A promising approach to diabetic osteoporosis: oxymatrine’s effects on gut microbiota and osteoblasts
Abstract Objectives 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 g...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-05-01
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| Series: | Nutrition & Diabetes |
| Online Access: | https://doi.org/10.1038/s41387-025-00374-x |
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| Summary: | Abstract Objectives 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. Methods 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. Results 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. Conclusions 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. |
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| ISSN: | 2044-4052 |