Resveratrol Suppresses Hepatic Stellate Cells Activation Through Blocking NF-KB And Pi3K/Akt Signaling Pathway

Objective:In this study, Resveratrol (Restrol) was investigated whether Restrol reverse hepatic fibrosis, and also research its the effects to hepatic fibrosis.Methods:In the present study, we investigated Restrol treatment protected against lipopolysaccharide (LPS)-induced cytotoxicity in an immortalized rat hepatic stellate cell line(T-HSC/Cl-6). T-HSC/C1-6cells were treated with Restrol (0,3.125,6.25and12.5μM) prior to LPS (1μg/ml).T-HSC/Cl-6cells proliferation were estimated by MTT assay. The cells were seeded in100mm culture dishes at a density of1×106cells per dish. T-HSC/Cl-6cells were treated with Restrol (3.125,6.25and12,5μM) prior to LPS (1μg/ml) for24h. Then western blotting analysis were applied to detect a-smooth muscle actin (a-SMA), type I collagen (Collagen I) Phosphoinositide-3kinase (p-PI3K), Akt, PI3K, NF-κB, MyD88TLR4SHP-1, AMPK, LXR-a and LXR-β protein levels. The cells were pretreated with indicated same concentration of Restrol in different time.Results:The data demonstrated Restrol effectively decreased activated T-HSC/C1-6cells viability. The expression of a-SMA, Collagen-I and expression in protein levels decreased after Restrol treatment in T-HSC/Cl-6cells. Meanwhile, Restrol significantly attenuated the express of toll-like receptor4(TLR4) and Myd88. The expression of phosphatidylinositol3-kinase (PI3K) and serine threonine kinase B (Akt) phosphorylation were significantly decreasd by Restrol. Restrol significantly attenuated the express of SHP-1and increased P-AMPK. Restrol significantly attenuated the express of LXR-a and increased LXR-β.Conclusion:In this study, we have shown that Restrol attenuates Hepatic fibrosis partially via blocking NF-κB transcription and PI3K phosphorylation on the activated T-HSC/Cl-6cells. Restrol would be a potential therapeutic medicine for the patients with liver fibrosis.