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多组学分析揭示了白芍及其盐炙品在去卵巢大鼠体内抗骨质疏松的作用机制。

A Multi-Omics Analysis Reveals Anti-Osteoporosis Mechanism of Four Components from Crude and Salt-Processed Blume in Ovariectomized Rats.

机构信息

Zhejiang Technical Institute of Economics, Hangzhou 310032, China.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China.

出版信息

Molecules. 2022 Aug 6;27(15):5012. doi: 10.3390/molecules27155012.

DOI:10.3390/molecules27155012
PMID:35956964
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9370352/
Abstract

The root of Blume (AB) is a well-known traditional Chinese medicine for treating osteoporosis. Plenty of studies focused on the pharmacological mechanism of the whole extract; however, the contribution of different components to the anti-osteoporosis effect remains unknown. The aim of this study is to explore the anti-osteoporosis mechanism of different components of crude and salt-processed AB under the guidance of network pharmacology, metabolomics, and microbiomics. First, network pharmacology analysis was applied to constructing the compound-target-disease network of AB to provide a holistic view. Second, the anti-osteoporosis effects of the four components were evaluated in female Wistar rats. The subjects were divided into a normal group, a model group, a 17α-estradiol (E2)-treated group, a polysaccharide-component-treated groups, and a polysaccharide-knockout-component-treated groups. All the serum, urine, and feces samples of the six groups were collected after 16 weeks of treatment. Biochemical and microcomputed tomography (μCT) parameters were also acquired. Coupled with orthogonal partial least-squares discrimination analysis, one dimensional nuclear magnetic resonance (NMR) was used to monitor serum metabolic alterations. A total of twenty-two biomarkers, including lipids, amino acids, polyunsaturated fatty acids, glucose, and so on were identified for the different components-treated groups. Through pathway analysis, it is indicated that glyoxylate and dicarboxylate metabolism, glycine, serine, and threonine metabolism, alanine, aspartate, and glutamate metabolism, d-glutamine, and d-glutamate metabolism were the major intervened pathways. Levels of these biomarkers shifted away from the model group and were restored to normal after treatment with the four components. In addition, 16S rDNA sequencing demonstrated that the abundance of , , and bacteria was positively correlated with an anti-osteoporosis effect, whereas the abundance of was negatively correlated. The osteoprotective effect of the polysaccharide components of crude and salt-processed AB is related to the regulation of the abundance of these gut microbiota.

摘要

白芍是治疗骨质疏松症的一种常用中药。大量研究集中在全提取物的药理机制上;然而,不同成分对抗骨质疏松作用的贡献尚不清楚。本研究旨在在网络药理学、代谢组学和微生物组学的指导下,探讨白芍生品和盐制品不同成分的抗骨质疏松作用机制。首先,应用网络药理学分析构建白芍的化合物-靶标-疾病网络,提供整体视图。其次,在雌性 Wistar 大鼠中评价四种成分的抗骨质疏松作用。将实验对象分为正常组、模型组、17α-雌二醇(E2)治疗组、多糖成分治疗组和多糖敲除成分治疗组。所有六组的血清、尿液和粪便样本均在治疗 16 周后收集。还获得了生化和微计算机断层扫描(μCT)参数。结合正交偏最小二乘判别分析,一维核磁共振(NMR)用于监测血清代谢变化。共鉴定出 22 种生物标志物,包括脂质、氨基酸、多不饱和脂肪酸、葡萄糖等,用于不同成分处理组。通过途径分析,表明乙醛酸和二羧酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢、D-谷氨酰胺和 D-谷氨酸代谢是主要的干预途径。这些生物标志物的水平从模型组偏离,并在四种成分处理后恢复正常。此外,16S rDNA 测序表明, 、 和 细菌的丰度与抗骨质疏松作用呈正相关,而 细菌的丰度与抗骨质疏松作用呈负相关。白芍生品和盐制品多糖成分的骨保护作用与调节这些肠道微生物的丰度有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b9/9370352/ed3954e2b84f/molecules-27-05012-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b9/9370352/28148a0ca48e/molecules-27-05012-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b9/9370352/ed3954e2b84f/molecules-27-05012-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b9/9370352/28148a0ca48e/molecules-27-05012-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4b9/9370352/ed3954e2b84f/molecules-27-05012-g003.jpg

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