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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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Dioscin attenuated liver fibrosis in vivo.(A–B) Effects of dioscin on liver fibrosis by Masson and Sirius Red staining (magnification 100×). (C) Effects of dioscin on expression of α-SMA by immunostaining in liver tissues extracted from rats treated with CCl4 and dioscin for 7 weeks and 10 weeks (magnification 200×) (D) Effects of dioscin on hydroxyproline levels in rat livers. (E) Effects of dioscin on the mRNA levels of laminin, COL1A1 and COL3A1 in rats. The results are expressed as mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.
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f4: Dioscin attenuated liver fibrosis in vivo.(A–B) Effects of dioscin on liver fibrosis by Masson and Sirius Red staining (magnification 100×). (C) Effects of dioscin on expression of α-SMA by immunostaining in liver tissues extracted from rats treated with CCl4 and dioscin for 7 weeks and 10 weeks (magnification 200×) (D) Effects of dioscin on hydroxyproline levels in rat livers. (E) Effects of dioscin on the mRNA levels of laminin, COL1A1 and COL3A1 in rats. The results are expressed as mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.

Mentions: The livers from the control groups exhibited a normal lobular architecture, whereas samples from CCl4-treated groups exhibited severe hemorrhagic necrosis and inflammatory cell infiltration, which was dramatically attenuated by dioscin (Figure 3E). Dioscin also significantly decreased collagen fiber deposition based on Masson and Sirius Red staining (Figure 4A–B). Figure 4C demonstrates that the expression of α-SMA in dioscin-treated rats decreased significantly relative to CCl4-treated rats. These results were further confirmed by the levels of hepatic hydroxyproline (Figure 4D), laminin, Col1A1 and Col3A3 (Figure 4E) and by TEM assay (Supplemental Figure 6).


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)

Dioscin attenuated liver fibrosis in vivo.(A–B) Effects of dioscin on liver fibrosis by Masson and Sirius Red staining (magnification 100×). (C) Effects of dioscin on expression of α-SMA by immunostaining in liver tissues extracted from rats treated with CCl4 and dioscin for 7 weeks and 10 weeks (magnification 200×) (D) Effects of dioscin on hydroxyproline levels in rat livers. (E) Effects of dioscin on the mRNA levels of laminin, COL1A1 and COL3A1 in rats. The results are expressed as 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

f4: Dioscin attenuated liver fibrosis in vivo.(A–B) Effects of dioscin on liver fibrosis by Masson and Sirius Red staining (magnification 100×). (C) Effects of dioscin on expression of α-SMA by immunostaining in liver tissues extracted from rats treated with CCl4 and dioscin for 7 weeks and 10 weeks (magnification 200×) (D) Effects of dioscin on hydroxyproline levels in rat livers. (E) Effects of dioscin on the mRNA levels of laminin, COL1A1 and COL3A1 in rats. The results are expressed as mean ± SD (n ≥ 3). *p < 0.05, **p < 0.01 vs. model group; ##p < 0.01 vs. normal control group.
Mentions: The livers from the control groups exhibited a normal lobular architecture, whereas samples from CCl4-treated groups exhibited severe hemorrhagic necrosis and inflammatory cell infiltration, which was dramatically attenuated by dioscin (Figure 3E). Dioscin also significantly decreased collagen fiber deposition based on Masson and Sirius Red staining (Figure 4A–B). Figure 4C demonstrates that the expression of α-SMA in dioscin-treated rats decreased significantly relative to CCl4-treated rats. These results were further confirmed by the levels of hepatic hydroxyproline (Figure 4D), laminin, Col1A1 and Col3A3 (Figure 4E) and by TEM assay (Supplemental Figure 6).

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