Ginkgolide B modulates the gut-bone axis to ameliorate bone loss in ovariectomized mice.

IF 2.8 3区 医学 Q1 ORTHOPEDICS
Ning Wang, Han Yang, Xue Tong, Tong Xu, Jiamin Zhao, Yi-Kai Li
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引用次数: 0

Abstract

Scope: Estrogen deficiency post-menopause is a key driver of bone loss and is often associated with disruption of the gut-bone axis. This study explored the therapeutic potential of Ginkgolide B (GB), a natural bioactive compound from Ginkgo biloba, in estrogen deficiency-induced bone loss using ovariectomized (OVX) mice.​.

Methods: Female SPF C57BL/6J mice were randomly divided into sham-operated (Sham), OVX, and OVX+GB groups. Osteoporosis was induced by bilateral ovariectomy, and GB was administered via oral gavage for 8 weeks. Evaluations included serum biochemical markers, bone microstructure (micro-CT, histomorphometry), intestinal barrier function (histology, immunohistochemistry, and Western blot), immune cell populations (flow cytometry), and gut microbiota composition (16S rRNA gene sequencing).

Results: GB treatment significantly mitigated bone loss in OVX mice, as confirmed by micro-CT, histological, and biochemical tests. GB enhanced intestinal barrier integrity by upregulating tight junction proteins and reducing pro-inflammatory markers. Flow cytometry showed that GB restored the balance of T helper 17 (Th17) and regulatory T (Treg) cells in the mesenteric lymph node and spleen, suggesting immune regulation. Additionally, GB modulated gut microbiota composition, increasing beneficial taxa like Lactobacillaceae and Prevotellaceae. Correlation analysis indicated significant associations between microbial taxa and serum markers and bone metabolism, highlighting the role of gut microbiota in GB's therapeutic effects on osteoporosis.

Conclusion: GB is a promising natural bioactive compound for modulating bone health through the gut-bone axis, warranting further research to clarify underlying mechanisms.

银杏内酯B调节肠-骨轴以改善卵巢切除小鼠的骨质流失。
绝经后雌激素缺乏是骨质流失的一个关键驱动因素,通常与肠骨轴的破坏有关。本研究探讨了银杏内酯B (Ginkgolide B, GB)对雌激素缺乏致去卵巢(OVX)小鼠骨质流失的治疗潜力。方法:雌性SPF C57BL/6J小鼠随机分为假手术(Sham)组、OVX组和OVX+GB组。双侧卵巢切除术诱导骨质疏松,给予GB灌胃8周。评估包括血清生化指标、骨骼微观结构(显微ct、组织形态学)、肠道屏障功能(组织学、免疫组织化学和Western blot)、免疫细胞群(流式细胞术)和肠道微生物群组成(16S rRNA基因测序)。结果:显微ct、组织学和生化试验证实,GB处理可显著减轻OVX小鼠的骨质流失。GB通过上调紧密连接蛋白和减少促炎标志物来增强肠屏障的完整性。流式细胞术显示,GB能恢复肠系膜淋巴结和脾脏中辅助性T细胞17 (Th17)和调节性T细胞(Treg)的平衡,提示免疫调节作用。此外,GB调节了肠道菌群组成,增加了乳酸杆菌科和普氏菌科等有益类群。相关分析显示,肠道微生物群与血清标志物和骨代谢之间存在显著相关性,突出了肠道微生物群在GB治疗骨质疏松症中的作用。结论:GB是一种很有前景的通过肠-骨轴调节骨骼健康的天然生物活性化合物,其潜在机制有待进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
7.70%
发文量
494
审稿时长
>12 weeks
期刊介绍: Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues. Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications. JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.
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