摘要
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:C57 BL/6 J 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-sh CFLAR)for 24 h and then treated with GPAE(80 and 160μg/m L,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 CYP2 E1 and CYP4 A and the phosphorylation of JNK,increase the activities of HO-1,CAT and GSH-Px,up-regulate the m RNA 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-sh CFLAR,GPAE up-regulated the mRNA and protein expression of CFLAR,down-regulated the phosphorylation of JNK,and increased the protein expression of NRF2 and p IRS1.Conclusion:These results indicated that the activation on CFLAR-JNK pathway might be the main antiNASH mechanism of GPAE,which on the one hand promote theβ-oxidation and efflux of fatty acids in liver,and finally reduce hepatic lipid accumulation,on the other hand increase the activities of antioxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2,and therefore attenuates hepatic oxidative stress damage.
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: C57 BL/6 J 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-sh CFLAR) for 24 h and then treated with GPAE(80 and 160 μg/m L, 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 CYP2 E1 and CYP4 A and the phosphorylation of JNK, increase the activities of HO-1, CAT and GSH-Px, up-regulate the m RNA expression of PPARα, FABP5, CPT1α, ACOX, SCD-1, m GPAT, 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-sh CFLAR, GPAE up-regulated the m RNA and protein expression of CFLAR, down-regulated the phosphorylation of JNK, and increased the protein expression of NRF2 and p IRS1.Conclusion: These results indicated that the activation on CFLAR-JNK pathway might be the main antiNASH 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 antioxidant enzymes and inhibit the activities of ROS generation enzymes by activating NRF2, and therefore attenuates hepatic oxidative stress damage.
基金
supported by the major technological innovation project of Hubei Province(grant No.2016ACA140)
the united fund for innovation and entrepreneurship of Ministry of Education of China(grant No.201610512001).
