AI Article Synopsis
- Chronic liver injury leads to fibrosis and cirrhosis through extracellular matrix component synthesis, with TGF-β1 playing a significant role in this process.
- Phyllanthin, a compound from the plant Phyllanthus amarus, was studied for its ability to inhibit the ALK5 receptor, crucial in the progression of liver fibrosis.
- The study demonstrated that phyllanthin can protect the liver by down-regulating the TGF signaling pathway, significantly reducing fibrosis indicators linked to chronic liver injury.
Article Abstract
Chronic injury to liver triggers synthesis of extracellular matrix components resulting in progressive fibrosis and eventually cirrhosis. Transforming growth factor-β1 (TGF-β1) transduces its signal by binding to TGF-β type 1 receptor kinase or activin like kinase (ALK5) receptor and mediates hepatic fibrosis by increasing the transcription of downstream entities such as collagen via Smad2 and Smad3. The present study was carried out to investigate the mechanism by which phyllanthin, a hepatoprotective lignin isolated from the plant Phyllanthus amarus (P. amarus) exerts its anti-fibrotic effect. The inhibitory role of phyllanthin on ALK5 was first analyzed using molecular docking experiments. Phyllanthin was found to effectively bind to serine (Ser) 280 at the active site of ALK5 by forming hydrogen bonds. The in vivo protective effect of phyllanthin against carbon tetrachloride (CCl4)-induced hepatic fibrosis was established by studying the protein expressions of TGF-β1, ALK5 and Smad2 and 3 and by determining various biochemical and histopathological parameters. Phyllanthin was found to exert its anti-fibrotic effect by down-regulating TGF signaling pathway via ALK5 and Smad2 and 3 inhibition.
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| http://dx.doi.org/10.3109/15376516.2015.1077361 | DOI Listing |
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