| Autor: |
Seo, Jae Hwa, Lee, Hyo‐Jung, Sim, Deok Yong, Park, Ji Eon, Ahn, Chi‐Hoon, Park, Su‐Yeon, Cho, Ah‐Reum, Koo, Jinsuk, Shim, Bum Sang, Kim, Bonglee, Kim, Sung‐Hoon |
| Zdroj: |
Phytotherapy Research; Sep2023, Vol. 37 Issue 9, p4092-4101, 10p |
| Abstrakt: |
Though Honokiol was known to have anti‐inflammatory, antioxidant, anticancer, antithrombotic, anti‐viral, metabolic, antithrombotic, and neurotrophic activities, the underlying mechanisms of Honokiol on epithelial–mesenchymal transition (EMT) mediated liver fibrosis still remain elusive so far. Anti‐EMT and antifibrotic effects of Honokiol were explored in murine AML‐12 hepatocyte cells by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay, wound healing assay, Western blotting and also in CCl4‐induced liver injury mouse model by immunohistochemistry. Honokiol significantly suppressed transforming growth factor β1 (TGF‐β1)‐induced EMT and migration of AML‐12 cells along with decreased EMT phenotypes such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in TGF‐β1‐treated AML‐12 cells. Consistently, Honokiol suppressed the expression of Snail and transmembrane protease serine 4 (TMPRSS4), but not p‐Smad3, and activated E‐cadherin in TGF‐β1‐treated AML‐12 cells. Additionally, Honokiol reduced the expression of β‐catenin, p‐AKT, p‐ERK, p‐p38 and increased phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and JNK in TGF‐β1‐treated AML‐12 cells via TGF‐β1/nonSmad pathway. Conversely, GSK3β inhibitor SB216763 reversed the ability of Honokiol to reduce Snail, β‐catenin and migration and activate E‐cadherin in TGF‐β1‐treated AML‐12 cells. Also, Honokiol suppressed hepatic steatosis and necrosis by reducing the expression of TGF‐β1 and α‐SMA in liver tissues of CCl4 treated mice. These findings provide scientific evidence that Honokiol suppresses EMT and hepatic fibrosis via activation of E‐cadherin/GSK3β/JNK and inhibition of AKT/ERK/p38/β‐catenin/TMPRSS4 signaling axis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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