摘要
We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity.Mice were acclimated for 1 week and randomly divided into the following groups(n=9 per group):Control,APAP,APAP+DP(100 mg·kg^–1),APAP+DP(200 mg·kg^–1),and APAP+DP(400 mg·kg^–1)groups.Mice were pretreated with DP(100,200,and 400 mg·kg^–1)by oral gavage for 7 d before being treated with 350 mg·kg^–1 APAP for 24 h to induced hepatotoxicity.Severe liver injury was observed,and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers,protein expressions levels,and liver histopathology.Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase,AST;alanine aminotransferase,ALT;alkaline phosphatase,AKP),improve redox imbalance(superoxide dismutase,SOD;glutathione,GSH;malondialdehyde,MDA),and decrease inflammatory factors(tumor necrosis factor-α,TNF-α;interleukin-1β,IL-1β).Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).Furthermore,DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein.DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1.The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration,congestion,and necrosis.Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.
We investigated the liver protective activity of dandelion polyphenols(DP) against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity. Mice were acclimated for 1 week and randomly divided into the following groups(n = 9 per group): Control, APAP, APAP + DP(100 mg·kg–1), APAP + DP(200 mg·kg–1), and APAP + DP(400 mg·kg–1) groups. Mice were pretreated with DP(100, 200, and 400 mg·kg–1) by oral gavage for 7 d before being treated with 350 mg·kg–1 APAP for 24 h to induced hepatotoxicity. Severe liver injury was observed, and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers, protein expressions levels, and liver histopathology. Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase, AST; alanine aminotransferase, ALT; alkaline phosphatase, AKP), improve redox imbalance(superoxide dismutase,SOD; glutathione, GSH; malondialdehyde, MDA), and decrease inflammatory factors(tumor necrosis factor-α, TNF-α; interleukin-1β,IL-1β). Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2). Furthermore, DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein. DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1. The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration, congestion, and necrosis. Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.
基金
supported by the National Natural Science Foundation of China(Nos.81202935 and 81773893)
the National Major Scientific and Technological Special Project of China for “Significant New Drugs Development”(No.2017ZX09301060-001)
the Natural Science Foundation of Hubei Province,China(No.2015CFB302)
Fundamental Research Funds for the Central Universities “South-Central University for Nationalities”(No.CZY20025)。
