In vitro protective effects of salvianolic acid B on primary hepatocytes and hepatic stellate cells

Lin, Yun‐Lian; Wu, Chia-Hung; Luo, Miao-Hua; Huang, Yeh-Jeng; Wang, Chuen-Neu; Shiao, Ming‐Shi; Huang, Yi-Tsau

doi:10.1016/j.jep.2005.10.021

Cited by 118 publications

(86 citation statements)

References 39 publications

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“…DMN is metabolized by hepatic cytochrome P4502E1 to more toxic products with reactive oxygen species (Jaeschke et al, 2002). Several groups including ours have observed that Salvia miltiorrhiza (S) and its active principle, salvianolic acid B, inhibited both CCl 4 -induced lipid peroxidation and TGF-β1-activated α-SMA secretion in rat HSCs (Zhao et al, 2004;Hsu et al, 2005;Lin et al, 2006b). Several in vivo studies also demonstrated that S treatment ameliorates hepatic fibrosis in rats (Wasser et al, 1998;Nan et al, 2001;Hsu et al, 2005).…”

Section: Discussionmentioning

confidence: 92%

Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats

Lin

Hsu²,

Chiu

et al. 2007

Phytotherapy Research

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Liver fibrosis has been characterized as chronic inflammatory processes involving multiple molecular pathogenetic pathways. This therapeutic study investigated whether a combination regimen of Salvia miltiorrhiza (S), Ligusticum chuanxiong (L) and Glycyrrhiza glabra (G) exerted in vivo antifibrotic effects on rats with hepatic fibrosis. Fibrosis was induced in rats by dimethylnitrosamine (DMN) administration for 4 weeks. Fibrotic rats were randomly assigned to one of the three groups: control, SLG (50 mg/kg) or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting 1 week after DMN injection. The results showed that fibrosis scores of livers from DMN-treated rats with SLG (1.13 ± ± ± ± ± 0.13) were significantly reduced in comparison with DMN-treated rats receiving vehicle (1.63 ± ± ± ± ± 0.18). Moreover, the hepatic collagen content of DMN rats was significantly reduced by either SLG or silymarin treatment. The double immunohistochemical staining results also showed that α α α α α-SMA positive cells with NFκ κ κ κ κB nuclear translocation were decreased in the fibrotic livers by SLG and silymarin treatments. The mRNA expression levels of TGF-β β β β β 1, α α α α α -SMA, collagen1α α α α α2, iNOS and ICAM-1 genes were attenuated by SLG and silymarin treatment. The results showed that SLG exerted antifibrotic effects in rats with DMN-induced hepatic fibrosis.

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Section: Discussionmentioning

confidence: 92%

Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats

Lin

Hsu²,

Chiu

et al. 2007

Phytotherapy Research

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“…Kim et al [21] revealed that Danshen water-soluble extract abrogated the LPS-induced NF-κB signaling pathway by targeting the I-κB-α kinase (IKK) complex in intestinal epithelial cells. Aqueous extract of Danshen was also found to reduce the oxidative stress in endothelial cell [22] and lipid peroxidation in hepatocytes and hepatic stellate cells [23] . DLA can effectively scavenge superoxide anion generated from the xanthin-xanthin oxidase system and protect the myocardial mitochondria from lipid peroxidation [24] .…”

Section: Compound Danshen Injection Improves Endotoxin-induced Microcmentioning

confidence: 99%

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

Han

Horie²,

Miura³

et al. 2007

WJG

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stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo , all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compoundDanshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance. INTRODUCTIONIt is now well-recognized that stimulation with lipopolysaccharide (LPS) leads to a number of responses in microcirculation, such as endothelial cell damage, an increase in rolling, adhesion and emigration of leukocytes in post-capillary venules, enhanced oxygenfree radical production, mast cell degranulation and protein efflux [1][2][3][4][5][6] . Furthermore, it is demonstrated that LPS stimulation evokes an increase in the expression of adhesion molecules, including L-selectin [7] and CD11b/CD18 in leukocytes, E-selectin and intercellular adhesion molecule 1 (ICAM-1) in endothelial cells [7][8][9][10][11][12][13] . In addition, LPS stimulation can cause the release of proinflammatory mediators and vasoactive substances, such Abstract AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS:LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITCalbumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro . RESULTS:The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule

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“…Bioassays of HSC-T6 activation had been established previously and reported by our group (Hsu et al 2005;Lin et al 2006a). HSC-T6 cells (1 Â 10 5 cells/mL/well) were cultured in Waymouth's medium (containing 10% foetal bovine serum (FBS), pH 7.0) in 24 wells at 37 C in 5% CO 2 .…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Antiproliferative effect of salvianolic acid A on rat hepatic stellate cells

Lin

Lee²,

Huang

et al. 2006

Journal of Pharmacy and Pharmacology

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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.

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In vitro protective effects of salvianolic acid B on primary hepatocytes and hepatic stellate cells

Cited by 118 publications

References 39 publications

Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats

Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery

Antiproliferative effect of salvianolic acid A on rat hepatic stellate cells

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