Zhang Yang, Zhu Yiwen, Li Mengying, Zhang Minjie, Shou Dan, Tong Peijian
Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
The First Clinical School, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Nutr Diabetes. 2025 May 7;15(1):19. doi: 10.1038/s41387-025-00374-x.
Oxymatrine (OMT), a quinolizidine alkaloid derived from Sophora flavescens Ait., has demonstrated therapeutic potential in type 2 diabetes mellitus (T2DM). This study aimed to investigate its effects on diabetic osteoporosis (DOP) and explore the underlying mechanisms involving gut microbiota and osteogenic regulation.
In a rat model of T2DM, intragastric Oxymatrine was used to study trabecular bone repair through bone microstructure and histopathology analyses. Changes in gut microbiota, especially Gram-negative bacteria releasing lipopolysaccharides (LPS), were assessed via 16S rRNA sequencing. miRNA sequencing on LPS-induced rat osteoblasts, with and without Oxymatrine, explored osteoblast proliferation, mineralization, and the miR-539-5p/OGN/Runx2 pathway.
The administration of OMT resulted in an enhancement of diabetic osteopathy by reversing trabecular bone loss and modifying the composition of gut microbiota, specifically affecting Gram-negative bacteria that release LPS into the bloodstream. miRNA sequencing revealed that miR-539-5p, which was upregulated in LPS-induced ROBs, was downregulated following OMT treatment. Furthermore, OMT was found to promote osteoblast proliferation and mineralization under conditions of LPS exposure and modulate the miR-539-5p/OGN/Runx2 signaling pathway.
OMT improves diabetic osteoporosis by altering gut microbiota, decreasing LPS release, and enhancing osteoblast growth and differentiation through the miR-539-5p/OGN/Runx2 pathway, suggesting its potential as a treatment.
氧化苦参碱（OMT）是一种从苦参中提取的喹诺里西啶生物碱，已显示出对2型糖尿病（T2DM）的治疗潜力。本研究旨在探讨其对糖尿病性骨质疏松症（DOP）的影响，并探索涉及肠道微生物群和骨生成调节的潜在机制。
在T2DM大鼠模型中，通过骨微结构和组织病理学分析，使用氧化苦参碱灌胃研究小梁骨修复情况。通过16S rRNA测序评估肠道微生物群的变化，特别是释放脂多糖（LPS）的革兰氏阴性菌。对有或没有氧化苦参碱的LPS诱导的大鼠成骨细胞进行miRNA测序，探索成骨细胞增殖、矿化以及miR-539-5p/OGN/Runx2通路。
OMT给药通过逆转小梁骨丢失和改变肠道微生物群组成，特别是影响将LPS释放到血液中的革兰氏阴性菌，从而增强糖尿病性骨病。miRNA测序显示，在LPS诱导的成骨细胞中上调的miR-539-5p在OMT治疗后下调。此外，发现OMT在LPS暴露条件下促进成骨细胞增殖和矿化，并调节miR-539-5p/OGN/Runx2信号通路。
OMT通过改变肠道微生物群、减少LPS释放以及通过miR-539-5p/OGN/Runx2通路增强成骨细胞生长和分化来改善糖尿病性骨质疏松症，表明其具有治疗潜力。
