PMID- 36737821 OWN - NLM STAT- MEDLINE DCOM- 20230209 LR - 20230209 IS - 1749-799X (Electronic) IS - 1749-799X (Linking) VI - 18 IP - 1 DP - 2023 Feb 4 TI - Deciphering the protective effect of Buzhong Yiqi Decoction on osteoporotic fracture through network pharmacology and experimental validation. PG - 86 LID - 10.1186/s13018-023-03545-7 [doi] LID - 86 AB - BACKGROUND: Osteoporotic fracture (OPF) is one of the most common skeletal diseases in an aging society. The Chinese medicine formula Buzhong Yiqi Decoction (BZYQD) is commonly used for treating OPF. However, the essential bioactive compounds and the underlying molecular mechanisms that promote fracture repair remain unclear. METHODS: We used network pharmacology and experimental animal validation to address this issue. First, 147 bioactive BZYQD compounds and 32 target genes for treating OPF were screened and assessed. A BZYQD-bioactive compound-target gene-disease network was constructed using the Cytoscape software. Functional enrichment showed that the candidate target genes were enriched in oxidative stress- and inflammation-related biological processes and multiple pathways, including nuclear factor kappa B (NF-kappaB), and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, an OPF rat model was established and treated with BZYQD. RESULTS: The results revealed that BZYQD ameliorated OPF characteristics, including femoral microarchitecture, biomechanical properties, and histopathological changes, in a dose-dependent manner. Results of enzyme-linked immunosorbent assay showed that BZYQD reduced the serum's pro-inflammatory cytokines [Tumor necrosis factor-alpha (TNF-alpha), Interleukin (IL)-1beta, and IL-6] and improved oxidative stress-related factors [glutathione (GSH) and superoxide dismutase (SOD)]. BZYQD significantly decreased the protein expression of NF-kappaB in OPF rat femurs, suppressed NF-kappaB activation, and activated the nuclear factor-erythroid factor 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) and p38 MAPK as well ERK pathways. CONCLUSIONS: Our results suggest that BZYQD could improve inflammation and oxidative stress during fracture repair by suppressing NF-kappaB and activating Nrf2/MAPK signaling pathways. CI - (c) 2023. The Author(s). FAU - Hua, Zhen AU - Hua Z AD - Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China. FAU - Dai, Shijie AU - Dai S AD - College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China. FAU - Li, Shaoshuo AU - Li S AD - Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China. FAU - Wang, Jianwei AU - Wang J AD - Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China. FAU - Peng, Hongcheng AU - Peng H AD - Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China. FAU - Rong, Yi AU - Rong Y AD - Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China. FAU - Yu, Hao AU - Yu H AD - Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China. FAU - Liu, Mingming AU - Liu M AD - Department of Orthopedics, The Second People's Hospital of Lianyungang, 41 Hailian East Road, Haizhou District, Lianyungang, 222006, Jiangsu Province, China. drliumingming@163.com. LA - eng GR - HB2020063/Top Talent Support Program for young and middle-aged people of Wuxi Health Committee/ GR - BE2021679/Social Development Program of Jiangsu Province/ PT - Journal Article DEP - 20230204 PL - England TA - J Orthop Surg Res JT - Journal of orthopaedic surgery and research JID - 101265112 RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (Nfe2l2 protein, rat) SB - IM MH - Animals MH - Rats MH - Inflammation/pathology MH - Network Pharmacology MH - NF-E2-Related Factor 2/genetics/metabolism/therapeutic use MH - *NF-kappa B/metabolism MH - *Osteoporotic Fractures/drug therapy PMC - PMC9898002 OTO - NOTNLM OT - Buzhong Yiqi Decoction OT - Network pharmacology OT - Osteoporotic fracture COIS- The authors declare that they have no competing interests. EDAT- 2023/02/05 06:00 MHDA- 2023/02/08 06:00 PMCR- 2023/02/04 CRDT- 2023/02/04 00:08 PHST- 2022/11/28 00:00 [received] PHST- 2023/01/15 00:00 [accepted] PHST- 2023/02/04 00:08 [entrez] PHST- 2023/02/05 06:00 [pubmed] PHST- 2023/02/08 06:00 [medline] PHST- 2023/02/04 00:00 [pmc-release] AID - 10.1186/s13018-023-03545-7 [pii] AID - 3545 [pii] AID - 10.1186/s13018-023-03545-7 [doi] PST - epublish SO - J Orthop Surg Res. 2023 Feb 4;18(1):86. doi: 10.1186/s13018-023-03545-7.