BIOLOGICAL EFFICACY, MECHANISMS OF ACTIONS OF SOY-DERIVED PHYTOALEXIN GLYCEOLLINS IN PREVENTION OF CHRONIC DISEASES

Abstract

Cardiovascular disease (CVD) is the leading cause of deaths worldwide. Prostate cancer is the most prevalent cancer in U.S. male population. Diet-induced hypercholesterolemia and chronic inflammation promote the development of both CVD and prostate cancer. Glyceollins are a group of soy phytoalexins possessing a variety of biological activities. This research project focused on characterizing glyceollins' bioactivities in alleviating cholesterol dysregulation, prevention of prostate cancer, and regulating gut microbiome. The first part of the project aimed to evaluate glyceollins' cholesterollowering effect in-vivo. Male golden Syrian hamsters were fed high-fat diet with or without glyceollins supplementation for 28 days. Glyceollins supplementation led to a significant reduction of plasma VLDL, hepatic cholesterol esters and total lipid content. Consistent with changes in circulating cholesterol, glyceollins supplementation also altered expression of the genes related to cholesterol metabolism in the liver. The second part of the study aimed to evaluate glyceollins' effect in reducing prostate cancer tumor growth in a xenograft model. An initial delayed appearance of tumor was observed in a PC-3 xenograft model. However, no difference in tumor sizes was observed in a LNCaP xenograft model. Extrapolation analysis of tumor measurements indicated that no difference in sizes was expected for both PC-3 and LNCaP tumors. Glyceollins had no effect on the androgen responsive pathway, its proliferation, cell cycle, or on angiogenesis genes in tumor and xenobiotic metabolism, cholesterol transport, and inflammatory cytokine genes in liver. Glyceollins' low bioavailability might have led to the ineffectiveness in reducing tumor growth in-vivo. The microbiome has emerged as an important and integral part of the human physiology with a significant role in human health and disease. The third part of the study aimed to evaluate the effect of glyceollins on the gut microbiome in mice. Fecal and cecal samples collected from mouse feeding studies were analyzed for microbial population and composition. Glyceollins supplementation did not alter gut bacteria groups in cecal sample examined in this study. Glyceollins significantly affected total Enterobacteriaceae and Ruminococcus population in fecal samples collected at 24 h, indicating the impact and importance of time of collection in interpreting gut microbiome data in fecal analysis.