Research

Latest Research Developments

08/24/10: Health Benefits from Tea: Perception vs. Reality

WellGen’s own Dr. Shiming Li presented research about the analytical method for measuring polyphenols and the polyphenol content in ready-to-drink tea beverages at the American Chemical Society (ACS) meeting that began August 22 [...]

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Nutrigenomics

Nutrigenomics is the study of the effects of nutrients and dietary ingredients on gene expression. Nutrigenomics is a powerful discovery tool that enables WellGen to identify candidate nutraceuticals with strong anti-inflammatory potential

Inflammation is regulated by a complex biological cascade. WellGen’s research employs a multi-gene approach to discovery which more closely resembles what happens in nature.

Whereas traditional pharmaceutical developers try to identify a single point of intervention, WellGen science focuses on a number of genes which control the human inflammatory processes.

Nutrigenomics is the study of how food and food constituents influence the way our genes (DNA) are translated, via RNA, into the proteins that make up our bodies. WellGen’s nutrigenomics is based on our founding patent and over 10 years of expertise. WellGen’s approach, which targets the inflammatory cascade through modulation of multiple genes, using products with a history of use as foods, is both more biologically rational and inherently safer than the pharmaceutical industry approach.

For the primary nutrigenomic screening, a cell-based in vitro model for inflammation is used. In response to injury or infection, cells called monocytes are attracted to the site of injury and differentiate into macrophages. During differentiation, various inflammatory genes are induced and pro- and anti-inflammatory proteins (‘cytokines’ and ‘chemokines’) are released which trigger a cascade of cellular activities to both protect and promote repair. WellGen has developed and patented a proprietary screening platform that employs human monocytes treated chemically to induce differentiation in the presence of absence of a natural product or extract. Based on a carefully selected set of genes that represent key steps in the inflammatory cascade, we are able to evaluate the impact of each product on the inflammatory process in these cells. The influence of these products on the profile of gene expression is used to evaluate the potential for each lead to exhibit a therapeutic anti-inflammatory benefit in a disease state. Promising leads are then further evaluated in animal models before being tested in clinical trials.

Selected articles about WellGen nutrigenomics platform and pipeline:
Dushenkov, S and Evans, D. Review: Phenolics, inflammation and nutrigenomics. Journal of the Science of Food and Agriculture. December 2006: 86, 2503-2509.

Ghai G, et al. (WellGen, Inc./Rutgers Univ.) Methods of screening foods for nutraceuticals. U.S. Patent # 5,955,269.

Müller M, Kersten S. Nutrigenomics: goals and strategies Nat Rev Genet. 2003 Apr;4(4):315-22.

van Ommen B, Stierum R. Nutrigenomics: exploiting systems biology in the nutrition and health arena. Curr Opin Biotechnol. 2002 Oct;13(5):517-21.

Eguchi A, Murakami A, Li S, Ho CT, Ohigashi H. Suppressive effects of demethylated metabolites of nobiletin on phorbol ester-induced expression of scavenger receptor genes in THP-1 human monocytic cells. Biofactors. 2007;31(2):107-16.

Evans, D. Why Nutrigenomics is a Reality – Starting Now – for the Global Food Industry. Nutraceutical Business & Technology. Volume 2 Number 4 Sept/Oct 2006, p.46-51

Hirsch, J. B. and Evans, D. The State of Nutrigenomics. Nutraceuticals World. September 2005: 56-59

Hirsch, J. B. and Evans, D, Beyond Nutrition: The Impact of Food on Genes. Food Technology, 2005, 59(7):24-33

Ho C-T, et al. Hydroxylated polymethoxyflavone compositions. U.S. Published Patent Application # 2007-0275106. (reports use of hydroxylated polymethoxyflavones for reducing severity of inflammatory responses).

Ho C-T, et al. Benzotropolone derivatives and modulation of inflammatory response. U.S. Patent #s 7,087,790 and 7,288,680.

Ho C-T, et al. Bioactive compounds and methods of uses thereof. U.S. Patent # 7,351,739. (reports compositions derived from Rabdosia rubescens and their use treating cancerous cells).

