, Aamir.Zuberi@pbrc.edu; Kenneth J. Eilertsen, Ph.D., Tel.: 225-763-0275, Kenneth.Eilertsen@pbrc.edu; LSU Health Sciences Center in New Orleans: Eugene A. Woltering, M.D., Tel. 504-464-8500, EWolte@lsuhsc.edu; LSU Agricultural Center: Roy J. Martin, Ph.D., Tel. 225-578-2284, RMartin@agcenter.lsu.edu; M.D. Anderson Cancer Center: Peiying Yang, Ph.D., Tel. 713-563-7531,pyang@mdanderson.org TARGET AUDIENCES: The new formulation has shown remarkable anti-obesity effects, which will allow the development of medicinal foods or botanical drugs. It has the potential to help humans in many ways. The formulation has the advantages of proper dosing regimen for human uses, a non-toxic safety profile, and potential synergistic effects. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Experimental results showed that the three compound-based leaf tea extract was effective in preventing unhealthy body weight gain of obese-prone rats by 22% and abdominal fat gain by 48%. In addition this extract reduced cholesterol by 20%, triglycerides by 50%, and lowered overall blood glucose levels. These findings provide a solid foundation for the justification of human clinical investigations. As a result, we have designed a human clinical trial to determine if the three-compounds-based leaf tea extract would cause significant weight loss in human populations. The trial is scheduled to begin in 2010 at the Pennington Biomedical Research Center in collaboration with Dr. Frank Greenway. If the human trial results support the use of the patented composition for treating obesity, it has the potential to (1) create new business opportunities to manufacture and market natural anti-obesity products, and (2) provide an effective natural agent for combating obesity.
Publications
- David E. Wedge, Nurhayat Tabanca, Blaire J. Sampson, Christopher Werle, Betul Demerci, K. Husnu Can Baser, Peng Nan, Jia Duan, Zhijun Liu. 2009. Antifungal and insecticidal activity of two Juniperus essential oils. Natural Product Communications. 4(1): 123-127.
- Koh G.Y., Chou G., Liu Z. 2009. Purification of a water extract of chinese sweet tea plant (Rubus suavissimus S. Lee) by alcohol precipitation. J. Agric. Food Chem. 57: 5000-5006.
- Yin J, Zuberi A, Gao Z, Liu D, Liu Z, Ye J. 2009. Shilianhua extract inhibits GSK-3β and promotes glucose metabolism. Am. J. Physiol. Endocrinol. Metab. 296: 1275-1280.
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: Productive experiments have been conducted in the preparation of botanical extracts, fractionation, isolation, and structural elucidation of bioactive compounds. The shilianhua (SLH) project was concluded and the data was published indicating SLH was not an effective anti-diabetes agent. SLH's anti-inflammatory effect, however, was apparent and was further investigated. A bioassay-directed fractionation approach was taken, which resulted in a potent fraction (F100) for decreasing inflammation. A chromatogprahic fingerprint of the active extract was generated and reported in a submitted manuscript. In a related research, ginger root extracts from several sources were prepared and analyzed for gingerol contents. Chromatographic fingerprinting methods were established and analyses for gingerols were conducted. A manuscript on this work has been submitted. The prepared ginger root extracts and gingerols were investigated in human tissue based angiogenesis assays and positive results have been found. Animal studies indicated that ginger extracts were not effective in weight loss. These research accomplishments were results of collaboration with Pennington Biomedical Research Center of the LSU System and were funded by NIH and LSU Agricultural Center Tech Transfer fund. Another major research accomplishment was the award of the sweetgum project in 2008 by the National Center for Complementary and Alternative Medicine of the NIH collaboratively with the M.D. Anderson Cancer Center. This extract was found to possess potent cytotoxicity against a panel of human cancer cell lines and reduced tumor growth in animal models. The Chinese sweet leaf tea research project entered its second year in 2008 funded by NIH. A series of fractionation steps were initiated and a chromatographic fingerprinting method was established in LC/MS and the quality analysis was accepted for publication in the Journal of Agriculture and Food Chemistry. This was a collaborative project with the LSU Health Sciences Center and the M.D. Anderson Cancer Center