Efficacy and mechanisms of Chinese herbal medicine Yiguifang Decoction in prevention and treatment of postmenopausal osteoporosis:a network pharmacology and experimental study
Objective To investigate the efficacy and mechanisms of Chinese herbal medicine Yiguifang Decoction in prevention and treatment of postmenopausal osteoporosis.Methods In network pharmacology study,the main components and targets in the prescriptions were searched through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform;the disease targets were selected from GeneCard and DrugBank.Subsequently,Cytoscape 3.7.1 was employed to construct the drug-disease target network,followed by gene ontology and Kyoto encyclopedia of genes and genomes pathway analysis.In experimental study,25 rats were divided into sham operation group,model group,Yiguifang group,estradiol group and Yiguifang+estradiol group with 5 rats in each group.Except the sham operation group,the ovariectomy was performed to establish the menopause model in last 4 groups.One month after surgery,intragastric administrations of 10 mL/(kg·d)Yiguifang Decoction,0.21 mg/(kg·d)estradiol valerate,and 10 mL/(kg·d)Yiguifang Decoction+0.21 mg/(kg·d)estradiol valerate were given to Yiguifang group,estradiol group,and Yiguifang+Estradiol group,respectively;while 10 mL/(kg·d)distilled water was given to model group and sham operation group.After 12 weeks of administration,the rats were euthanized using 2％pentobarbital sodium injection,aortic blood and the femoral bone samples were obtained.Micro-computed tomography was employed to analyze the femoral bone microstructure,including bone volume/tissue volume(BV/TV),trabecular thickness(Tb.Th),trabecular number(Tb.N),and trabecular separation(Tb.Sp).ELISA was used to measure the serum levels of procollagen type I N-terminal propeptide(PINP),tartrateresistant acid phosphatase 5b(TRACP-5b),estradiol,and follicle-stimulating hormone(FSH).Western blot analysis was conducted to evaluate the protein expression of signal transducer and activator of transcription 3(STAT3),Janus kinase(JAK),and protein kinase B(Akt)in rat femoral bone tissues.Results Network pharmacology analysis revealed that Yiguifang Decoction contained active ingredients such as quercetin,luteolin,tanshinone,naringenin,and sitosterol;and core targets included mitogen-activated protein kinase(MAPK)3,Akt1,TNF,involving signaling pathways such as MAPK and phosphatidylinositol 3-kinase(PI3K)/Akt.Animal experiments showed that compared to the model group,rats treated with Yiguifang Decoction,estradiol,and Yiguifang Decoction+estradiol exhibited increased bone microstructure parameters BV/TV,Tb.Th.Serum levels of PINP and estradiol were elevated,while FSH levels were reduced.Protein expression levels of STAT3,JAK,and Akt were decreased(all P＜0.05).Conclusion Chinese herbal medicine Yiguifang Decoction may prevent postmenopausal osteoporosis by downregulating the PI3K/Akt and JAK/STAT signaling pathways to regulate inflammation,cell apoptosis,and other factors.
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