Effects of β-sitosterol derived from Artemisia capillaris on the activated human hepatic stellate cells and dimethylnitrosamine-induced mouse liver fibrosis

Abstract

Backgroundβ-sitosterol is a cholesterol-like phytosterol, which widely distributed in the plant kingdom. Here, anti-fibrotic effect of the β-sitosterol was studied using the activated human hepatic stellate cell (HSC) model and dimethylnitrosamine (DMN)-induced mouse hepatic fibrosis model.MethodHSCs were activated by transforming growth factor-β (TGF-β) and the collagen-1 and α-smooth muscle actin (α-SMA) expressions were measured at the mRNA and protein level. We also studied the effect β-sitosterol using DMN-induced mouse hepatic fibrosis model. We then measured the collagen-1 and α-SMA expression levels in vivo to investigate anti-hepatofibrotic effect of β-sitosterol, at both of the mRNA and protein level.Resultsβ-sitosterol down regulated the mRNA and protein expression levels of collagen-1 and α-SMA in activated HSC. Oral administration of the β-sitosterol successfully alleviated the DMN-induced mouse liver damage and prevented collagen accumulation. The mRNA and protein expression levels of collagen-1 and α-SMA were also down regulated in β-sitosterol treated mouse group.ConclusionsThis study shows the effect of β-sitosterol on the TGF-β -or DMN-induced hepatofibrosis. Hence, we demonstrate the β-sitosterol as a potential therapeutic agent for the hepatofibrosis.

A Survey of Therapeutic Effects ofArtemisia capillarisin Liver Diseases

“…Liver fibrosis is a healing process that occurs in damaged liver tissues and can progress to liver cirrhosis or carcinoma [ 7 , 44 , 45 ]. The accumulation of fibrotic factors like collagen-1 and α -smooth muscle actin ( α -SMA) in the liver is attributable to hepatic stellate cells induced by the tumor growth factor- (TGF-) β or platelet-derived growth factor (PDGF) [ 46 ].…”

“…However, the statistical significance was not proven, and Artemisia iwayomogi rather than A. capillaris was more effective against the fibrotic changes [ 3 ]. The β -sitosterol derived from A. capillaris administered at 120 μ M and 40 mg/kg significantly regulated Col1A1 and α -SMA in LX2 cells and dimethylnitrosamine- (DMN-) induced fibrotic mice [ 7 ]. This effect was mediated by activating caspase-3, caspase-9, and Bcl-2-associated X protein (BAX) and inhibiting B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia- (Mcl-) 1, phosphorylation of mitogen-activated protein kinase (MEK), and extracellular signal-regulated kinases (ERK) [ 7 ].…”

Effect of Yi Guan Jian decoction on differentiation of bone marrow mesenchymalstem cells into hepatocyte-like cells in dimethylnitrosamine-induced liver cirrhosis in mice

“…It is widely used in experimental animals, including mice, to create a low-mortality and reproducible model of liver cirrhosis (8,9). DMN significantly induces the deposition of collagen fibers and the formation of fibrous septa, as reported by previous studies (10,11), and as demonstrated by MT staining in the present study.…”

A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats

“…Liver fibrosis frequently resulted from liver chronic damage can lead to development of liver cirrhosis and consequent failure of hepatic function. During the process of fibrogenesis, the proliferation and activation of HSCs are believed to play essential roles [ 24 , 25 ]. Therefore, suppression or reversal of HSC activation is considered as the main target of hepatic fibrosis.…”