Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate Cells via JAK2-STAT3 Pathway to Protect against Hepatic Fibrosis

Yanfei Wei¹, Tiejian Zhao¹ , Zhiwei Zhang², Xuemei Liu¹, Zhenqing Huang¹, Yuan Zhang¹, Jingqiang Li¹

¹Department of Physiology, Guangxi University of Chinese Medicine, 179# East Mingxiu Road, Nanning, Guangxi, 530001; ²Ruikang Hospital, Guangxi University of Chinese Medicine, Nanning, 10#, Huadong Road, Guangxi 530021, PR China.

For correspondence:- Tiejian Zhao Email: zhaotiejian@163.com Tel:+867712214279

Received: 22 July 2013 Accepted: 7 July 2013 Published: 18 October 2013

Citation: Wei Y, Zhao T, Zhang Z, Liu X, Huang Z, Zhang Y, et al. Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate Cells via JAK2-STAT3 Pathway to Protect against Hepatic Fibrosis. Trop J Pharm Res 2013; 12(5):691-698 doi: 10.4314/tjpr.v12i5.5

© 2013 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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). Leptin-induced 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.

Keywords: Plumbagin, Leptin, Hepatic stellate cell, Proliferation, Signal transduction pathway, Anti-inflammatory