Gynura procumbens aqueous extract alleviates nonalcoholic steatohepatitis through CFLAR-JNK pathway in vivo and in vitro
| Autor: | Ya-yun Liu, Wei Xu, Chun-yuan Du, Yong Chen, Ting Zhai, You Jiaojiao, Feng-mei Han |
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| Rok vydání: | 2019 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Methionine biology Gynura procumbens Lipid metabolism CYP2E1 medicine.disease_cause biology.organism_classification 030226 pharmacology & pharmacy 01 natural sciences 0104 chemical sciences CFLAR 010404 medicinal & biomolecular chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enzyme Complementary and alternative medicine chemistry medicine Phosphorylation Pharmacology (medical) Oxidative stress |
| Zdroj: | Chinese Herbal Medicines. 11:369-378 |
| ISSN: | 1674-6384 |
| DOI: | 10.1016/j.chmed.2019.09.005 |
| Popis: | Objective The present work was to investigate the protective effects of the aqueous extract of Gynura procumbens (GPAE) against nonalcoholic steatohepatitis (NASH) in mice and NCTC-1469 cells. Methods C57BL/6J mice were fed with methionine and choline-deficient (MCD) diet and administered simultaneously with GPAE (500 and 1000 mg/kg/d, respectively) by gavage for six weeks. The biomarkers of NASH in serum and liver were determined. NCTC-1469 cells were pretreated with 0.25 mmol/L palmitic acid (PA) plus 0.5 mmol/L oleic acid (OA) for 24 h or treated with adenovirus expressing short-hairpin RNA against CFLAR (Ad-shCFLAR) for 24 h and then treated with GPAE (80 and 160 µg/mL, respectively) for 24 h, and the content of cellular biomarkers of NASH was detected. Results In mice treated with MCD, GPAE could decrease the levels of serum ALT, AST, the content of hepatic TG, TC and MDA, repress the activities and protein expression of CYP2E1 and CYP4A and the phosphorylation of JNK, increase the activities of HO-1, CAT and GSH-Px, up-regulate the mRNA expression of PPARα, FABP5, CPT1α, ACOX, SCD-1, mGPAT, MTTP and the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with PA and OA, GPAE could decrease the content of cellular TG and ROS, promote the uptake of 2-NBDG, up-regulate the protein expression of CFLAR and NRF2. In NCTC-1469 cells treated with Ad-shCFLAR, GPAE up-regulated the mRNA and protein expression of CFLAR, down-regulated the phosphorylation of JNK, and increased the protein expression of NRF2 and pIRS1. Conclusion These results indicated that the activation on CFLAR-JNK pathway might be the main anti-NASH mechanism of GPAE, which on the one hand promote the β-oxidation and efflux of fatty acids in liver, and finally reduce hepatic lipid accumulation, on the other hand increase the activities of anti-oxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2, and therefore attenuates hepatic oxidative stress damage. |
| Databáze: | OpenAIRE |
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