Zhu Daoyu, Yu Hongping, Liu Pei, Yang Qianhao, Chen Yixuan, Luo Pengbo, Zhang Changqing, Gao Youshui
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Phytother Res. 2021 May;35(5):2824-2835. doi: 10.1002/ptr.7028. Epub 2021 Jan 23.
Glucocorticoid (GC) administration is one of the main causes of osteonecrosis of the femoral head (ONFH). Inflammation, especially the TLR4/NF-κB pathway, has been demonstrated to play a pivotal role in the pathogenesis of GC-induced ONFH. Calycosin, the main bioactive extract of Astragali Radix, could substantially regulate the TLR4/NF-κB pathway. Therefore, in this study, we hypothesized that calycosin could exert beneficial effects in GC-induced ONFH. In vitro, effects of calycosin on the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) were determined using Alizarin red staining, alkaline phosphatase activity examination, and osteogenic-related gene assay. Meanwhile, inflammatory cytokines were detected by enzyme-linked immunosorbent assay. In vivo, 60 male Sprague-Dawley rats were randomly separated into three groups: the control group, the methylprednisolone (MPS) group, and the MPS + calycosin group. The results showed that calycosin could significantly promote dynamic bone formation and retard TLR4/NF-κB pathway. in vivo investigations indicated that calycosin could decrease the morbidity of ONFH and alleviate pathological manifestations within the femoral head. Meanwhile, calycosin could protect osseous blood supply and facilitate dynamic bone formation. The findings collectively demonstrated that calycosin could ameliorate GC-induced ONFH in rat and might become a potential candidate for pharmaceutical prevention of this intractable disease.
糖皮质激素（GC）给药是股骨头坏死（ONFH）的主要原因之一。炎症，尤其是TLR4/NF-κB通路，已被证明在GC诱导的ONFH发病机制中起关键作用。毛蕊异黄酮，黄芪的主要生物活性提取物，可显著调节TLR4/NF-κB通路。因此，在本研究中，我们假设毛蕊异黄酮对GC诱导的ONFH可能具有有益作用。在体外，通过茜素红染色、碱性磷酸酶活性检测和成骨相关基因检测，确定毛蕊异黄酮对人骨髓间充质干细胞（hBMSCs）成骨分化的影响。同时，采用酶联免疫吸附测定法检测炎性细胞因子。在体内，将60只雄性Sprague-Dawley大鼠随机分为三组：对照组、甲基强的松龙（MPS）组和MPS+毛蕊异黄酮组。结果表明，毛蕊异黄酮可显著促进动态骨形成并抑制TLR4/NF-κB通路。体内研究表明，毛蕊异黄酮可降低ONFH的发病率，并减轻股骨头内的病理表现。同时，毛蕊异黄酮可保护骨血供并促进动态骨形成。这些研究结果共同表明，毛蕊异黄酮可改善大鼠GC诱导的ONFH，并可能成为预防这种难治性疾病的潜在药物。
