基于网络药理学的补肾活血方防治去卵巢小鼠绝经后骨质疏松症的机制预测及药理学验证。

Network pharmacology-based mechanism prediction and pharmacological validation of Bushenhuoxue formula attenuating postmenopausal osteoporosis in ovariectomized mice.

机构信息

Department of Orthopedic Surgery, Li Huili Hospital Affiliated to Ningbo University, Ningbo, 315048, People's Republic of China.

Department of Orthopedic Surgery, Ningbo Yinzhou No. 2 Hospital, Ningbo, 315199, People's Republic of China.

出版信息

J Orthop Surg Res. 2023 Mar 14;18(1):200. doi: 10.1186/s13018-023-03696-7.

BACKGROUND

Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, is widely used to treat postmenopausal osteoporosis (PMOP) in China. However, the mechanism is not clear yet.

METHODS

The underlying biological processes and signaling pathways were predicted by network pharmacology. In vivo experimental study, 24 female C57BL/6 J mice were randomly divided into sham, ovariectomized (OVX) and BSHX formula groups. Mice in the latter two groups were subjected to bilateral ovariectomy, and mice in the BSHX formula group were extra treated by BSHX formula at an oral dosage of 0.2 mL/10 g for 8 weeks. The femur samples were harvested for tissue analyses including μCT assay, histology and immunohistochemical (IHC) staining of VEGF signaling.

RESULTS

A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 targets of PMOP, 64 overlapping genes were obtained. GO and KEGG enrichment analyses on these 64 genes revealed that angiogenesis and VEGF signaling were considered as the potential therapeutic mechanism of BSHX formula against PMOP. Animal experiments showed that mice in the BSHX formula-treated group presented increased bone mass, microstructural parameters, blood vessel numbers and an activation of VEGF signaling (VEGF, COX2, eNOS and CD31) compared to the OVX mice.

CONCLUSION

This study revealed that BSHX formula exerts anti-PMOP effects possibly through activating VEGF signaling-mediated angiogenesis.

背景

补肾活血方（BSHX）是一种十味草药方剂，在中国广泛用于治疗绝经后骨质疏松症（PMOP）。然而，其作用机制尚不清楚。

方法

通过网络药理学预测潜在的生物学过程和信号通路。体内实验研究中，将 24 只雌性 C57BL/6J 小鼠随机分为假手术组、去卵巢组（OVX）和 BSHX 方剂组。后两组小鼠行双侧卵巢切除术，BSHX 方剂组小鼠以 0.2 mL/10 g 的剂量灌胃 BSHX 方剂，连续 8 周。采集股骨样本进行组织分析，包括 μCT 检测、组织学和 VEGF 信号的免疫组化（IHC）染色。

结果

BSHX 方剂中共鉴定出 218 种活性成分和 274 个相关靶点，与 292 个 PMOP 靶点匹配后，得到 64 个重叠基因。这些基因的 GO 和 KEGG 富集分析表明，血管生成和 VEGF 信号通路被认为是 BSHX 方剂治疗 PMOP 的潜在作用机制。动物实验表明，与 OVX 小鼠相比，BSHX 方剂治疗组的小鼠骨量、微结构参数、血管数量和 VEGF 信号（VEGF、COX2、eNOS 和 CD31）的激活均增加。