Gynura procumbens aqueous extract alleviates nonalcoholic steatohepatitis through CFLAR-JNK pathway in vivo and in vitro
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摘要:
Abstract:
The pre-sent work was to in-ves-ti-gate the pro-tec-tive ef-fects of the aque-ous ex-tract of Gy-nura procum-bens (GPAE) against non-al-co-holic steato-hep-ati-tis (NASH) in mice and NCTC-1469 cells. Methods C57BL/?6J mice were fed with me-thio-n-ine and choline-de-fi-cient (MCD) diet and ad-min-is-tered si-mul-ta-ne-ously with GPAE (500 and 1000?mg/?kg/?d, re-spec-tively) by gav-age for six weeks. The bio-mark-ers of NASH in serum and liver were de-ter-mined. NCTC-1469 cells were pre-treated with 0.25?mmol/?L palmitic acid (PA) plus 0.5?mmol/?L oleic acid (OA) for 24?h or treated with ade-n-ovirus ex-press-ing short-hair-pin RNA against CFLAR (Ad-shCFLAR) for 24?h and then treated with GPAE (80 and 160?μg/?mL, re-spec-tively) for 24?h, and the con-tent of cel-lu-lar bio-mark-ers of NASH was de-tected. Results In mice treated with MCD, GPAE could de-crease the lev-els of serum ALT, AST, the con-tent of he-patic TG, TC and MDA, re-press the ac-tiv-i-ties and pro-tein ex-pres-sion of CYP2E1 and CYP4A and the phos-pho-ry-la-tion of JNK, in-crease the ac-tiv-i-ties of HO-1, CAT and GSH-Px, up-reg-u-late the mRNA ex-pres-sion of PPARα, FABP5, CPT1α, ACOX, SCD-1, mG-PAT, MTTP and the pro-tein ex-pres-sion of CFLAR and NRF2. In NCTC-1469 cells treated with PA and OA, GPAE could de-crease the con-tent of cel-lu-lar TG and ROS, pro-mote the up-take of 2-NBDG, up-reg-u-late the pro-tein ex-pres-sion of CFLAR and NRF2. In NCTC-1469 cells treated with Ad-shCFLAR, GPAE up-reg-u-lated the mRNA and pro-tein ex-pres-sion of CFLAR, down-reg-u-lated the phos-pho-ry-la-tion of JNK, and in-creased the pro-tein ex-pres-sion of NRF2 and pIRS1. Conclusion These re-sults in-di-cated that the ac-ti-va-tion on CFLAR-JNK path-way might be the main anti-NASH mech-a-nism of GPAE, which on the one hand pro-mote the β-ox-i-da-tion and ef-flux of fatty acids in liver, and fi-nally re-duce he-patic lipid ac-cu-mu-la-tion, on the other hand in-crease the ac-tiv-i-ties of anti-ox-i-dant en-zymes and in-hibit the ac-tiv-i-ties of ROS gen-er-a-tion en-zymes by ac-ti-vat-ing NRF2, and there-fore at-ten-u-ates he-patic ox-ida-tive stress dam-age.
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Project Supported:
major technological innovation project of Hubei Province (grant no. 2016ACA140) and the united fund for innovation and entrepreneurship of Ministry of Education of China (grant no. 201610512001)
Ya-yun Liu, Jiao-jiao You, Wei Xu, Ting Zhai, Chun-yuan Du, Yong Chen, Feng-mei Han. Gynura procumbens aqueous extract alleviates nonalcoholic steatohepatitis through CFLAR-JNK pathway in vivo and in vitro[J]. Chinese Herbal Medicines (CHM),2019,11(4):369-378