to investigate the leaf extract's antiangiogenic properties for potential cancer prevention from recurrence. In 2008, the mechanisms of action were revealed for the anti-angiogenic sweet leaf tea extract. We continued our research on testing Louisiana native plants collected and prepared last year. In collaboration with the LSU Health Sciences Center, LSU AgCenter, and LSU Pennington Biomedical Research Center scientists, 10 of the 50 plant extracts were evaluated for anti-angiogenic activities, anti-obesity (via reduced food intake) properties, and for epigenome modulating activities. We also tested Louisiana native plants for anti-bacterial activities related to oral health in collaboration with researchers at the School of Dentistry of the LSU Health Sciences Center in New Orleans. PARTICIPANTS: Dr. Dong Liu, a natural product chemist, worked on the shilianhua and ginger projects. Dr. Guixin Chou, visiting professor from the Shanghai University of Traditional Chinese Medicine, worked on the analyses of the sweetgum fruit and the sweet leaf tea. Heather Kirk, Ph.D. student worked on the screening of Louisiana plants for epigenome modulation activities. Gar Yee Koh, M.S. student worked on the extraction and purification of the Chinese sweet leaf tea extract. Dr. Shunjun Xu, a postdoc in natural product analyses, worked on the analyses of Chinese sweet leaf tea with LC/MS instrumentation. Dr. May Liu worked on the ginger preparation methods and analyses. These organizations and collaborators worked with the PI. LSU Pennington Biomedical Research Center: Frank L. Greenway, M.D., Tel. 225-763-2578, GreenwFL@pbrc.edu; Jianping Ye, M.D., Tel. 225-763-3163, yej@pbrc.edu; Aamir Zuberi, Ph.D., Tel. 225-763-2576, Aamir.Zuberi@pbrc.edu; Kenneth J. Eilertsen, Ph.D., Tel.: 225-763-0275, Kenneth.Eilertsen@pbrc.edu; LSU Health Sciences Center in New Orleans: Eugene A. Woltering, M.D., Tel. 504-464-8500, EWolte@lsuhsc.edu; LSU Agricultural Center: Roy J. Martin, Ph.D., Tel. 225-578-2284, RMartin@agcenter.lsu.edu; M.D. Anderson Cancer Center: Robert A. Newman, Ph.D., Tel. 713-563-7543,rnewman@mdanderson.org; Peiying Yang, Ph.D., Tel. 713-563-7531,pyang@mdanderson.org TARGET AUDIENCES: Knowledge and information generated from this research project have multiple audiences. The public has been better informed through these scientific investigations into the efficacy of health claims for common foods or spice products they consume such as shilianhua and ginger. The proprietary technologies provide new opportunities for pharmaceutical and nutraceutical companies. The techniques and knowledge developed throguh fractionation and identification of bioactive compounds in botanical samples continues to support small and/or existing companies rethink tradditional production methods. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
The shilianhua's negative results have been published informing the general public that it may not be effective in causing weight loss based on scientific investigations. The proprietary knowledge of the sweetgum fruit extract's anti-cancer property, when further investigated, adds another potential, novel therapy method to battle late-stage prostate cancer and forms new start-up companies. New knowledge from the ginger root research will lead to further and better designed investigations over their potential as anti-angiogenic agent, which may have wide applications for cancer prevention, diabetic retinopathy, and psoriasis. Because of the multidisciplinary nature of my research crossing the natural product chemistry and medical and biological boundaries, skills in communications with overlapping common languages have been continuously developed and strengthened. As a result of this learning, multidisciplinary collaborations have become more efficient and productive. My laboratory focus on fractionation and analyses of study agents has now become an integral part of a research team supporting six research labs in the LSU System as well as outside research units. My lab also contributes to product development for several small companies that lack research capabilities. Proprietary technologies have been embraced by inquiries and meetings for potential license discussions.
Publications
- Zhijun Liu. 2008. Preparation of botanical samples for biomedical research. In the "Hot Topics" issue on Botanical Treatments for Diabetes and Obesity. The Journal Endocrine, Metabolic & Immune Disorders - Drug Targets (EMID-DT).
