Wang Huichao, Huang Zhongyue, Chen Guangnan, Li Yang, Liu Youwen, Gu Huijie, Cao Yujing
School of Osteopathy, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Orthopedic Institute of Henan Province, Luoyang, Henan, China.
Front Pharmacol. 2025 Apr 3;16:1548491. doi: 10.3389/fphar.2025.1548491. eCollection 2025.
Astragaloside IV (AS-IV) is one of the most potent components of Astragalus. It has been reported to promote bone formation and inhibit osteoclastogenesis, suggesting its potential as a candidate for the prevention and treatment of postmenopausal osteoporosis (PMOP). The gut microbiota may play a crucial role in mediating the effects of AS-IV.
To investigate the impact of gut microbiota on the efficacy of AS-IV in treating PMOP.
Mice were randomly divided into three groups: Sham, ovariectomy (OVX), and AS-IV-treated OVX group (80 mg/kg). Bone loss was evaluated using Micro-CT and histopathology. Immunohistochemistry assessed specific bone markers. Inflammatory levels were measured by enzyme-linked immunosorbent assay (ELISA). Intestinal barrier function was examined via colonic histopathology and immunohistochemistry. Gut microbiota composition was analyzed by 16S rDNA sequencing, while metabolomic profiling identified key metabolites. Correlation analysis was performed to explore relationships between differential bacteria, key metabolites, and bone loss.
AS-IV improved the femur microarchitecture and modulated bone turnover in OVX mice. AS-IV treatment strengthened the intestinal barrier function and decreased gut permeability. This compound reduced colonic oxidative stress and serum and bone marrow inflammatory cytokine production. 16S rDNA sequencing revealed that AS-IV modulated the gut microbiota composition, while metabolomic analysis showed its effects on pathways related to hormone biosynthesis, D-amino acid metabolism, and galactose metabolism.
This study provides new insights into the use of AS-IV for treating PMOP, highlighting the gut microbiota and its metabolites as key regulatory factors in AS-IV's therapeutic effects.
黄芪甲苷（AS-IV）是黄芪中最有效的成分之一。据报道，它可促进骨形成并抑制破骨细胞生成，表明其作为绝经后骨质疏松症（PMOP）预防和治疗候选药物的潜力。肠道微生物群可能在介导AS-IV的作用中起关键作用。
研究肠道微生物群对AS-IV治疗PMOP疗效的影响。
将小鼠随机分为三组：假手术组、卵巢切除（OVX）组和AS-IV治疗的OVX组（80mg/kg）。使用显微CT和组织病理学评估骨质流失情况。免疫组织化学评估特定的骨标志物。通过酶联免疫吸附测定（ELISA）测量炎症水平。通过结肠组织病理学和免疫组织化学检查肠道屏障功能。通过16S rDNA测序分析肠道微生物群组成，同时代谢组学分析确定关键代谢物。进行相关性分析以探索差异细菌、关键代谢物与骨质流失之间的关系。
AS-IV改善了OVX小鼠的股骨微结构并调节了骨转换。AS-IV治疗增强了肠道屏障功能并降低了肠道通透性。该化合物降低了结肠氧化应激以及血清和骨髓中炎性细胞因子的产生。16S rDNA测序显示AS-IV调节了肠道微生物群组成，而代谢组学分析表明其对与激素生物合成有关的途径、D-氨基酸代谢和半乳糖代谢有影响。
本研究为AS-IV治疗PMOP的应用提供了新的见解，强调肠道微生物群及其代谢物是AS-IV治疗效果的关键调节因素。
