Fisetin alleviates thioacetamide-induced hepatic fibrosis. - GreenMedInfo Summary
Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/β-catenin signaling pathway.
Immunopharmacol Immunotoxicol. 2022 Mar 8:1-12. Epub 2022 Mar 8. PMID: 35255766
Amany A El-Fadaly
BACKGROUND: Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem.
OBJECTIVE: The current study endeavored to investigate the repressing effect of fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats.
MATERIALS AND METHODS: Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, β-catenin, glycogen synthase kinase 3 (GSK-3β) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed.
RESULTS: Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor β1 (TGF-β1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased β-catenin and increased GSK-3β levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1.
CONCLUSION: Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferationsuppressing the Wnt/β-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.