Piperlongumine attenuates bile duct ligation-induced liver fibrosis in mice via inhibition of TGF-β1/Smad and EMT pathways
| Autor: | Mohd Aslam Saifi, Shrilekha Chilvery, Sapana Bansod, Chandraiah Godugu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Liver Cirrhosis
Male 0301 basic medicine Epithelial-Mesenchymal Transition Immunology Smad Proteins SMAD Protective Agents Extracellular matrix Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Hepatic Stellate Cells medicine Animals Immunology and Allergy Epithelial–mesenchymal transition Ligation Piperlongumine Pharmacology Liver injury Dioxolanes medicine.disease 030104 developmental biology Liver chemistry 030220 oncology & carcinogenesis Cancer research Hepatic stellate cell Cytokines Bile Ducts Collagen Signal Transduction Transforming growth factor |
| Zdroj: | International Immunopharmacology. 88:106909 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2020.106909 |
| Popis: | Liver fibrosis (LF) is a progressive liver injury that may result in excessive accumulation of extracellular matrix (ECM). However, transforming growth factor-beta (TGF-β) and epithelial to mesenchymal transition (EMT) play a central role in the progression of LF through the activation of matrix producing hepatic stellate cells (HSCs). Piperlongumine (PL), an alkaloid extracted from Piper longum, has been reported to possess anti-inflammatory and antioxidant activities in various diseases but its hepatoprotective and antifibrotic effects have not been reported yet. Therefore, in the present study, we investigated the protective effect of PL in bile duct ligation (BDL)-induced LF model and explored the molecular mechanisms underlying its antifibrotic effect. BDL group displayed a significant degree of liver damage, oxidative-nitrosative stress, hepatic inflammation and collagen deposition in the liver while these pathological changes were effectively attenuated by treatment with PL. Furthermore, we found that PL treatment greatly inhibited HSCs activation and ECM deposition via downregulation of fibronectin, α-SMA, collagen1a, and collagen3a expression in the fibrotic livers. We further demonstrated that PL administration significantly inhibited TGF-β1/Smad and EMT signaling pathways. Our study demonstrated that PL exerted strong hepatoprotective and antifibrotic activities against BDL-induced LF and might be an effective therapeutic agent for the treatment of LF. |
| Databáze: | OpenAIRE |
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