- Xu, Shunjun Liu Yang, Qiaoling Lin, Zhijun Liu, Qianru Feng, Lin Ma, Mei Liu. Simultaneous Determination of Paeoniflorin, Albiflorin and Benzoylpaeoniflorin in Radix Paeoniae Alba by TLC. 2008. Chromatographia. Published electronically ahead of print.
- Shunjun Xu, Liu Yang, Runtao Tian, ZhengtaoWang, Zhijun Liu, Peishan Xie, Qianru Feng. Species differentiation and quality assessment of Radix Paeoniae Rubra (Chi-shao) by means of high-performance liquid chromatographic fingerprint. 2008. Journal of Chromatography A. Published electronically ahead of print.
- Yin, Jun, Aamir Zuberi, Zhanguo Gao, Dong Liu, Zhijun Liu, William T. Cefalu, Jianping Ye. 2008. Effect of Shilianhua extract and its fractions on body weight of obese mice. Metabolism Clinical and Experimental 57 (Suppl 1): S47-S51.
- William T Cefalu, Jianping Ye, Aamir Zuberi, David Ribnicky, Ilya Raskin, Zhijun Liu, Zhong Q Wang, Phillip J Brantley, Luke Howard and Michael Lefevre. 2008. Botanicals and metabolic syndrome. Am J Clin Nutr 87(suppl): 481S-7S.
- Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping. 2008. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 294: E148-E156.
- Liu, Dong, Joshua Schwimer, Zhijun Liu, Eugene Woltering, and Frank L. Greenway. 2008. Antiangiogenic effect of curcumin in pure versus in extract forms. Pharmaceutical Biology 46: 677-682.
- Guixin Chou, Shun-Jun Xu, Dong Liu, Gar Yee Koh, Jian Zhang, and Zhijun Liu. 2008. Quantitative and fingerprint analyses of Chinese sweet tea plant (Rubus Suavissimus S. Lee). Journal of Agricultural and Food Chemistry (accepted).
- Wedge, David; Klun, Jerome; Tabanca, Nurhayat; Demirci, Betul; Ozek, Temel; Baser, K. Husnu; Liu, Zhijun; Zhang, Sui; Cantrell, Charles; Zhang, Jian. 2008. Bioactivity-guided Fractionation and GC-MS Fingerprinting of Angelica sinensis and A. archangelica Root Components for Antifungal and Mosquito Deterrent Activity. Journal of Agricultural and Food Chemistry (accepted).
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: Numerous experiments have been conducted in the preparation of botanical extracts, fractionation, isolation, and structural elucidation. They were conducted for several projects with ultimate goals of identifying the bioactive compounds intrinsic in their residing extracts. The shilianhua (SLH) project focused on identifying bioactive compounds in the extract that contributed to the anti-diabetes activity. Additionally, this herbal extract showed anti-inflammatory effect. Bioassay-directed fractionation approach was taken that resulted in a potent fraction (F100), chromatographic fingerprint of which was generated. The research results have been reported in a manuscript accepted for publication. In a related research, ginger root extracts from several sources were prepared and analyzed for gingerol contents. Chromatographic fingerprinting methods were established and analyses for gingerols were conducted. The prepared ginger root extracts were investigated in cell cultures
for anti-diabetes evaluation. An animal study was also conducted to assess these extracts' ability to cause weight loss. These two research projects were funded by NIH and collaborated with the cell culture and animal labs at the Pennington Biomedical Research Center of the LSU System. The sweetgum fruit extract was another major research focus in 2007 collaboratively with the M.D. Anderson Cancer Center. This extract was found to possess potent cytotoxicity against a panel of human cancer cell lines, and was especially potent against human prostate cancer. Due to this discovery, fractionation was conducted to improve the potency. As a result of this fractionation, anti-cancer potency was increased by four fold. Chemical analyses revealed the compositional complexity of this refined extract was rich in triterpenes. These findings were used in two grant proposals (NIH and the Department of Defense) and in a provisional patent application. The Chinese sweet leaf tea was another research
focus later in the year as the NIH awarded an R21 to this PI. A series of fractionation steps were initiated and chromatographic fingerprinting method was established in LC/MS. This is a collaborative project with the LSU Health Sciences Center and the M.D. Anderson Cancer Center to investigate the leaf extract's antiangiogenic properties. Moreover, our research focus was placed on the collection of Louisiana native plants. As a result of this effort, 50 plant extracts primarily from Louisiana coastal regions, were prepared and evaluated for their anti-angiogenic activities in collaboration with the LSU Health Sciences Center, for their anti-obesity (via reduced food intake) properties with LSU Agricultural Center scientists, and for epigenome modulating activities with LSU Pennington Biomedical Research Center. Finally, our laboratory helped a local food company evaluate their decomposed food product (residue) that contained a bioactive compound. Thorough analyses and discussions we
were able to exploreoptions for adding value to their existing products.
