Plumbagin inhibits leptin-induced proliferation of hepatic stellate cells via JAK2-STAT3 pathway to protect against hepatic fibrosis

Abstract

Purpose: To investigate the protective effects of plumbagin against liver fibrosis and explore the influence of plumbagin on the proliferation of hepatic stellate cells (HSCs). Methods: HSC-LX2 cells were divided into blank/control group, 100 ng/ml leptin group, 100 ng/ml leptin + 2 μmol/L plumbagin group, 100 ng/ml leptin + 8 μmol/L plumbagin group and 100 ng/ml leptin + 6.25 μg/ml colchicines group. The expressions of leptin receptor protein (OB-Rb), p-JAK2, p-STAT3, JAK2, STAT3, p- ERK1/2, ERK1/2 and MMP-1 were detected by Western blot assay. The content of type I collagen in the supernatant of HSCs was also measured after stimulation by leptin. Results: Leptin induced OB-Rb expression in HSCs, which reached a peak level at 24 h (p < 0.01). Leptininduced OB-Rb expression was significantly inhibited by plumbagin at concentrations of 2 μmol/L and 8 μmol/L, respectively. Western blot assay revealed that plumbagin significantly decreased pJAK2 expression in leptin-treated HSCs (p < 0.01). Leptin induced expression of pSTAT3 significantly decreased after plumbagin treatment in HSC-LX2 (p < 0.01). p-ERK1/2 expression markedly decreased in plumbagin-treated HSCs (p < 0.01). Plumbagin significantly increased MMP-1 expression in leptin-treated HSCs (p < 0.01). Conclusion: Plumbagin has an anti-fibrotic effect and may decrease the protein expressions of components in JAK2-STAT3 pathway to inhibit HSC proliferation. Thus, plumbagin may be useful in the clinical prevention and treatment of liver fibrosis. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.