Abstract Title:

Genistein attenuates D-GalN induced liver fibrosis/chronic liver damage in rats by blocking the TGF-β/Smad signaling pathways.

Abstract Source:

Chem Biol Interact. 2016 Nov 19 ;261:80-85. Epub 2016 Nov 19. PMID: 27876602

Abstract Author(s):

Ajaz Ahmad Ganai, Mohammad Husain

Article Affiliation:

Ajaz Ahmad Ganai


BACKGROUND AND AIM: Genistein is a major isoflavonoid abundantly found in soy. Earlier genistein has been reported to possess protective effect against a multitude of disorders including cancer. Previously we demonstrated the protective effects of Genistein in d-Galactosamine (D-GalN) induced fulminant hepatic failure (FHF) in rats. In present study, we evaluated the hepatoprotective activity of Genistein in rat model of chronic liver damage and liver fibrosis.

METHODS: Liver fibrosis was induced by intraperitoneal injection of D-GalN (250 mg/kg BW) twice a week for 12 weeks. Genistein (5 mg/kg BW) was given via intra-gastric route as co-treatment daily for 12 weeks.

RESULTS: Genistein co-treatment significantly attenuated D-GalN-induced chronic liver damage and liver fibrosis as evident from a significant amelioration in functional impairment, including inhibition of the activation of Hepatic stellate cells (HSC), decreased expression in alpha smooth muscle actin (α-SMA) and accumulation of collagen matrix, and an elevation in serum alanine transaminase (ALT) and aspartate transaminase (AST) level. In addition Genistein co-treatment was associated with elevated expression of hepatic Smad7, which ultimately blunts the expression of TGF-β and the activation of TGF-β/Smad signaling. Furthermore Genistein significantly prevented the histopathological changes induced by D-GalN.

CONCLUSION: Our results suggest that Genistein could be a novel therapeutic/nutraceutical agent in treating chronic liver damage and liver fibrosis. In addition our study also suggests a possible mechanism of action in which Smad7-induced inhibition of TGF-β/Smad2/3 can be a central mechanism by which Genistein protects liver from chronic injury.

Study Type : Animal Study

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