PARTICIPANTS: Dr. Dong Liu, a natural product chemist, worked on the shilianhua and ginger projects. Dr. Guixin Chou, visiting professor from the Shanghai University of Traditional Chinese Medicine, worked on the analyses of the sweetgum fruit and the sweet leaf tea. Heather Kirk, a Ph.D. student in Renewable Natural Resources (RNR) worked on the screening of Louisiana plants for epigenome modulation activities. Gar Yee Koh, an M.S. student in RNR worked on the extraction and purification of the Chinese sweet leaf tea extract. Dr. Shunjun Xu, a post-doc in natural product analyses, worked on the analyses of Chinese sweet leaf tea with LC/MS instrumentation. These organizations and collaborators worked with the PI. LSU Pennington Biomedical Research Center: Frank L. Greenway, M.D., Tel. 225-763-2578, GreenwFL@pbrc.edu; Jianping Ye, M.D., Tel. 225-763-3163, yej@pbrc.edu; Kenneth J. Eilertsen, Ph.D., Tel.: 225-763-0275, Kenneth.Eilertsen@pbrc.edu; LSU Health Sciences Center in New
Orleans: Eugene A. Woltering, M.D., Tel. 504-464-8500, EWolte@lsuhsc.edu; LSU Agricultural Center: Roy J. Martin, Ph.D., Tel. 225-578-2284, RMartin@agcenter.lsu.edu; M.D. Anderson Cancer Center: Robert A. Newman, Ph.D., Tel. 713-563-7543,rnewman@mdanderson.org; Peiying Yang, Ph.D., Tel. 713-563-7531,pyang@mdanderson.org
TARGET AUDIENCES: Knowledge and information generated from this research project benefits a wide range of users, including other scientists, business investors, medical experts, and the general public. Our investigations will continue to inform the public about the health benefits of common foods and spices they consume. The proprietary technologies developed in my laboratory provide new opportunities for pharmaceutical and nutraceutical companies. Additionally, the skills and knowledge about fractionation and identification of bioactive compounds in botanical samples also helps small and/or existing companies assess the costs and efficiency of their current production methodologies.
Impacts
My laboratory currently focuses on the fractionation and analyses of numerous study agents. Our work has become an integral part of a research team that includes six research laboratories in the LSU System, and additional outside research laboratories. My laboratory contributes to the development of new products for several small companies, which lack in-house research capabilities. Proprietary technologies we have helped to create have resulted in numerous inquiries and discussions concerning potential license agreements. Current research in our laboratory has shown that shilianhua may not be effective in causing weight loss. However, the proprietary discovery that sweetgum fruit extract posses anti-cancer properties will, when further developed, likely add another, novel therapeutic method that can be used to battle cancer. These positive results will likely result in new start-up companies that will produce and market the extract. Our finding from research on the
ginger root will reveal and define health benefits of this common food and spice-like ingredient. Because of the multidisciplinary nature of my research involving both natural product chemistry and medical biology, skills enabling cross communication between fields of study have been developed. This unique development has resulted in multidisciplinary collaborations that are more efficient and productive.
Publications
- David A. York, Sonyja Thomas, Frank L. Greenway, Zhijun Liu, Jennifer C. Rood. 2007. The Effect of NT, an Herbal Supplement, on Body Weight in Rats. Chinese Medicine 2:10.
