Therapeutic efficacy of Ganoderma Lucidum on Thioacetamide-Induced Hepatic Fibrosis through Inhibition of TGF-β1 signaling in Male Rats.

Document Type : Original Article

Authors

1 Pharmacology and Biochemistry, Faculty of pharmacy Delta University for science and Technology. International Costal Road, Gamasa City, Mansoura, Dakhliya, Egypt.

2 Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, International Costal Road, Gamasa City, Mansoura, Egypt. Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

Abstract

The anti-fibrosis efficacy of Ganoderma lucidum (GL) was investigated on thioacetamide (TAA)-induced liver fibrosis. Experimental fibrosis was induced by (200 mg/kg TAA, i.p.) twice weekly for 6 weeks in male Sprague-Dawley rats. GL was administered to TAA rats, either as (250/500 mg/kg, i.p) daily for further 3 weeks. Repeated administration of TAA caused liver fibrosis evidenced by significant elevation of hepatic TGF-β1 accompanied by an increase in the hydroxyproline content, oxidative stress levels and liver biomarkers. Contrarily, GL treatment significantly reduced ALT, AST, total bilirubin, MDA, NO concentrations and restored SOD activity. H & E and Masson trichrome staining confirmed that GL suppressed liver fibrosis, inflammation and attenuated the histopathological alterations. GL also elicited a statistical decrease in TGF-β1 level and hydroxyproline content with a concomitant decline in NFk-B and α-SMA immunoexpression in the TAA treated rats. Furthermore, GL downregulated TNF-α and IL-1β levels in TAA-treated rats compared to the control group. Conclusion: GL possesses a pronounced protective activity against TAA-induced fibrosis in rats; It significantly inhibits oxidative stress, inflammation and diminishes fibrosis by: inhibiting NFk-B activation, reducing TGF-β mediated by PI3K-AKT pathway thus restoring the liver function, the effect was in a dose dependent manner.

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