Lai, C-S; Li, S.; Chai, C-Y.; Lo, C-Y.; Dushenkov, S.; Ho, C-T.; Pan, M-H.; Wang, Y-J. anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3′,4′-didemethylnobiletin, derived from nobiletin, Carcinogenesis, 2008, 29(12), 2415-2424.

Lai C-S.; Li, S.; Chai C-Y.; Lo C-Y.; Ho C-T; Wang Y-J.; Pan M-H. 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，2007 , 28, 2581-2588

Li, S.; Pan, M-H.; Lo, C-H.; Tan, D.; Wang, Y. Shahidi, F.; Ho, C-T. Chemistry and health effects of polymethoxyflavones and hydroxylated polymethoxyflavones, J. Functional Food, 2009, 1 (1), 2-12.

Li S, Pan MH, Lai CS, Lo CY, Dushenkov S, Ho CT. Isolation and syntheses of polymethoxyflavones and hydroxylated polymethoxyflavones as inhibitors of HL-60 cell lines. Bioorg Med Chem. 2007 May 15;15(10):3381-9. Epub 2007 Mar 13.

Li, S.; Pan, M-H.; Wang, Z.; Lambros, L.; Ho, C-T. Biological activity, metabolism and separation of polymethoxyflavonoids from citrus peels, Tree and Forestry Science and Biotechnology, 2008, 2 (Special Issue 1), 36-51. (invited review)

Li S, Sang S, Pan MH, Lai CS, Lo CY, Yang CS, Ho CT. Anti-inflammatory property of the urinary metabolites of nobiletin in mouse. Bioorg Med Chem Lett. 2007 Sep 15;17(18):5177-81. Epub 2007 Jul 7.

Lucas-Schnarre P. Nutrigenetics and Nutrigenomics. May 2008. http://www.nutraceuticalsworld.com/articles/2008/05/nutrigenetics-nutrigenomics

Lucas-Schnarre P. Nutrigenomics: A Discovery Tool for Ingredients Old and New. Nutrition Business Journal. Dec. 1, 2005.

McKeever KH, et al. Compositions and methods for optimizing exercise recovery. U.S. Published Patent Application # 2007-0042972. (reports use of polymethoxyflavones from orange peel extract in method)

Rosen R T. Anti-inflammatory cranberry flavonol extract preparations. U.S. Patent # 7,270,837.

Sergeev IN, Ho CT, Li S, Colby J, Dushenkov S. Apoptosis-inducing activity of hydroxylated polymethoxyflavones and polymethoxyflavones from orange peel in human breast cancer cells. Mol Nutr Food Res. 2007 Dec;51(12):1478-84.

Sergeev IN, Li S, Ho CT, Rawson NE, Dushenkov S. Polymethoxyflavones activate Ca2+-dependent apoptotic targets in adipocytes. J Agric Food Chem. 2009 Jul 8;57(13):5771-6.

Sergeev I. N.; Sergeev; Colby J.; Ho C-T. Dushenkov S. Polymethoxylated flavones induce Ca2+-mediated apoptosis in breast cancer cells, Life Sciences, 2006 , 80, 245-253.

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 cancer cells by apoptosis, Mol. Nutr. Food Res. 2009, 53, 398 – 406

Clinical support for WellGen^® theaflavin- rich black tea concentrate:

Human Clinical Study 1:

Systemic Inflammation Study LPS (lipopolysaccharide)- mediated challenge exposes the inflammation cascade and is a fundamental pharmaceutical inflammation probe.

Key findings

Reduces expression of pro-inflammatory mRNA and cytokines/chemokines proteins
Inflammatory biomarker levels ranging between two-to-four fold less than the placebo group
Elevation of immuno-modulatory cytokine IL-10

Human Clinical Study 2:

Exercise-induced Inflammation - Test the effects in high-intensity anaerobic exercise on:

Delayed onset muscle soreness (DOMS)
Oxidative stress
Cortisol response
Inflammatory biomarkers