- Greenway, Frank L., Zhijun Liu, Ying Yu, Mary K. Caruso, Andrew Roberts, Joshua Schwimer, Alok K. Gupta, Drake Bellanger, Thomas Guillot, Eugene A. Woltering. 2007. An Assay to Measure Angiogenesis in Human Fat Tissue. Obesity Surgery 17: 510-515.
- Oner, F. Hakan, Yanno Bezerra, Gholam A. Peyman, Mandi D. Conway, James M. Lewis, Zhijun Liu, Frank Greenway, Eugene A. Woltering. 2007. Antiangiogenetic Effect of a Chinese Sweet Leaf Tea Extract in Experimental Corneal Neovascularization. Pharmaceutical Biology 45(1): 44-47.
- Andrew T. Roberts, Corby K. Martin, Zhijun Liu, Ronald J. Amen, Eugene A. Woltering, Jennifer C. Rood, Mary K. Caruso, Ying Yu, Hui Xie, Frank L. Greenway. 2007. The safety and efficacy of a dietary herbal supplement and gallic acid for weight loss. Journal of Medicinal Food 10(1): 184-188.
- Zhang, Jian,Ying Yu, Dong Liu, and Zhijun Liu. 2007. Extraction and composition of three naturally occurring anti-cancer alkaloids in Camptotheca acuminata seed and leaf extracts. Phytomedicine 14: 50-56.
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Progress 01/01/06 to 12/31/06
Outputs
This project continued its focus on the fractionation and identification of bioactive components in 2006 with a strong focus on antiangiogenic activities in plants. First, sweet leaf tea (Rubus suavissimus S. Lee) extract displaying potent antiangiogenic activity underwent fractionations. As a result, gallic acid was identified as one of the active compounds for the overall antiangiogenic activity of the extract (at least another compound was predicted). Further isolations are being made to identify these unknowns. Additionally, sweet leaf tea extract is being tested for its cancer preventative properties in tumor animal models bearing human cancer cells. Second, pomegranate fruit extract was discovered to have antiangiogenic components including gallic acid. Using gallic acid as a chemical marker, a highly concentrated (purified) pomegranate extract was achieved. The pomegranate extract is being subjected to fractionation and isolation towards characterization of
bioactive components. Third, antiangiogenic noni juice was subjected to bioassay directed fractionation and resulted in a highly concentrated noni juice extract. Characterization of this potent fraction revealed the presence of rutin and scopoletin. Activities of these compounds as well as identification of other compounds are ongoing. Concurrently, this highly concentrated noni juice extract may be the subject of clinical investigations to be sponsored through a license to Pacific Biotech LLC. Fourth, a standardized black raspberry extract that retained all the angiogenic inhibitors - likely three - was developed in order to reach a potent dose for animal studies that tested the hypothesis of whether blocking new blood vessel growth worked in tumor-bearing animals. It was found that the antiangiogenic black raspberry extract was effective in retarding tumor growth and extending lifespan by 30% longer. The fact that oral administration was effective supports the use of black raspberry
extract as a potential dietary supplement in the prevention and treatment of cancer. Fifth, fractionation of a traditional Chinese plant (SLH) was performed to identify responsible compounds for the observed benefits in relieving metabolic syndrome (insulin resistance). It was found that SLH controlled fatty acid and glucose metabolism by stimulating energy expenditure and insulin action. Currently, the class of flavonoids was the target of isolation. This is a collaborative project in a center grant (lead institution: LSU Pennington Biomedical Research Center). Sixth, continued collaborations with Dr. David Wedge at USDA ARS resulted in the identification of three plant extracts that had activities against Colletotrichum fungal species. Seventh, a grant from Phoenix Biotechnology showed that the anti-cancer oleandrin levels varied significantly with season, stressing the importance of understanding the plant chemistry to gain a maximum opportunity in designing harvesting regimens.
Eighth, collaboration with Dr. Kenneth Eilertsen of the Pennington Stem Cell Laboratory resulted in a list of potential 'hits' plant and additional confirmation is being undertaken.
