Effect mechanism of andrographolide on neuropathic pain in rats
OBJECTIVE To investigate the effect mechanism of andrographolide(Andro)on neuropathic pain(NP)in rats.METHODS Rats were randomly separated into sham operation group,model group,Andro low-dose(1 mg/kg),Andro medium-dose(5 mg/kg)and Andro high-dose(10 mg/kg)groups,and sodium ferulic acid(150 mg/kg)group,with 12 rats in each group.Except for sham operation group,other groups used the chronic sciatic nerve compression injury method to induce NP model.After modeling,each group was given relevant dose of Andro intrathecally or sodium ferulate intragastrically.The sham operation group and model group were given a constant volume of normal saline once a day for 14 consecutive days.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)of rats were detected in each group after 7 and 14 days of administration.After the last medication,the serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),prostaglandin E2(PGE2),and substance P(SP)in rats were detected in each group,and the pathological morphology of spinal cord tissue was observed.mRNA and protein expressions of ionized calcium binding adaptor molecule-1(Iba-1),growth arrest specific protein 6(Gas6),and Axl in spinal cord tissue were determined.RESULTS Compared with model group,MWT and TWL after 7 and 14 days of the administration,the mRNA and protein expressions of Gas6 and Axl after the last medication were all increased significantly in administration groups(P<0.05),while the levels of IL-6,TNF-α,PGE2 and SP,mRNA and protein expressions of Iba-1 were all decreased significantly(P<0.05);pathological injuries such as the disordered arrangement of spinal cord neurons and dilation and congestion of capillaries had been alleviated to varying degrees.Compared with sodium ferulic acid group,there was no statistically significant difference in the above indicators in the Andro high-dose group(P>0.05).CONCLUSIONS Andro may inhibit inflammatory response by activating the Gas6/Axl signaling axis,thereby alleviating NP.
andrographolideneuropathic painGas6/Axl signal axisanalgesia