Antiproliferative effect of salvianolic acid A on rat hepatic stellate cells

Abstract

Suppression of activation or proliferation, or induction of apoptosis in hepatic stellate cells (HSCs) have been proposed as therapeutic strategies against liver fibrosis. Salvia miltiorrhiza has been reported to exert antifibrotic effects in rats with hepatic fibrosis, but its mechanisms of action remain to be clarified. We have investigated the effects of salvianolic acid A (Sal A), an active principle from S. miltiorrhiza, on the proliferation-related biomarkers in a cell line of rat HSCs (HSC-T6) stimulated with platelet-derived growth factor-BB homodimer (PDGF-BB). DNA synthesis (bromodeoxyuridine (BrdU) incorporation), cell cycle related proteins and apoptosis markers were determined to evaluate the inhibitory effects of Sal A. The results showed that Sal A (1-10 M) concentration-dependently attenuated PDGF-BB-stimulated proliferation (BrdU incorporation) in HSC-T6 cells. Sal A at 10 M induced cell apoptosis in PDGF-BB-incubated HSCs, together with a reduction of Bcl-2 protein expression, induction of cell cycle inhibitory proteins p21 and p27, and down-regulation of cyclins D1 and E, suppression of Akt phosphorylation, reduction in PDGF receptor phosphorylation, and an increase in caspase-3 activity. Sal A exerted no direct cytotoxicity on primary hepatocytes and HSC-T6 cells under experimental concentrations. Our results suggested that Sal A inhibited PDGF-BB-activated HSC proliferation, partially through apoptosis induction.

NeuroAiD® (MLC601) and Amyloid Precursor Protein Processing

“…3). So far, 13 of the components found within MLC601 have been found to have the ability to reverse and prevent events associated with Aβ-induced toxicity [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45]. Specifically, radix salviae miltiorrhizae, radix paeoniae rubrae, radix angelicae sinensis, radix astragali, rhizoma chuanxiong and Carthamus tinctorius have all been shown to ameliorate critical toxic events within the amyloid cascade hypothesis (fig.…”

Effects of upregulated expression of microRNA-16 on biological properties of culture-activated hepatic stellate cells

“…Following liver injury of any etiology, HSCs undergo a response known as ''activation,'' which is the transition of quiescent cells into proliferative, fibrogenic, and contractile myofibroblasts [2]. Several studies recently reported that the number of HSCs are increased associated with its biological properties of HSCs proliferation and counteration of apoptosis, when stimulated by fibrogenic stimuli [3][4][5]. However, limited understanding of the gene regulation made these characteristics of HSCs still vague and controversial until now.…”

A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometry

“…However, the pharmacological research on SAA has lagged behind relative to SAB because of the difficulty in obtaining a large amount of pure compound due to the very low content in Danshen and the inability to synthesize SAA chemically. After the synthesis was resolved (Zhuang et al, 1996;Zhang et al, 2007), SAA attracted a great deal of attention for its beneficial effects as demonstrated by studies in animal and cell line models, such as protection against liver experimental injury and fibrosis (Hu et al, 2000;Liu et al, 2000aLiu et al, ,b, 2001Lin et al, 2006;Wu et al, 2007), protective effect against experimental impairment of memory (Du and Zhang, 1997) and protection against adriamycin toxicity of the rat heart (Lin et al, 1992). More recently, SAA was found to have some unique pharmacological actions from SAB, including reducing the blood level of glucose, glycosylated hemoglobin, and advanced glycation endproducts (AGEs), improving glucose metabolism disorders, and ameliorating oxidative stress of diabetic rats in our laboratory.…”