Morin ameliorates chemically induced liver fibrosisin vivoand inhibits stellate cell proliferationin vitroby suppressing Wnt/β-catenin signaling


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Abstract

The anti-fibrotic effect of morin was examined in LX-2 cells (culture-activated human hepatic stellate cells) and in diethylnitrosamine induced rat model of liver fibrosis. The in vitro study was designed to determine whether morin affects the survival of cultured LX-2 cells, while the in vivo study was designed to evaluate the antioxidant and anti-fibrotic efficacy of morin on diethylnitrosamine induced liver fibrosis in male albino Wistar rat. The activities of liver function enzymes in serum, liver lipid peroxide levels, activities of serum antioxidant enzymes and liver architecture were monitored to cast light on the antioxidant and hepatoprotective nature of morin. To establish the anti-fibrotic effects of morin, the levels of key Wnt signaling molecules which are strongly associated with the signal transduction pathway of HSC activation were measured. Overall, from the in vitro results, it was observed that morin at 50 μM concentration inhibited the proliferation of cultured LX-2 cells, inhibited Wnt signaling and induced G1 cell cycle arrest. The in vivo results further confirmed that morin by downregulating the expressions of GSK-3β, β-catenin and cyclin D1 ameliorated DEN-induced liver fibrosis. Hence morin could be employed as a promising chemopreventive natural supplement for liver fibrosis.HighlightsIn vivo and in vitro results revealed the active participation of Wnt signaling.Morin at 50 μM inhibited LX-2 cell proliferation by suppressing Wnt signaling.Morin exhibited hepatoprotective effects against DEN induced liver fibrosis.Morin inhibited HSC activation in vivo by downregulating Wnt/β-catenin signaling.

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