期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 142, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2020.111490
关键词
Pine nut polysaccharide; Carbon tetrachloride-induced liver njury; Protection mechanism; Nrf2; Mkp1
资金
- National Key Research and Development Program of China [2016YFC050030502]
- National Natural Science Foundation of China [31900296]
- Key Research Project of the Higher Education Institute of Henan Province of China [19A550002]
Previously, we obtained a purified polysaccharide (PNP40c-1) from Pinus koraiensis pine nut and reported its protective effect on carbon tetrachloride (CCl4)-induced liver injury in vitro. The object of this study is to investigate its hepatoprotective activity in vivo and elucidate the mechanism underlying the hepatoprotection. PNP40c-1 effectively prevented the accumulation of serum liver injury biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phpsphatase and total bilirubin stimulated by CCl4. The pathological changes in PNP40c-1-treated mice livers were also markedly ameliorated. Results showed that PNP40c-1 suppressed the production of reactive oxygen species (ROS) and lipid peroxidation, upregulated Nrf2/ARE pathway and enhanced the antioxidant capacity of hepatocytes. Furthermore, the reaction between Nrf2 and ARE promoted the generation of Mkpl, which inhibited the activation of JNK induced by CCl4, and suppressed hepatocytes apoptosis by regulating the protein expression of Box, cleaved-Caspase-3 and Bcl2, exerting hepatoprotective activity. Taken together, upregulation of Nrf2/ARE pathway and suppression of JNK activation via Nrf2/ARE/Mkpl/JNK signaling pathways are the main mechanisms underlying the hepatoprotective effect of PNP40c-1 against CCl4-induced mice liver injury. These results indicated that PNP40c-1 has potential to serve as a hepatoprotective agent against chemical induced hepatotoxicity.
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