文献类型：期刊文献

英文题名：Network Pharmacological Analysis and Animal Experimental Study on Osteoporosis Treatment with GuBen-ZengGu Granules

作者：Wang, Kai[1];Fan, Kai[2];Wen, Hao-Nan[1];Hai, Yun-Xiang[1];Gong, Yan-Long[3];Song, Zhi-Jing[1];Dong, Wan-Tao[3];Jiang, Yi-Wei[1];Song, Min[1]

第一作者：王恺

通信作者：Song, M[1]

机构：[1]Gansu Univ Chinese Med, Clin Coll Chinese Med, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Prov Emergency Med Aid Ctr, Lanzhou 730030, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Dept Orthoped, Affiliated Hosp, Lanzhou 730020, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Clin Coll Chinese Med, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;

年份：2023

卷号：2023

外文期刊名：EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE

收录：;Scopus(收录号：2-s2.0-85146663537);WOS:【SCI-EXPANDED(收录号:WOS:000919135800002)】；

基金：AcknowledgmentsThis study was supported by the National Natural Science Foundation of China (grant no. 81960877) and the Industrial Support Project of Gansu Higher Education Institutions (grant no. 2022CYZC-52).

语种：英文

摘要：Aim. We explored the molecular pathway and material basis of GuBen-ZengGu granules (GBZGG) in treating osteoporosis using network pharmacology and animal experiments. Methods. The effective active components and potential targets of GBZGG were obtained from the TCMSP database and BATMAN-TCM database. Disease-related genes were obtained from GeneCard, NCBI, and DisGeNET. Next, a protein interaction network was established using the STRING database, and core genes were screened using the MCODE module. Cytoscape 3.8.0 was used to construct the network of component-disease-pathway-target, and KEGG pathway enrichment analyses were performed using the clusterProfiler R package to predict the mechanism of GBZGG in treating osteoporosis. An osteoporosis rat model was established by ovarian excision (OVX), and the partial results of network pharmacology were experimentally verified. Results. Pharmacodynamic results showed that GBZGG increased bone mineral density (BMD) and significantly improved the indexes of femur microstructure in model rats. The network pharmacology results showed that quercetin, luteolin, stigmasterol, angelicin, kaempferol, bakuchiol, bakuchiol, 7-O-methylisomucronulatum, isorhamnetin, formononetin, and beta-sitosterol are the major components of GBZGG, with MAPK1, AKT1, JUN, HSP90AA1, RELA, MAPK14, ESR1, RXRA, FOS, MAPK8, NCOA1, MYC, and IL-6 as its core targets for treating osteoporosis. Biological effects could be exerted by regulating the signaling pathways of fluid shear stress and the signaling pathways of atherosclerosis, advanced glycation end products (AGE-RAGE) of diabetic complications, prostate cancer, interleukin (IL-17), tumor necrosis factor (TNF), hepatitis B, mitogen-activated protein kinase (MAPK), etc. The results of animal experiments showed that GBZGG could reduce the serum levels of IL-6 and TNF-alpha, increase the expression of bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2) protein, and inhibit the activity of extracellular-regulated protein kinases (ERK1/2) and phosphorylation ERK1/2 (p-ERK1/2) protein. Conclusion. GBZGG reduces the expression of ERK1/2 and p-ERK1/2 proteins and mRNAs through the inhibitory effects on IL-6 and TNF-alpha and negatively regulates the MAPK/ERK signaling pathway. The osteoporosis model showed that it effectively improved the loss of bone mass and destruction of bone microstructure in rats and maintained a positive balance for bone metabolism.