北苍术挥发油微乳解郁的药效作用和机制OA

Objective:To investigate the therapeutic effects and potential mechanisms of Atractylodes chinensis volatile oil microemulsion in relieving depression,thus establishing a theoretical foundation and a new approach for developing it as a novel adjunctive antidepressant.Methods:Sixty SD male rats were assigned into four groups:control,model(chronic unpredictable mild stress),positive drug(flupentixol hydrochloride,1.8 mg·kg-1),and low-,medium-,high-dose(16.2,32.4,64.8 mg·kg-1)A.chinensis volatile oil microemulsion.The sucrose preference test,open field test,tail suspension test,and forced swimming test were conducted to measure the sucrose preference rate,total exercise distance,average speed,resting time,tail suspension time,and swimming immobility time before and after treatment.The morphology of the rat brain tissue was visualized by hematoxylin-eosin(HE)staining.The levels of 5-hydroxytryptamine(5-HT),norepinephrine(NE),and cortisol(CORT)in the hippocampal tissue were measured by enzyme-linked immunosorbent assay(ELISA).Real-time PCR was used to detect mRNA level differences of cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),cyclic adenosine monophosphate response element-binding protein(CREB),brain-derived neurotrophic factor(BDNF),and tyrosine kinase B(TrkB)in the hippocampus.Western blot was employed to assess protein level variations of cAMP,PKA,CREB,BDNF,and TrkB in the same tissue samples.Results:Compared with that in the blank group,the body mass of rats in low-,medium-,high-dose A.chinensis volatile oil emulsion groups decreased(P<0.05),indicating that the modeling was successful.Compared with the model group,medium-,high-dose A.chinensis volatile oil emulsion shortened the tail suspension time,swimming immobility time,and resting time(P<0.05,P<0.01),while increasing the sucrose preference rate,total exercise distance,and average speed(P<0.01).No significant changes were observed in the low-dose A.chinensis volatile oil emulsion group.ELISA results indicated that CORT concentrations in the hippocampal tissue of medium and high-dose A.chinensis volatile oil emulsion groups decreased(P<0.01).In the high-dose group,5-HT and NE concentrations increased(P<0.05,P<0.01),while they had no significant changes in the low-dose group.Real-time PCR results revealed that the mRNA levels of cAMP,PKA,and CREB in the hippocampus of the medium-dose Beicangzhu volatile oil emulsion group increased(P<0.05,P<0.01),and those of cAMP,PKA,CREB,BDNF,and TrkB were upregulated in the high-dose Beicangshu volatile oil microemulsion group(P<0.01).Western blot and immunofluorescence results demonstrated that the protein levels of cAMP,PKA,and TrkB in the hippocampal tissue of the low-dose A.chinensis volatile oil microemulsion group were up-regulated(P<0.05).The medium-dose Beicangzhu volatile oil emulsion group exhibited increases in protein levels of cAMP,PKA,BDNF,and TrkB(P<0.05,P<0.01),while the high-dose group showed elevationsin protein levels of cAMP,PKA,CREB,BDNF,and TrkB(P<0.05,P<0.01).Conclusion:Beicangzhu volatile oil emulsion demonstrates certain antidepressant efficacy by inhibiting CORT expression,upregulating the expression of 5-HT,NE,cAMP,PKA,CREB,BDNF,and TrkB,activating the CREB/BDNF signaling pathway to improve the cerebral protection.