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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 12, No. 5, 2013, pp. 691-698
Bioline Code: pr13084
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 12, No. 5, 2013, pp. 691-698

 en Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate Cells via JAK2-STAT3 Pathway to Protect against Hepatic Fibrosis
Wei, Yanfei; Zhao, Tiejian; Zhang, Zhiwei; Liu, Xuemei; Huang, Zhenqing; Zhang, Yuan & Li, Jingqiang

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

 
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