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薯蓣皂苷元通过调节去卵巢大鼠肠道微生物群减少骨丢失。

Diosgenin reduces bone loss through the regulation of gut microbiota in ovariectomized rats.

机构信息

Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Institute of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 100700, China.

出版信息

Gene. 2023 Jun 15;869:147383. doi: 10.1016/j.gene.2023.147383. Epub 2023 Mar 29.

DOI:10.1016/j.gene.2023.147383
PMID:37001571
Abstract

Diosgenin (DIO) is an aglycone of steroid saponins acquired from plants, including Dioscorea alata, Smilax China, and Trigonella foenum graecum, acting as an anti-osteoporosis, anti-diabetic, anti-hyperlipidemic, anti-inflammatory. Recent studies have demonstrated that DIO reduces bone loss. This study aimed to investigate the effects of DIO on the gut microbiota (GM) of ovariectomized (OVX) osteoporotic rats. Female Sprague-Dawley rats were randomly divided into sham operation (sham + vehicle group) or ovariectomy. For 12 weeks, OVX rats were treated using a vehicle (OVX + vehicle group) and DIO (OVX + DIO group). Subsequently, ELISA was conducted to determine serum estradiol levels, micro-CT scanning was performed to evaluate bone quality, and feces were collected for metagenomics sequencing to examine the structure and function of GM. Raw reads were filtered to remove chimera sequences. Operational taxonomic units (OTUs) were clustered in the filtered reads. A Venn diagram analysis was conducted to study the common and unique OTUs in the sham + vehicle, OVX + vehicle, and OVX + DIO groups. LEfSe analysis was conducted to evaluate the specific GM of the three groups. The GM functions were analyzed using the KEGG and CAZy databases. After a 12-week treatment, DIO administration prevented OVX-induced weight gain and increased the estradiol levels. DIO treatment improved the bone microstructure and structural parameters of rat tibias. Metagenomics sequencing results identified 1139, 1207, and 1235 operational taxonomic units (OTUs) in the sham + vehicle, OVX + vehicle, and OVX + DIO groups, respectively. The percentage of common OTUs was 41.2%. Treatment with DIO restored the composition of GM in OVX rats by increasing the abundance of Coriobacteriia Adlercreutzia, Romboutsia, and Romboutsia_idealis and reducing the abundance of Betaproteobacteria, Gammaproteobacteria, Methanobacteria, Bacteroides, Phocaeicola, Alistipes, Bacteroids_uniformis, Bacteroids_xylanisolvens. The anti-osteoporosis effect of DIO can be regulated through environmental information processing, organismal Systems, Cellular Processes, human diseases, metabolism, and genetic information processing. Meanwhile, treatment with DIO improved GM homeostasis by increasing the metabolism of carbohydrates, other amino acids, and glycans and reducing translation, energy metabolism, and nucleotide metabolism. DIO can reduce bone loss by regulating the structural composition and function of GM, a novel strategy for preventing osteoporosis.

摘要

薯蓣皂苷元(DIO)是一种从植物中提取的甾体皂苷苷元,包括盾叶薯蓣、菝葜和苦豆子,具有抗骨质疏松、抗糖尿病、抗高血脂、抗炎作用。最近的研究表明,DIO 可减少骨丢失。本研究旨在探讨 DIO 对去卵巢骨质疏松症大鼠肠道微生物群(GM)的影响。雌性 Sprague-Dawley 大鼠随机分为假手术(假手术+载体组)或去卵巢。12 周内,OVX 大鼠用载体(OVX+载体组)和 DIO(OVX+DIO 组)治疗。随后,通过 ELISA 测定血清雌二醇水平,通过 micro-CT 扫描评估骨质量,并收集粪便进行宏基因组测序,以检测 GM 的结构和功能。对原始读数进行过滤以去除嵌合体序列。将操作分类单元(OTUs)聚类在过滤后的读数中。进行 Venn 图分析以研究 sham+vehicle、OVX+vehicle 和 OVX+DIO 组中的常见和独特 OTUs。使用 LEfSe 分析评估三组特定的 GM。使用 KEGG 和 CAZy 数据库分析 GM 功能。经过 12 周的治疗,DIO 给药可预防 OVX 引起的体重增加并增加雌二醇水平。DIO 治疗改善了大鼠胫骨的骨微结构和结构参数。宏基因组测序结果分别在 sham+vehicle、OVX+vehicle 和 OVX+DIO 组中鉴定出 1139、1207 和 1235 个操作分类单元(OTUs)。常见 OTUs 的百分比为 41.2%。DIO 治疗通过增加 Coriobacteriia Adlercreutzia、Romboutsia 和 Romboutsia_idealis 的丰度和降低 Betaproteobacteria、Gammaproteobacteria、Methanobacteria、Bacteroides、Phocaeicola、Alistipes、Bacteroids_uniformis、Bacteroids_xylanisolvens 的丰度来恢复 OVX 大鼠 GM 的组成。DIO 的抗骨质疏松作用可通过环境信息处理、机体系统、细胞过程、人类疾病、代谢和遗传信息处理进行调节。同时,DIO 治疗通过增加碳水化合物、其他氨基酸和糖的代谢并减少翻译、能量代谢和核苷酸代谢来改善 GM 稳态。DIO 通过调节 GM 的结构组成和功能减少骨丢失,为预防骨质疏松症提供了一种新策略。

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