Study on the mechanism of Shuanghe decoction against steroid-induced osteonecrosis of the femoral head: insights from network pharmacology, metabolomics, and gut microbiota

作者：Kai Zhu, Wanxin Liu, Yuanyuan Peng, Xiaoqiang Wang, Zhenhao Wang, Jun Zheng, Guoying Deng, Qiugen Wang · 发表于：Journal of Orthopaedic Surgery and Research · 年份：2025 · DOI：10.1186/s13018-025-05619-0 · 被引用次数：4 · 研究领域：Bone and Joint Diseases、Spondyloarthritis Studies and Treatments、Rheumatoid Arthritis Research and Therapies

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a challenging and debilitating orthopedic condition with a rising incidence in recent years. Shuanghe Decoction (SHD), a traditional Chinese medicine formula, has shown significant efficacy in treating SONFH, though its underlying mechanisms remain unclear. PURPOSE: This study aims to elucidate the therapeutic effects and potential mechanisms of SHD on SONFH through in vivo experiments, combined with network pharmacology, metabolomics, and gut microbiota analysis. MATERIALS AND METHODS: Forty male Sprague-Dawley rats (300 ± 20 g) were randomly assigned to four groups: Control, Model, SHD-L, and SHD-H, with 10 rats each. SONFH was induced in all groups except the Control group using lipopolysaccharide and methylprednisolone. The SHD-L and SHD-H groups were treated with Shuanghe decoction at doses of 4.86 g/kg/day and 9.72 g/kg/day, respectively, for eight weeks. Bone morphology, pathological changes, and osteogenic factors were evaluated using Micro-CT, histological staining, and immunohistochemistry. Network pharmacology, metabolomics, and gut microbiota analyses were conducted to explore SHD's mechanisms. RESULTS: SHD improved bone morphology and increased osteogenic factor expression (RUNX2, OCN, COL-I). Network pharmacology indicated that metabolic pathways play a key role in SHD's therapeutic effects. Metabolomic analysis identified 14 differential metabolites, including 21-hydroxypregnenolone and ty...