ABSTRACT
Objective This study was designed to investigate the effects of corilagin on morphine-tolerant rats and discuss the reaction mechanism.Methods A rat model of chronic morphine analgesia tolerance was established.The tail-flick latency of rats was detected by using the water bath tail-flick method.The positive cell rate of ionized calcium binding adapter molecule-1(Iba-1)was detected by using immunofluorescence assay.The protein expressions of Iba-1 and mitogen-activated protein kinase(MAPK)pathway-related proteins were detected by Western blotting.The release of interleukin-6(IL-6),tumor necrosis factor alpha(TNF-α)and interleukin-1 beta(IL-1β)was detected by using enzyme-linked immunosorbent assay(ELISA).The mRNA levels of IL-6,TNF-α and IL-1β were detected by using quantitative reverse transcriptase polymerase chain reaction(qRT-PCR).Results Compared with the morphine(Mor)group,the analgesic effect of morphine in morphine+corilagin(Mor+Cor)group was strengthened with the increase of corilagin concentration.Compared with the Control group,the positive cell rate of Iba-1,Iba-1 protein expression level,levels of inflammatory factors IL-6,TNF-α,IL-1β,and the phosphorylated expression levels of MAPK signaling pathway-related proteins extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK)and p38 were significantly increased in the Mor group,which were then decreased in Mor+Cor group with the increase of corilagin con-centration.Morphine and corilagin treatment(alone or in combination)had no significant effects on the expression levels of ERK,JNK and p38.Conclusion Corilagin reduces morphine tolerance in rats by inhibiting MAPK pathway.