Andrographolide Ameliorates Liver Fibrosis in Mice: Involvement of TLR4/NF-κB and TGF-β1/Smad2 Signaling Pathways.
Liteng LinRui LiMingyue CaiJingjun HuangWensou HuangYongjian GuoLiuhong YangGuizhi YangTian LanKang-Shun ZhuPublished in: Oxidative medicine and cellular longevity (2018)
Liver fibrosis is characterized by activated hepatic stellate cells (HSC) and extracellular matrix accumulation. Blocking the activation of HSC and the inflammation response are two major effective therapeutic strategies for liver fibrosis. In addition to the long history of using andrographolide (Andro) for inflammatory disorders, we aimed at elucidating the pharmacological effects and potential mechanism of Andro on liver fibrosis. In this study, liver fibrosis was induced by carbon tetrachloride (CCl4) and the mice were intraperitoneally injected with Andro for 6 weeks. HSC cell line (LX-2) and primary HSC were also treated with Andro in vitro. Treatment of CCl4-induced mice with Andro decreased the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), Sirius red staining as well as the expression of α smooth muscle actin (α-SMA) and transforming growth factor- (TGF-) β1. Furthermore, the expression of Toll-like receptor (TLR)4 and NF-κB p50 was also inhibited by Andro. Additionally, in vitro data confirmed that Andro treatment not only attenuated the expression of profibrotic and proinflammatory factors but also blocked the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways. These results demonstrate that Andro prevents liver inflammation and fibrosis, which is in correlation with the inhibition of the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways, highlighting Andro as a potential therapeutic strategy for liver fibrosis.
Keyphrases
- liver fibrosis
- transforming growth factor
- toll like receptor
- nuclear factor
- epithelial mesenchymal transition
- signaling pathway
- inflammatory response
- lps induced
- oxidative stress
- induced apoptosis
- poor prognosis
- immune response
- pi k akt
- extracellular matrix
- smooth muscle
- high fat diet induced
- diabetic rats
- binding protein
- combination therapy
- mouse model
- deep learning
- type diabetes
- risk assessment
- replacement therapy
- climate change
- adipose tissue
- endothelial cells
- endoplasmic reticulum stress