Mogroside IVE attenuates experimental liver fibrosis in mice and inhibits HSC activation through downregulating TLR4-mediated pathways

Fengyan Cao, Yunfang Zhang, Weiguang Li, Kuniyoshi Shimizu, Haifeng Xie, Chaofeng Zhang

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Liver fibrosis has been emphasized as a serious threat to human health. There is currently no effective clinical drug treatment. Although mogrosides (MGs) have extensive pharmacological effects with minimal toxicity, their effects on liver function, inflammation, matrix metalloproteinases and hepatic stellate cell (HSC) activation remain to be researched. In the current study, we investigated whether mogroside IVE (MGIVE), a main compound isolated from MGs, provided protection against liver fibrosis in mice. MGIVE (25 mg/kg) significantly reduced carbon tetrachloride (CCl 4 )-induced inflammatory infiltration, pro-inflammatory cytokine release, and myeloperioxide (MPO) activity, as well as improved liver function in CCl 4 -treated mice. Additionally, MGIVE also significantly impaired CCl 4 -induced increases in liver fibrotic marker expression, such as collagen type I and hypoxia inducible factor-1α (HIF-1α). Further investigation indicated that the possible molecular target of MGIVE is the toll-like receptor 4 (TLR4)-mediated pathway, and MGIVE treatment significantly prevented CCl 4 -induced transforming growth factor-β1 (TGF-β1) overexpression and the phosphorylation of mitogen activated protein kinase (MAPK) in vivo. In vitro tests of HSCs or RAW 264.7 cells challenged with TGF-β1 or lipopolysaccharide (LPS) demonstrated that TLR4 expression partly mediated the anti-fibrotic effects of MGIVE. In conclusion, supplementation with MGIVE may attenuate liver fibrosis through inhibiting the TLR4 signaling pathway, including MyD88 and MAPKs, as well as HIF-1α. MGIVE may act as a therapeutic potential drug for the treatment of liver fibrosis via the TLR4/HIF-1α cohort signaling pathway.

元の言語英語
ページ(範囲)183-192
ページ数10
ジャーナルInternational Immunopharmacology
55
DOI
出版物ステータス出版済み - 2 1 2018

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Hepatic Stellate Cells
Toll-Like Receptor 4
Hypoxia-Inducible Factor 1
Liver Cirrhosis
Down-Regulation
Transforming Growth Factors
Liver
Carbon Tetrachloride
Collagen Type I
Mitogen-Activated Protein Kinases
Matrix Metalloproteinases
Pharmaceutical Preparations
Lipopolysaccharides
Phosphorylation
Pharmacology
Cytokines
Inflammation
Health
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

これを引用

Mogroside IVE attenuates experimental liver fibrosis in mice and inhibits HSC activation through downregulating TLR4-mediated pathways. / Cao, Fengyan; Zhang, Yunfang; Li, Weiguang; Shimizu, Kuniyoshi; Xie, Haifeng; Zhang, Chaofeng.

:: International Immunopharmacology, 巻 55, 01.02.2018, p. 183-192.

研究成果: ジャーナルへの寄稿記事

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abstract = "Liver fibrosis has been emphasized as a serious threat to human health. There is currently no effective clinical drug treatment. Although mogrosides (MGs) have extensive pharmacological effects with minimal toxicity, their effects on liver function, inflammation, matrix metalloproteinases and hepatic stellate cell (HSC) activation remain to be researched. In the current study, we investigated whether mogroside IVE (MGIVE), a main compound isolated from MGs, provided protection against liver fibrosis in mice. MGIVE (25 mg/kg) significantly reduced carbon tetrachloride (CCl 4 )-induced inflammatory infiltration, pro-inflammatory cytokine release, and myeloperioxide (MPO) activity, as well as improved liver function in CCl 4 -treated mice. Additionally, MGIVE also significantly impaired CCl 4 -induced increases in liver fibrotic marker expression, such as collagen type I and hypoxia inducible factor-1α (HIF-1α). Further investigation indicated that the possible molecular target of MGIVE is the toll-like receptor 4 (TLR4)-mediated pathway, and MGIVE treatment significantly prevented CCl 4 -induced transforming growth factor-β1 (TGF-β1) overexpression and the phosphorylation of mitogen activated protein kinase (MAPK) in vivo. In vitro tests of HSCs or RAW 264.7 cells challenged with TGF-β1 or lipopolysaccharide (LPS) demonstrated that TLR4 expression partly mediated the anti-fibrotic effects of MGIVE. In conclusion, supplementation with MGIVE may attenuate liver fibrosis through inhibiting the TLR4 signaling pathway, including MyD88 and MAPKs, as well as HIF-1α. MGIVE may act as a therapeutic potential drug for the treatment of liver fibrosis via the TLR4/HIF-1α cohort signaling pathway.",
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AU - Zhang, Chaofeng

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AB - Liver fibrosis has been emphasized as a serious threat to human health. There is currently no effective clinical drug treatment. Although mogrosides (MGs) have extensive pharmacological effects with minimal toxicity, their effects on liver function, inflammation, matrix metalloproteinases and hepatic stellate cell (HSC) activation remain to be researched. In the current study, we investigated whether mogroside IVE (MGIVE), a main compound isolated from MGs, provided protection against liver fibrosis in mice. MGIVE (25 mg/kg) significantly reduced carbon tetrachloride (CCl 4 )-induced inflammatory infiltration, pro-inflammatory cytokine release, and myeloperioxide (MPO) activity, as well as improved liver function in CCl 4 -treated mice. Additionally, MGIVE also significantly impaired CCl 4 -induced increases in liver fibrotic marker expression, such as collagen type I and hypoxia inducible factor-1α (HIF-1α). Further investigation indicated that the possible molecular target of MGIVE is the toll-like receptor 4 (TLR4)-mediated pathway, and MGIVE treatment significantly prevented CCl 4 -induced transforming growth factor-β1 (TGF-β1) overexpression and the phosphorylation of mitogen activated protein kinase (MAPK) in vivo. In vitro tests of HSCs or RAW 264.7 cells challenged with TGF-β1 or lipopolysaccharide (LPS) demonstrated that TLR4 expression partly mediated the anti-fibrotic effects of MGIVE. In conclusion, supplementation with MGIVE may attenuate liver fibrosis through inhibiting the TLR4 signaling pathway, including MyD88 and MAPKs, as well as HIF-1α. MGIVE may act as a therapeutic potential drug for the treatment of liver fibrosis via the TLR4/HIF-1α cohort signaling pathway.

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