Determining the targets of of licorice against postmenopausal osteoporosis: A drug target mendelian randomization study followed network pharmacology analysis

Abstract

Background We aimed to examine the main active components and mechanism of action of licorice against postmenopausal osteoporosis (PMOP) using a network pharmacology approach.And we also use the drug target mendelian Randomization (MR) to estimated the association between protein targets and PMOP, osteoporosis. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was searched for active ingredients and potential targets of licorice. Cytoscape 3.7.2 software was used to build a network between the active components of licorice and its targets. A protein–protein interaction network of the prospective targets of licorice for PMOP treatment was constructed. Enrichment studies using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were performed on the primary targets. Instrument variables obtained from eQTLGen stroage, the outcome data get from the FinnGEN and Bionbank Japan Project. Primary causal effect was estimated by inverse variance weighted. Leave-one-out analyses and co-localization were uesd to vertifited the driven effect of single nucleotide polymorphism. Results We identified 88 potent active compounds from licorice and the corresponding 226 targets of action and retrieved 2,271 osteoporosis-related genes. The main active components were quercetin, kaempferol, naringenin, formononetin, and 7-methoxy-2-methyl isoflavone; the relevant protein targets were RXRA, AKT1, PPARA, TNF, CYP1A1, F2, and STAT3. MR analyses suggested STAT3 has a positive association both with PMOP of European population (odds radio [OR] 1.27, 95% confidence interval [CI] 1.01–1.60) and osteoporosis of East Asian (OR 1.29, 95% CI 1.18–1.41). Conclusions The pharmacodynamic effects of licorice for PMOP are the result of multi-component, -target, and -pathway interactions. Licorice may affect the development of PMOP throughSTAT3 gene,tumor, lipid, and arteriosclerosis pathways; chemical carcinogenicity activation; and advanced glycation end products–receptor (AGE–RAGE) pathways, thus providing a scientific basis for using licorice against PMOP.