Soy-derived phytoalexins: mechanism of in vivo biological effectiveness in spite of their low bioavailability
- 48 Downloads
The well-demonstrated bioefficacy of phytochemicals in spite of their paradoxically low bioavailability has long puzzled scientists. Glyceollins, a family of soy-derived phytoalexins, have been reported to exert a variety of biological effects in vitro and in vivo systems in spite of poor systemic bioavailability after oral administration, suggesting that secondary messengers generated in gastrointestinal tract would transfer signals to target organs and tissues to manifest any effect. This review focuses on the potential mechanisms of how the poorly bioavailable glyceollins could still exert in vivo biological effects.
KeywordsPhytochemicals Nrf2 Heme oxygenases Carbon monoxide Glyceollins
This work was supported by the National Research Foundation (NRF) of Korea, funded by the Ministry of Science and ICT (MSIT), Republic of Korea (Grant No. 2017R1A2B4005087).
- Burow ME, Boue SM, Collins-Burow BM, Melnik LI, Duong BN, Carter-Wientjes CH, Li S, Wiese TE, Cleveland TE, McLachlan JA. Phytochemical glyceollins, isolated from soy, mediate antihormonal effects through estrogen receptor alpha and beta. J. Clin. Endocrinol. Metab. 86: 1750–1758 (2001)Google Scholar
- Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 14: 120–125 (2005)Google Scholar
- Gres MC, Julian B, Bourrie M, Meunier V, Roques C, Berger M, Boulenc X, Berger Y, Fabre G. Correlation between oral drug absorption in humans, and apparent drug permeability in TC-7 cells, a human epithelial intestinal cell line: Comparison with the parental Caco-2 cell line. Pharm. Res. 15: 726–733 (1998)CrossRefGoogle Scholar
- Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. An Nrf2 small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236: 313–322 (1997)CrossRefGoogle Scholar
- Kim BR, Hu R, Keum YS, Hebbar V, Shen G, Nair SS, Kong AN. Effects of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by sulforaphane. Cancer. Res. 63: 7520–7525 (2003)Google Scholar
- Kobayashi M, Li L, Iwamoto N, Nakajima-Takagi Y, Kaneko H, Nakayama Y, Eguchi M, Wada Y, Kumagai Y, Yamamoto M. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol. Cell. Biol. 29: 493–502 (2009)CrossRefGoogle Scholar
- Maines MD, Trakshel GM, Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J. Biol. Chem. 261: 411–419 (1986)Google Scholar
- Nozawa K, Kawabata-Shoda E, Doihara H, Kojima R, Okada H, Mochizuki S, Sano Y, Inamura K, Matsushime H, Koizumi T, Yokoyama T, Ito H. TRPA1 regulates gastrointestinal motility through serotonin release from enterochromaffin cells. Proc. Nat. Acad. Sci. USA 106: 3408-3413 (2009)CrossRefGoogle Scholar
- Quadri SS, Stratford RE, Boue SM, Cole RB. Identification of glyceollin metabolites derived from conjugation with glutathione and glucuronic acid in male ZDSD rats by online liquid chromatography-electrospray ionization tandem mass spectrometry. J. Agric. Food Chem. 62: 2692–2700 (2014)CrossRefGoogle Scholar
- Salvo VA, Boue SM, Fonseca JP, Elliott S, Corbitt C, Collins-Burow BM, Curiel TJ, Srivastav SK, Shih BY, Carter-Wientjes C, Wood CE, Erhardt PW, Beckman BS, McLachlan JA, Cleveland TE, Burow ME. Antiestrogenic glyceollins suppress human breast and ovarian carcinoma tumorigenesis. Clin. Cancer Res. 12: 7159–7164 (2006)CrossRefGoogle Scholar