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Potent effects of dioscin against liver fibrosis.

Zhang X, Han X, Yin L, Xu L, Qi Y, Xu Y, Sun H, Lin Y, Liu K, Peng J - Sci Rep (2015)

Bottom Line: Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes.Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-γ (PPAR-γ) expression and significantly reduced a-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen α1 (I) (COL1A1) and collagen α1 (III) (COL3A1) levels in vitro.Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-β1/Smad, Wnt/β-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.

ABSTRACT
We previously reported the promising effects of dioscin against liver injury, but its effect on liver fibrosis remains unknown. The present work investigated the activities of dioscin against liver fibrosis and the underlying molecular mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-γ (PPAR-γ) expression and significantly reduced a-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen α1 (I) (COL1A1) and collagen α1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs activation and induced apoptosis in activated HSCs. In vivo, dioscin significantly improved body weight and hydroxylproline, laminin, α-SMA, TGF-β1, COL1A1 and COL3A1 levels, which were confirmed by histopathological assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-β1/Smad, Wnt/β-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs. In conclusion, dioscin exhibited potent effects against liver fibrosis through the modulation of multiple targets and signaling pathways and should be developed as a novel candidate for the treatment of liver fibrosis in the future.

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Inhibitory effects of dioscin on CCl4-induced hepatotoxicity.In program I, the rats were injected twice a week with CCl4 during 7 weeks in the presence or absence of dioscin, and in program II, CCl4 was injected for 10 weeks without dioscin, or after 4 weeks of CCl4, dioscin was administered together with CCl4 for additional times. (A–B) Effects of dioscin on rat body weights and livers. (C) Effects of dioscin on serum AST and ALT activities in rats as a measure for liver injury. (D) Effects of dioscin on GSH, GSH-Px, SOD and MDA levels. (E) H&E staining of representative liver sections (magnification, 100×). Values are expressed as the mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.
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f3: Inhibitory effects of dioscin on CCl4-induced hepatotoxicity.In program I, the rats were injected twice a week with CCl4 during 7 weeks in the presence or absence of dioscin, and in program II, CCl4 was injected for 10 weeks without dioscin, or after 4 weeks of CCl4, dioscin was administered together with CCl4 for additional times. (A–B) Effects of dioscin on rat body weights and livers. (C) Effects of dioscin on serum AST and ALT activities in rats as a measure for liver injury. (D) Effects of dioscin on GSH, GSH-Px, SOD and MDA levels. (E) H&E staining of representative liver sections (magnification, 100×). Values are expressed as the mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.

Mentions: Hepatic fibrosis in rats was produced by intraperitoneal (i.p.) injection of CCl4 for 7 or 10 weeks. Dioscin mixed with 0.5% carboxymethylcellulose (CMC-Na) was administered intragastrica- lly (i.g.) at the doses of 20, 40 and 60 14mg/kg once daily. Our in vivo tests showed that the body weights of rats in model groups were lower than those of in control groups (Figure 3A). However, dioscin significantly prevented the decrease in body weights relative to model groups. As shown in Figure 3B, the livers from CCl4-treated rats were puffy and stiff, and acquired an irregular and granular surface, which were all ameliorated by dioscin. In addition, the relative liver weight (%) was also reduced in dioscin-treated rats. The serum AST and ALT activities in CCl4-treated rats were markedly increased, which were also significantly suppressed by the compound (Figure 3C).


Potent effects of dioscin against liver fibrosis.

Zhang X, Han X, Yin L, Xu L, Qi Y, Xu Y, Sun H, Lin Y, Liu K, Peng J - Sci Rep (2015)

Inhibitory effects of dioscin on CCl4-induced hepatotoxicity.In program I, the rats were injected twice a week with CCl4 during 7 weeks in the presence or absence of dioscin, and in program II, CCl4 was injected for 10 weeks without dioscin, or after 4 weeks of CCl4, dioscin was administered together with CCl4 for additional times. (A–B) Effects of dioscin on rat body weights and livers. (C) Effects of dioscin on serum AST and ALT activities in rats as a measure for liver injury. (D) Effects of dioscin on GSH, GSH-Px, SOD and MDA levels. (E) H&E staining of representative liver sections (magnification, 100×). Values are expressed as the mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389718&req=5

f3: Inhibitory effects of dioscin on CCl4-induced hepatotoxicity.In program I, the rats were injected twice a week with CCl4 during 7 weeks in the presence or absence of dioscin, and in program II, CCl4 was injected for 10 weeks without dioscin, or after 4 weeks of CCl4, dioscin was administered together with CCl4 for additional times. (A–B) Effects of dioscin on rat body weights and livers. (C) Effects of dioscin on serum AST and ALT activities in rats as a measure for liver injury. (D) Effects of dioscin on GSH, GSH-Px, SOD and MDA levels. (E) H&E staining of representative liver sections (magnification, 100×). Values are expressed as the mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.
Mentions: Hepatic fibrosis in rats was produced by intraperitoneal (i.p.) injection of CCl4 for 7 or 10 weeks. Dioscin mixed with 0.5% carboxymethylcellulose (CMC-Na) was administered intragastrica- lly (i.g.) at the doses of 20, 40 and 60 14mg/kg once daily. Our in vivo tests showed that the body weights of rats in model groups were lower than those of in control groups (Figure 3A). However, dioscin significantly prevented the decrease in body weights relative to model groups. As shown in Figure 3B, the livers from CCl4-treated rats were puffy and stiff, and acquired an irregular and granular surface, which were all ameliorated by dioscin. In addition, the relative liver weight (%) was also reduced in dioscin-treated rats. The serum AST and ALT activities in CCl4-treated rats were markedly increased, which were also significantly suppressed by the compound (Figure 3C).

Bottom Line: Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes.Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-γ (PPAR-γ) expression and significantly reduced a-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen α1 (I) (COL1A1) and collagen α1 (III) (COL3A1) levels in vitro.Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-β1/Smad, Wnt/β-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.

ABSTRACT
We previously reported the promising effects of dioscin against liver injury, but its effect on liver fibrosis remains unknown. The present work investigated the activities of dioscin against liver fibrosis and the underlying molecular mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-γ (PPAR-γ) expression and significantly reduced a-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen α1 (I) (COL1A1) and collagen α1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs activation and induced apoptosis in activated HSCs. In vivo, dioscin significantly improved body weight and hydroxylproline, laminin, α-SMA, TGF-β1, COL1A1 and COL3A1 levels, which were confirmed by histopathological assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-β1/Smad, Wnt/β-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs. In conclusion, dioscin exhibited potent effects against liver fibrosis through the modulation of multiple targets and signaling pathways and should be developed as a novel candidate for the treatment of liver fibrosis in the future.

Show MeSH
Related in: MedlinePlus