川芎挥发油调控单胺能神经功能防治抑郁症的作用机制研究OA

Objective:To investigate the antidepressant effects of Chuanxiong(川芎)volatile oil(CVO)and its impact on central monoaminergic neural function,thereby providing experimental evidence for the"Xingqi Jieyu"(pro-moting qi circulation and relieving depression)effect of Chuanxiong.Methods:The effects of CVO on spontaneous loco-motor activity and depressive-like behaviors in mice were evaluated using the open field test,forced swimming test(FST),and tail suspension test(TST).The influence of CVO on the monoaminergic nervous system was assessed through the 5-hydroxytryptophan(5-HTP)-induced head-twitch response,yohimbine toxicity enhancement test,and apo-morphine(APO)-induced hypothermia test.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the levels of 5-hydroxytryptamine(5-HT),dopamine(DA),and norepinephrine(NE)in the mouse hypothalamus.Immunohistochemistry was used to observe the effect of CVO on dopamine D2 receptor(D2 R)density in the mouse hypo-thalamus.Molecular docking was performed to predict the binding affinity and potential binding sites of the main chemi-cal constituents of CVO with D2 R.Results:A single administration of CVO at 1.5 g/kg or seven administrations at 4.5 g/kg significantly shortened the immobility time in the TST and FST.Administration of CVO at 0.5 g/kg for seven doses significantly increased the frequency of 5-HTP-induced head twitches and enhanced the lethality rate induced by yohimbine.A single dose of CVO at 1.5 g/kg attenuated the hyperthermic effect of haloperidol at 1.5 h post-administra-tion,while a single dose at 4.5 g/kg attenuated this effect at both 1 and 1.5 h.Administration of CVO at 0.5 and 4.5 g/kg for seven doses attenuated the hypothermic effect of APO at 1,1.5,and 2 h;CVO at 1.5 g/kg for seven do-ses attenuated this effect at 1.5 and 2 h.Furthermore,administration of CVO at 0.5 and 1.5 g/kg for seven doses sig-nificantly reduced both the DA concentration and D2 R density in the mouse hypothalamus.Molecular docking results in-dicated that the main phthalide components of CVO,such as senkyunolide A,exhibited binding energies lower than-7.5 kcal/mol with D2 R,potentially interacting at binding sites including Ser197,Phe390,and Trp386.Conclusion:CVO demonstrates significant antidepressant effects,and the underlying mechanism may involve the enhancement of 5-HT and NE neural functions,as well as the activation of hypothalamic D2R.The complete molecular mechanism and as-sociated signal transduction pathways require further in-depth investigation.