Tags

Type your tag names separated by a space and hit enter

Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways.
Liver Int. 2015 Apr; 35(4):1222-33.LI

Abstract

BACKGROUND & AIMS

Luteolin has been reported to exert antifibrogenic effects in CCl4 -induced hepatic fibrosis in mice. However, limited information is available on the cellular and molecular events responsible for this effect. This study focused on the action of luteolin on hepatic stellate cells (HSCs) and the relevant signalling molecules and pathways as well as the antifibrotic efficacy in multiple models of fibrosis.

METHODS

The in vitro effect of luteolin on rat HSCs and HSC-T6 cells was assessed using proliferation assays, invasion chamber, quantitative real-time PCR analysis and Western blotting. The in vivo effect of luteolin on progression of fibrosis was assessed in three experimental rat models induced by CCl4 , dimethylnitrosamine (DMN) and bile duct ligation (BDL).

RESULTS

Luteolin inhibited proliferation, migration, collagen synthesis as well as expression of fibrosis-related genes in the activated HSCs and HSC-T6 cells stimulated with or without transforming growth factor-β1(TGFβ1) or platelet-derived growth factor (PDGF). Luteolin induced HSC apoptosis associated with the increased caspase 3 activity and p53 expression, and induced G1 arrest with the decreased expression of bcl-2, Cyclin E and p-Cdk-2. Moreover, luteolin significantly inhibited PDGF and TGFβ1-simulated phosphorylation of AKT and Smad pathway. In vivo study showed that luteolin administration markedly alleviated hepatic fibrosis along with reduced elevations of alanine aminotransferase and aspartate aminotransferase. HSCs were found to undergo apoptosis and decreased expression of p-Smad2 and p-AKT in luteolin-treated animals.

CONCLUSIONS

This study demonstrates that luteolin prevents the progression of liver fibrosis through multiple mechanisms and indicates that luteolin has potential for effective treatment of liver fibrosis.

Authors+Show Affiliations

Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25040634

Citation

Li, Jie, et al. "Antifibrotic Effects of Luteolin On Hepatic Stellate Cells and Liver Fibrosis By Targeting AKT/mTOR/p70S6K and TGFβ/Smad Signalling Pathways." Liver International : Official Journal of the International Association for the Study of the Liver, vol. 35, no. 4, 2015, pp. 1222-33.
Li J, Li X, Xu W, et al. Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways. Liver Int. 2015;35(4):1222-33.
Li, J., Li, X., Xu, W., Wang, S., Hu, Z., Zhang, Q., Deng, X., Wang, J., Zhang, J., & Guo, C. (2015). Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways. Liver International : Official Journal of the International Association for the Study of the Liver, 35(4), 1222-33. https://doi.org/10.1111/liv.12638
Li J, et al. Antifibrotic Effects of Luteolin On Hepatic Stellate Cells and Liver Fibrosis By Targeting AKT/mTOR/p70S6K and TGFβ/Smad Signalling Pathways. Liver Int. 2015;35(4):1222-33. PubMed PMID: 25040634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antifibrotic effects of luteolin on hepatic stellate cells and liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways. AU - Li,Jie, AU - Li,Xingxia, AU - Xu,Weiheng, AU - Wang,Shaozhan, AU - Hu,Zhenlin, AU - Zhang,Qing, AU - Deng,Xing, AU - Wang,Jing, AU - Zhang,Junping, AU - Guo,Cheng, Y1 - 2014/08/05/ PY - 2013/11/05/received PY - 2014/07/06/accepted PY - 2014/7/22/entrez PY - 2014/7/22/pubmed PY - 2015/12/17/medline KW - AKT KW - Smad KW - activation KW - hepatic fibrosis KW - hepatic stellate cells KW - luteolin SP - 1222 EP - 33 JF - Liver international : official journal of the International Association for the Study of the Liver JO - Liver Int. VL - 35 IS - 4 N2 - BACKGROUND & AIMS: Luteolin has been reported to exert antifibrogenic effects in CCl4 -induced hepatic fibrosis in mice. However, limited information is available on the cellular and molecular events responsible for this effect. This study focused on the action of luteolin on hepatic stellate cells (HSCs) and the relevant signalling molecules and pathways as well as the antifibrotic efficacy in multiple models of fibrosis. METHODS: The in vitro effect of luteolin on rat HSCs and HSC-T6 cells was assessed using proliferation assays, invasion chamber, quantitative real-time PCR analysis and Western blotting. The in vivo effect of luteolin on progression of fibrosis was assessed in three experimental rat models induced by CCl4 , dimethylnitrosamine (DMN) and bile duct ligation (BDL). RESULTS: Luteolin inhibited proliferation, migration, collagen synthesis as well as expression of fibrosis-related genes in the activated HSCs and HSC-T6 cells stimulated with or without transforming growth factor-β1(TGFβ1) or platelet-derived growth factor (PDGF). Luteolin induced HSC apoptosis associated with the increased caspase 3 activity and p53 expression, and induced G1 arrest with the decreased expression of bcl-2, Cyclin E and p-Cdk-2. Moreover, luteolin significantly inhibited PDGF and TGFβ1-simulated phosphorylation of AKT and Smad pathway. In vivo study showed that luteolin administration markedly alleviated hepatic fibrosis along with reduced elevations of alanine aminotransferase and aspartate aminotransferase. HSCs were found to undergo apoptosis and decreased expression of p-Smad2 and p-AKT in luteolin-treated animals. CONCLUSIONS: This study demonstrates that luteolin prevents the progression of liver fibrosis through multiple mechanisms and indicates that luteolin has potential for effective treatment of liver fibrosis. SN - 1478-3231 UR - https://www.unboundmedicine.com/medline/citation/25040634/Antifibrotic_effects_of_luteolin_on_hepatic_stellate_cells_and_liver_fibrosis_by_targeting_AKT/mTOR/p70S6K_and_TGFβ/Smad_signalling_pathways_ L2 - https://doi.org/10.1111/liv.12638 DB - PRIME DP - Unbound Medicine ER -