Therapeutic effects of Bushen Chushi formula on knee osteoarthritis via modulation of MAPK/SLC7A11/GPX4 signaling in rats

作者：Yuanyuan Li, Hai Tang, Ming-Jiang He, Xinyue Wang, Yanbai Chen, Siye Liu, Hongmei Zhang · 发表于：Hereditas · 年份：2025 · DOI：10.1186/s41065-025-00587-1 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Osteoarthritis Treatment and Mechanisms、Bone Metabolism and Diseases

OBJECTIVE: The aim of this study is to evaluate the therapeutic efficacy of Bushen Chushi Formula (BSCSF) in a rat model of knee osteoarthritis (KOA), with a focus on the modulation of ferroptosis-related signaling pathways and inflammatory responses, and to assess its effects on cartilage integrity and subchondral bone microstructure. METHODS: A total of 66 male Sprague-Dawley rats were randomly assigned to six groups: control, model, diclofenac sodium (DCF), and BSCSF high-dose (BSCSF-H), medium-dose (BSCSF-M), and low-dose (BSCSF-L) groups. KOA was induced via intra-articular injection of monosodium iodoacetate. Following induction, BSCSF or DCF was administered orally for 4 weeks. Therapeutic outcomes were assessed through Lequesne MG scores, body weight measurements, histopathological evaluation (hematoxylin and eosin, Safranin O-Fast Green staining), and micro-computed tomography of the subchondral bone. Expression levels of ferroptosis-associated proteins (SLC7A11, GPX4, p38 MAPK, MMP-13), glutathione (GSH), and iron accumulation (Fe²⁺), as well as inflammatory cytokines (IL-1β, TNF-α), were also measured. RESULTS: When compared to the model group, rats in the BSCSF-H and BSCSF-M groups exhibited significantly lower Lequesne MG scores, improved cartilage morphology, and enhanced subchondral bone microstructure, as indicated by increased bone volume fraction, trabecular thickness, trabecular number, and connectivity density along with decreased bone surface-to-volume ra...