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  • Title: Effect of salvianolic-acid B on inhibiting MAPK signaling induced by transforming growth factor-β1 in activated rat hepatic stellate cells.
    Author: Lv Z, Song Y, Xue D, Zhang W, Cheng Y, Xu L.
    Journal: J Ethnopharmacol; 2010 Nov 11; 132(2):384-92. PubMed ID: 20599490.
    Abstract:
    AIM OF THE STUDY: Salvianolic-acid B (SA-B) is an effective component of Radix Salviae miltiorrhizae for anti-hepatic fibrotic herbs. MAPK signaling pathway has been implicated in hepatic stellate cells (HSC) stimulated by TGF-(1. We have investigated the effect of SA-B on MAPK pathway in rat HSC. MATERIALS AND METHODS: To observe the pharmacological effect of SA-B on HSC, SA-B was added into the medium of primary HSC. TGF-(1 was added during last 2h, and PD98059 (ERK inhibitor) and SB203580 (p38 inhibitor) were added just 30 min before adding TGF-(1. MEF2 and Col. I were measured by luciferase reporter gene assay and Western blot. (-SMA, MEF2, Raf, ERK, p-ERK, MEK, p-MEK, p38, p-p38, MKK3 and p-MKK3/6 were assayed by Western blot. Activity of MMP-2 and MMP-9 was analyzed by zymography. Each experiment was repeated for three times. RESULTS: The expression of (-SMA and Col. I in HSC was inhibited by SA-B. There was no effect of SA-B on the activity of MMP-2 or MMP-9 in the media of cultured HSC. Phosphorylation of ERK1/2 in HSC stimulated with or without TGF-(1 was inhibited by SA-B. Specifically, phosphorylation of MEK (upstream kinase of ERK pathway) was inhibited by SA-B. SA-B also inhibited phosphorylation of MKK3/6 (upstream kinases of p38 pathway) and inhibited the synthesis of MEF2. CONCLUSIONS: SA-B performs anti-hepatic fibrosis through inhibiting ERK and p38 MAPK pathway in HSC. SA-B inhibits ERK pathway via inhibiting phosphorylation of MEK and inhibits p38 MAPK pathway via blocking phosphorylation of MKK3/6 and inhibiting expression of MEF2 in HSC with or without TGF-(1 stimulation.
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