Impacts
Food and human nutrition industries are looking for candidate functional food products. Finding bioactive components is one of the most challenging tasks in terms of science, time, and money. Identifying bioactive components in plants and especially in agricultural and horticultural crops is the essence of this project. The LSU AgCenter has the expertise in developing functional food products once the bioactive components are identified through interdisciplinary collaborations. Bioactive components based functional food products have very broad applications, ranging from new and improved food technologies to dietary supplements, and healthier botanical products. Diverse populations will be impacted by this research. For example, people with diabetes, obesity, and cancer could see science based products at affordable prices contributing to their plans for maintaining health.
Publications
- Zhu, Bin, Qingbiao Wang, Esben F. Roge, Peng Nan, Zhijun Liu, and Yang Zhong. 2006. Chemical variation in leaf oils of Pistacia chinensis from five locations in China. Chemistry of Natural Products. 42(4): 422-425.
- Liu, Zhijun, Joshua Schwimer, Dong Liu, James Lewis, Frank L. Greenway, David A. York, and Eugene A. Woltering. 2006. Gallic acid is partially responsible for the anti-angiogenic activities of Rubus leaf extract. Phytotherapy Research 20(9): 806-813.
- Greenway, Frank L., Zhijun Liu, Corby K. Martin, Wei Kai-yuan, James Nofziger, Jennifer C. Rood, Ying Yu, and Ronald J. Amen. 2006. Safety and Efficacy of NT, an Herbal Supplement, in Treating Human Obesity. International Journal of Obesity April 25: 1-5.
- Zhao, Jiayuan, Jimei Liu, Xiaoyan Zhang, Zhijun Liu, Tashi Tsering, Yang Zhong, and Peng Nan. 2006. Chemical Composition of the Essential Oils of Three Wild Bergenia Species from Western China. Flavour and Fragrance Journal 21: 431-434.
- Liu, Jimei, Peng Nan, Qiong Tsering, Tashi Tsering, Zhankui Bai, Li Wang, Zhijun Liu, and Yang Zhong. 2006. Volatile constituents of the leaves and flowers of Salvia przewalskii Maxim. from Tibet. Flavour and Fragrance Journal 21: 435-438.
- Wang, Qingbiao, Yong Yang, Xiaomin Zhao, Bin Zhu, Peng Nan, Jiayuan Zhao, Li Wang, Fan Chen, Zhijun Liu, and Yang Zhong. 2006. Chemical variation in the essential oil of Ephedra sinica from Northeastern China. Food Chemistry 98: 52-58.
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Progress 01/01/05 to 12/31/05
Outputs
Modern laboratory studies have confirmed the benefits and possible modes of action of botanical extracts for human healthcare, but turning them into practical treatments faces two major obstacles, both typical in the use of botanical extracts for healthcare and therapeutics. First, the botanical extracts are not standardized with reference to the active ingredients. Manufacturing without knowledge of what is responsible in the apparent active botanical extracts risks the loss of the key ingredients in the process and results in inconsistent clinical effects. Second, underdosing may have been a major problem in observing clinical effects of many promising botanical extracts observed in laboratory studies. In 2005, the following were accomplished. (1) Scientists from LSU campuses collaborated to fractionate and isolate antiangiogenic agents from several botanical extracts. One of the angiogenic inhibition applications is to suppress the growth of tumors, which require
the formation of new blood vessels to supply the needed nutrients and oxygen. My lab applied column chromatography techniques in the isolation, and labs at the Health Sciences Center in New Orleans and Pennington Biomedical Research Center provided assay support to direct the isolation process. (2) My lab developed a standardized protocol for black raspberry extract using an active chemical marker, and manufactured back raspberry extract with this protocol. This standardized berry extract was preliminarily tested at the LSU Health Sciences Center in a tumor-bearing rat model (human pancreatic carcinoma) and was found to inhibit tumor growth and provide a 30% longer lifespan during the 28 day study. (3) A Chinese blackberry leaf tea extract was standardized and manufactured in my lab, and the standardized leaf extract was tested for safety in a pilot human trial by Dr. Eugene Woltering at the LSU Health Sciences Center. Twelve subjects were enrolled in the study based on an approved
Institutional Review Board protocol. After almost 6 months of ingesting the leaf extract at a dose of 12 capsules per day, none complained of side effects to their doctors, indicative of good safety. (4) My lab developed a 'Super Noni' technology, by which the noni fruit's antiangiogenic ingredients were concentrated 100 fold. This 'Super Noni' extract was manufactured and tested in a rodent model for absorption and safety. 'Super Noni' fruit extract was safe and had satisfactory absorption properties through oral routes. (5) I collected and extracted eight Louisiana native salt marsh plants. Extracts from these plants were tested against five fungal species in cell cultures at two USDA research laboratories (Dr. David Wedge at the Natural Product Utilization Unit at Oxford, MS and Dr. Anthony De Lucca at the Southern Regional Research Center in New Orleans). One of the extracts was found to be fungicidal and round-one fractionation separated the fungicidal activities into
concentrated fractions. (6) Fifty plant extracts were prepared in my lab and was sent to Dr. Kenneth Eilertsen of the Pennington Stem Cell Laboratory to test for major anti-cancer activities.
