Effects of Isodon ternifolius extract on TLR 4/NF-κB/NLRP3 pathway in hepatic stellate cells and hepatocytes
- VernacularTitle:三叶香茶菜提取物对肝星状细胞和肝细胞TLR4/NF-κB/NLRP3通路的影响
- Author:
Le QIN
1
;
Yong CHEN
1
;
Guidong HUANG
1
;
Ruisheng WU
1
;
Daihua LIU
2
;
Zhipin ZHOU
2
Author Information
1. College of Pharmacy，Guangxi University of Chinese Medicine，Nanning 530200，China
2. Dept. of Pharmacy，Liuzhou People’s Hospital of Guangxi Medical University/Guangxi Key Laboratory of Clinical Disease Biotechnology，Guangxi Zhuang Autonomous Region Health Commission/Liuzhou Center for Gastrointestinal Chinese Patent Medicine Engineering Research，Guangxi Liuzhou 545006，China
- Publication Type:Journal Article
- Keywords:
Isodon ternifolius extract;
hepatic stellate cells;
hepatocytes;
TLR4/NF-κB/NLRP3 pathway;
hepatic fibrosis
- From:
China Pharmacy
2022;33(20):2448-2453
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of Isodon ternifolius extract on Toll -like receptor 4（TLR4）/nuclear factor - κB（NF-κB）/NOD-like receptor protein 3（NLRP3）pathway in hepatic stellate cells and hepatocytes . METHODS Using primary hepatic stellate cells and primary hepatocytes of rats as subjects ，inflammatory injury model was induced by lipopolysaccharide （LPS，100 ng/mL）. Using colchicine （1 μmol/L）as positive control and TLR 4 inhibitor（TAK-242，1 μmol/L）as reference ，the contents of transforming growth factor -β1（TGF-β1），α-smooth muscle actin （α-SMA），type Ⅰ collagen（COL-Ⅰ），COL-Ⅲ in the supernatant of hepatic stellate cells ，and the contents of alanine aminotransferase （ALT），aspartate aminotransferase （AST），interleukin-1β （IL-1β） and IL -18 in the supernatant of hepatocytes were detected after intervention with I. ternifolius extract（1 mg/mL）. The mRNA expressions of TLR 4，inhibitor α of NF -κB（IκBα），NF-κB p 65，NLRP3，Gasdermin D （GSDMD），apoptosis-associated speck -like protein containing CARD （ASC） and protein expressions of TLR 4， phosphorylated I κBα（p-IκBα），NF-κB p 65，NLRP3，GSDMD，ASC in the above cells were determined . RESULTS Compared with LPS model group ，the contents of TGF -β1，α-SMA， COL-Ⅰ and COL -Ⅲ in the supernatant of hepatic stellate cells and the contents of ALT ，AST，IL-1β and IL -18 in the supernatant of hepatocytes were significantly decreased ；the mRNA expressions of TLR 4，NF-κB p 65，NLRP3，GSDMD，ASC and the protein expressions of TLR 4，p-IκBα，NF-κB p 65，NLRP3，GSDMD，ASC in the two kinds of cells were significantly down - regulated，and the mRNA expression of I κBα was significantly up -regulated in all administration groups （P＜0.05）. Compared with TLR 4 inhibitor group ，the improvement of most of above indexes was more significant in the TLR 4 inhibitor+I. ternifolius extract group （P＜0.05）. CONCLUTIONS I. ternifolius extract could inhibit the activation of TLR 4/NF-κB/NLRP3 pathway， reduce the release of fibrosis factors and inflammatory factors ，alleviate the inflammatory injury of liver cells ，and inhibit the activation of hepatic stellate cells ，so as to protect liver cells and resist liver fibrosis .
