Efficacy and Mechanisms of Jiyin Fang (Granule) Against Postmenopausal Coronary Heart Disease Complicated with Osteoporosis

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Purpose To explore the efficacy and mechanisms of Jiyin Fang (JYF) against postmenopausal coronary heart disease (CHD) complicated with osteoporosis (OP). Methods Firstly, collected ingredients and relative targets of JYF from TCMSP and BATMAN-TCM database, disease targets of CHD and OP from GeneCards, TTD and OMIM database. By use of protein to protein (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, obtained core targets and mechanism pathways. Finally, preliminarily explore the pharmacological effect and major targets partly to explain the mechanism, through experiment of ovariectomized CHD with OP model rats treated with JYF. Results Total of 112 ingredients and 253 related targets of JYF, 173 disease targets common to CHD and OP were screened out. PPI network indicated 9 core targets. GO and KEGG enrichment analysis showed 20 major signal pathway. Rats experiment displayed that JYF could ameliorate the structural injury of aortic arch and femur; reduce the abnormal changes of ST segment and T wave of ECG; decrease the content of BGP, OPG, ALP, CTX, IL-6 and TNFα, increase the levels of PINP in serum; inhibit P53, MAPK, NF-κB and IKK protein expression, promote PPARG protein expression of aortic arch; inhibit NRF2, AKT protein expression and up-regulate p-STAT1, MMP9 protein expression in femur. Conclusion JYF can achieve the purpose of anti postmenopausal CHD complicated with OP. The potential mechanism may relate to P53/MAPK/NF-κB in aortic arch, and AKT/NRF2/p-STAT1 in bone, due to IL-6 and TNFα.