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. 2014 Sep 27:14:363.
doi: 10.1186/1472-6882-14-363.

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

Ki-Suk Kim, Hea Jung Yang, Jae-Youl Lee, Yun-Cheol Na, Soo-Young Kwon, Young-Chul Kim, Jang-Hoon Lee  1 , Hyeung-Jin Jang
Affiliations

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

Ki-Suk Kim et al. BMC Complement Altern Med. .

Abstract

Background: β-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.

Method: HSCs 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.

Results: β-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.

Conclusions: This 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.

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Figures

Figure 1
Figure 1
GC/MS. Selected ion chromatograms of β-sitosterol standard (A) and Artemisia capillaris water extract (B) diluted in methanol.
Figure 2
Figure 2
Effects of TGF-β treatment on the activation of HSCs. Relatively expressed MMP1 (A), MMP2 (B), COL1A1 (C), ACTA2 (D), and GFAP (E) mRNA levels were measured by real-time quantitative PCR. Experiments were carried out at least twice performed in triplicate. Statistical significance determined by one-way ANOVA; values are means ± SEM; *, p < 0.05; ***, p < 0.001 vs control group.
Figure 3
Figure 3
Effects of β -sitosterol on the collagen-1 and α-SMA mRNA expressions in activated HSCs. Relatively expressed COL1A1 (A) and ACTA2 (B) levels were measured by real-time quantitative PCR. Experiments were carried out at least twice performed in triplicate. Statistical significance determined by one-way ANOVA; values are means ± SEM; ***, p < 0.001 vs TGF-β-treated group. ###, p < 0.001 vs control group.
Figure 4
Figure 4
Cell viability assay of β -sitosterol. Statistical significance determined by one-way ANOVA; values are means ± SEM.
Figure 5
Figure 5
Effects of β -sitosterol on collagen-1 and α -SMA protein expression in activated HSCs. (A) The western blot results representative three separate experiments. (B) Each protein expressions which normalized by β-actin expression, was measured by densitometry analysis. Statistical significance determined by one-way ANOVA; values are means ± SEM; *, p < 0.05; ***, p < 0.001 vs TGF-β-treated group.
Figure 6
Figure 6
Effects of β -sitosterol on DMN-induced mouse liver fibrosis. (A) H&E staining demonstrates the amount of damaged liver tissue. (B) The amount of collagen accumulation was determined by IHC.
Figure 7
Figure 7
Effects of β -sitosterol on collagen-1 and α -SMA mRNA expression in DMN-induced mouse liver fibrosis. Relatively expressed Col1a1 (A) and Acta2 (B) levels were measured by real-time quantitative PCR. Experiments were carried out in triplicate. Statistical significance determined by one-way ANOVA; values are means ± SEM; ***, p < 0.001 vs TGF-β-treated group. ###, p < 0.001 vs control group.
Figure 8
Figure 8
Effects of β -sitosterol on collagen-1 and α -SMA protein expression in DMN-induced mouse liver fibrosis. (A) The western blot results representative three separate experiments. (B-C) Statistical significance determined by one-way ANOVA; values are means ± SEM; ***, p < 0.001 vs TGF-β-treated group. ###, p < 0.001 vs control group.
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Pre-publication history
    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6882/14/363/prepub

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