Impacts
Overcoming the quality control and underdosing issues of botanical extracts is likely to result in successful clinical results. The 'Super Noni' technology, for example, is currently being considered for technology transfer. If finalized, this technology will enter the product development pipeline by the company. Successful launch of this product will not only create business opportunities but also help millions of cancer survivors who need better tools to manage cancer.
Publications
- Xiaojun Wu, Dong Liu, Zhijun Liu. Establishment of a hairy root culture system for producing anti-hypertensive Eucommia extract. Abstract submitted for the American Society of Pharmacognosy meeting, Corvallis Oregon, July 22-27, 2005.
- Liu, Dong, Joshua Schwimer, Eugene Woltering, Zhijun Liu. Antiangiogenic effect of curcumin in pure versus in extract forms. Abstract submitted for the American Society of Pharmacognosy meeting, Corvallis Oregon, July 22-27, 2005.
- Andrew T. Roberts, Mary K. Caruso, Ying Yu, Eugene A. Woltering, Zhijun Liu, Joshua E. Schwimer, Drake E. Bellanger, Thomas S. Guillot, and Frank L. Greenway. VALIDATION OF AN ANGIOGENESIS ASSAY BASED ON HUMAN FAT TISSUE. Abstract at the NAASO's 2005 Annual Scientific Meeting.
- Liu, Zhijun, Conrad Hornick, and Eugene Woltering. 2005. Noni tree: potential cancer preventative, therapy. Louisiana Agriculture 48 (1): 8-9.
- Lang, Cynthia, Zhijun Liu, H.Wayne Taylor, and David G. Baker. 2005. Effect of Eucommia ulmoides on Systolic Blood Pressure in the Spontaneous Hypertensive Rat. American Journal of Chinese Medicine 33(2): 215-230.
- Li, Zhanhai and Zhijun Liu. 2005. Camptothecin production in Camptotheca acuminata hydroponic culture and nitrogen enrichments. Canadian Journal of Plant Science 85: 447-452.
- Qiong WU, Da-Xu FU, Ai-Jun HOU, Guang-Qing LEI, Zhijun Liu, Jia-Kuan CHEN, and Tong-Shui ZHOU. 2005. Antioxidative Phenols and Phenolic Glycosides from Curculigo orchioides. Chem. Pharm. Bull. 53(8): 1065-1067.
- Liu, Dong, Zhanguo Gao, Jian Zhang, Jianping Ye, and Zhijun Liu. 2005. Bioassay-guided fractionation of the Rubus suavissimus leaf extracts possessing NF-Kappa-B inhibitory activities and a separable cytotoxicity. Pharmaceutical Biology 43(8): 713-717.
- Liu, Zhijun, Joshua Schwimer, Dong Liu, Frank L. Greenway, Catherine T. Anthony, and Eugene A. Woltering. 2005. Black Raspberry Extract and Fractions Contain Angiogenesis Inhibitors. Journal of Agriculture and Food Chemistry 53(10):3909-3915.
- Z Li, Z Liu. 2005. Plant regeneration from leaf petiole in Camptotheca acuminata. In Vitro Cellular and Developmental Biology - Plant 41(3):262-265.
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