Exploring the mechanism of action of Xiaoyao pill in the treatment of osteoporosis based on network pharmacology and animal experiments
Objective:To investigate the therapeutic effects of Xiaoyao pill on bone structure and morphology in mice with ovariectomy-induced osteoporosis,as well as the changes and molecular mechanism of AGES/RAGE signaling pathway based on network pharmacology and animal experiments.Methods:TCMSP and other databases were used to search for the drug ingredi-ents of Xiaoyao pill and their related targets."Osteoporosis"was used as the keyword in GeneCards and other databases to search for osteoporosis disease-related targets;Wayne diagrams were made to obtain intersection targets;Finally,GO and KEGG enrich-ment analyses were performed on drug-disease intersection targets through DAVID database,and the enrichment results were vi-sualized.Additionally,mice model with ovariectomy-induced osteoporosis were established,and the influence of Xiaoyao pill on osteogenic differentiation was detected by CT scanning,HE staining and immunohistochemistry,and the prediction results of net-work pharmacological signaling pathways were verified.Results:Eight core active ingredients in Xiaoyao pill were found,namely chaihu,angelica,white peony,fried baiju,poria,licorice,peppermint and ginger.A total of 225 key targets of Xiaoyao Pill and OP were predicted,and these key targets were mainly involved in regulating the AGEs/RAGE signaling pathway,IL-17 signal-ing pathway,TNF signaling pathway,etc.In the mouse osteoporosis model,Xiaoyao pill could effectively increase the expression of ALP and COL-1 osteogenic transcription factors(P<0.05),and downregulate the expression of rage and IL-6,key proteins of the AGEs/RAGE signaling pathway(P<0.05).Conclusion:Xiaoyao pill can effectively improve the bone morphological struc-ture in mice with osteoporosis and has anti-ovary osteoporosis effect,and its mechanism may be related to inhibition of AGES/RAGE signaling pathway and increase osteogenic marker genes ALP and COL-1.