PMID- 37806993 OWN - NLM STAT- MEDLINE DCOM- 20231101 LR - 20231101 IS - 2523-899X (Electronic) IS - 2523-899X (Linking) VI - 43 IP - 5 DP - 2023 Oct TI - Zuo Gui Wan Promotes Osteogenesis via PI3K/AKT Signaling Pathway: Network Pharmacology Analysis and Experimental Validation. PG - 1051-1060 LID - 10.1007/s11596-023-2782-x [doi] AB - OBJECTIVE: Osteogenesis is vitally important for bone defect repair, and Zuo Gui Wan (ZGW) is a classic prescription in traditional Chinese medicine (TCM) for strengthening bones. However, the specific mechanism by which ZGW regulates osteogenesis is still unclear. The current study is based on a network pharmacology analysis to explore the potential mechanism of ZGW in promoting osteogenesis. METHODS: A network pharmacology analysis followed by experimental validation was applied to explore the potential mechanisms of ZGW in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs). RESULTS: In total, 487 no-repeat targets corresponding to the bioactive components of ZGW were screened, and 175 target genes in the intersection of ZGW and osteogenesis were obtained. And 28 core target genes were then obtained from a PPI network analysis. A GO functional enrichment analysis showed that the relevant biological processes mainly involve the cellular response to chemical stress, metal ions, and lipopolysaccharide. Additionally, KEGG pathway enrichment analysis revealed that multiple signaling pathways, including the phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway, were associated with ZGW-promoted osteogensis. Further experimental validation showed that ZGW could increase alkaline phosphatase (ALP) activity as well as the mRNA and protein levels of ALP, osteocalcin (OCN), and runt related transcription factor 2 (Runx 2). What's more, Western blot analysis results showed that ZGW significantly increased the protein levels of p-PI3K and p-AKT, and the increases of these protein levels significantly receded after the addition of the PI3K inhibitor LY294002. Finally, the upregulated osteogenic-related indicators were also suppressed by the addition of LY294002. CONCLUSION: ZGW promotes the osteogenesis of BMSCs via PI3K/AKT signaling pathway. CI - (c) 2023. Huazhong University of Science and Technology. FAU - Yang, Shuo AU - Yang S AD - Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. FAU - Zhang, Bin AU - Zhang B AD - Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. FAU - Wang, Yu-Guo AU - Wang YG AD - Department of Traditional Chinese Medicine, Chinese PLA General Hospital, Beijing, 100853, China. FAU - Liu, Zi-Wei AU - Liu ZW AD - Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. FAU - Qiao, Bo AU - Qiao B AD - Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. FAU - Xu, Juan AU - Xu J AD - Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. newxj@hotmail.com. FAU - Zhao, Li-Sheng AU - Zhao LS AD - Department of Stomatology, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China. zhaolisheng@301hospital.com.cn. LA - eng PT - Journal Article DEP - 20231009 PL - China TA - Curr Med Sci JT - Current medical science JID - 101729993 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 0 (zuo gui wan) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM MH - *Proto-Oncogene Proteins c-akt/metabolism MH - *Phosphatidylinositol 3-Kinases/genetics/metabolism MH - Osteogenesis MH - Network Pharmacology MH - Cell Differentiation MH - Signal Transduction OTO - NOTNLM OT - PI3K/AKT signaling pathway OT - Zuo Gui Wan OT - bone marrow mesenchymal stem cells OT - network pharmacology OT - osteogenesis EDAT- 2023/10/09 00:41 MHDA- 2023/11/01 12:42 CRDT- 2023/10/08 23:06 PHST- 2023/04/24 00:00 [received] PHST- 2023/07/07 00:00 [accepted] PHST- 2023/11/01 12:42 [medline] PHST- 2023/10/09 00:41 [pubmed] PHST- 2023/10/08 23:06 [entrez] AID - 10.1007/s11596-023-2782-x [pii] AID - 10.1007/s11596-023-2782-x [doi] PST - ppublish SO - Curr Med Sci. 2023 Oct;43(5):1051-1060. doi: 10.1007/s11596-023-2782-x. Epub 2023 Oct 9.