Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry  

作　　者：LIU Ya-lin XU Jian-jun HAN Lin-ran LIU Xiang-fei LIN Mu-hai WANG Yun XIAO Zhe HUANG Yun-ke REN Ping HUANG Xi 

机构地区：[1]Institute of Traditional Chinese Medicine-Related Comorbid Depression,Nanjing University of Chinese Medicine,Nanjing(210023),China [2]School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou(450046),China [3]Department of Outpatient,Xuzhou Central Hospital,Xuzhou,Shangdong Province(221000),China [4]Department of Obstetrics and Gynecology,Women's Hospital School of Medicine,Zhejiang University,Hangzhou(310006),China [5]Department of Geriatrics,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing(210023),China

出　　处：《Chinese Journal of Integrative Medicine》2023年第6期490-499,共10页中国结合医学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China(No.81573797,81973589,and 81072967);the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)。

摘　　要：Objective To investigate whether meranzin hydrate(MH)can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder(CSP),and further explore the potential common mechanisms.Methods Totally 120 Spraque-Dawley rats were randomly divided into 5–8 groups including sham,vehicle,fluoxetine(20 mg/kg),mosapride(10 mg/kg),CSP(30 g/kg),MH(9.18 mg/kg),[D-Lys3]-GHRP-6(Dlys,0.5 mg/kg),and MH+Dlys groups by a random number table,8 rats in each group.And 32 mice were randomly divided into wild-type,MH(18 mg/kg),growth hormone secretagogue receptor-knockout(GHSR-KO),and GHSR+MH groups,8 mice in each group.The forced swimming test(FST),open field test(OFT),tail suspension test(TST),gastric emptying(GE)test,and intestinal transit(IT)test were used to assess antidepressant and prokinetic(AP)effects after drug single administration for 30 min with absorbable identification in rats and mice,respectively.The protein expression levels of brain-derived neurotrophic factor(BDNF)and phosphorylated mammalian target of rapamycin(p-mTOR)in the hippocampus of rats were evaluated by Western blot.The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent(fMRI-BOLD).Results MH treatment improved depression-like behavior(FST,OFT)and hypomotility(GE,IT)in the acute forced swimming(FS)rats(all P<0.05),and the effects are similar to the parent formula CSP.The ghrelin antagonist[D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE(P<0.05).Similarly,MH treatment also alleviated depression-like behavior(FST,TST)in the wild-type mice,however,no effects were found in the GHSR KO mice.Additionally,administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus(both P<0.01),which were also prevented by[D-Lys3]-GHRP-6(P<0.01).Besides,3 main BOLD foci following acute FS rats implicated activity in hippocampus—thalamus—basal ganglia(HTB)circuits.The[D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci.As expected

关 键 词：Chinese medicine Gan(Liver)governing freeflow of qi COMORBIDITY depression hypomotility GHRELIN blood oxygen level-dependent 

分 类 号：R285.5[医药卫生—中药学]