Department of Orthopedics, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, China.
College of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
J Orthop Surg Res. 2023 Feb 4;18(1):86. doi: 10.1186/s13018-023-03545-7.
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.
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-κB), and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, an OPF rat model was established and treated with BZYQD.
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-α), Interleukin (IL)-1β, and IL-6] and improved oxidative stress-related factors [glutathione (GSH) and superoxide dismutase (SOD)]. BZYQD significantly decreased the protein expression of NF-κB in OPF rat femurs, suppressed NF-κB activation, and activated the nuclear factor-erythroid factor 2-related factor (Nrf2)/heme oxygenase 1 (HO-1) and p38 MAPK as well ERK pathways.
Our results suggest that BZYQD could improve inflammation and oxidative stress during fracture repair by suppressing NF-κB and activating Nrf2/MAPK signaling pathways.
骨质疏松性骨折（OPF）是老龄化社会中最常见的骨骼疾病之一。中药方剂补中益气汤（BZYQD）常用于治疗 OPF。然而，促进骨折修复的基本生物活性化合物和潜在分子机制仍不清楚。
我们使用网络药理学和实验动物验证来解决这个问题。首先，筛选和评估了 147 种 BZYQD 生物活性化合物和 32 个治疗 OPF 的靶基因。使用 Cytoscape 软件构建了 BZYQD-生物活性化合物-靶基因-疾病网络。功能富集表明，候选靶基因富集在氧化应激和炎症相关的生物学过程和多种途径中，包括核因子 kappa B（NF-κB）和丝裂原激活蛋白激酶（MAPK）信号通路。此外，建立了 OPF 大鼠模型并给予 BZYQD 治疗。
结果表明，BZYQD 以剂量依赖的方式改善了股骨微观结构、生物力学特性和组织病理学变化等 OPF 特征。酶联免疫吸附试验结果表明，BZYQD 降低了血清中促炎细胞因子[TNF-α、IL-1β和 IL-6]，改善了氧化应激相关因子[谷胱甘肽（GSH）和超氧化物歧化酶（SOD）]。BZYQD 显著降低了 OPF 大鼠股骨中 NF-κB 的蛋白表达，抑制了 NF-κB 的激活，并激活了核因子-红细胞生成素 2 相关因子（Nrf2）/血红素加氧酶 1（HO-1）和 p38 MAPK 以及 ERK 通路。
我们的结果表明，BZYQD 通过抑制 NF-κB 和激活 Nrf2/MAPK 信号通路，可改善骨折修复过程中的炎症和氧化应激。
