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二氢青蒿素对小鼠肠道微生物组的影响。

Effects of dihydroartemisinin on the gut microbiome of mice.

机构信息

Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong 510006, P.R. China.

The First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, P.R. China.

出版信息

Mol Med Rep. 2020 Aug;22(2):707-714. doi: 10.3892/mmr.2020.11165. Epub 2020 May 20.

Abstract

Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin, which has been found to exhibit a broad range of biological activities, excluding antimalarial effects; however its effects on the gut microbiota remain poorly understood. The present study aimed to investigate the effects of DHA on the gut microbiome in mice and to determine its potential biological and pharmaceutical activities through its alteration of the gut microbiota. Serum glucose, triglyceride (TG), total cholesterol, lipopolysaccharide, high density lipoprotein‑cholesterol, low density lipoprotein‑cholesterol, alanine aminotransferase and aspartate aminotransferase levels in mice treated with DHA were analyzed using the corresponding detection kits. In addition, hematoxylin and eosin staining was performed to determine the pathological effects of DHA on the liver, kidney and intestinal tissues of mice, and the effects of DHA on the gut microbiome were analyzed using 16S ribosomal (r)DNA gene analysis. The results demonstrated that the TG serum levels of mice treated with DHA were significantly decreased compared with the control group. Furthermore, 16S rDNA gene analysis demonstrated that the bacterial diversity of mice treated with DHA was enriched compared with the control group. The DHA group exhibited increased numbers of Firmicutes and Saccharibacteria, and decreased Deferribacteres and Actinobacteria compared with the control group at the phylum level. Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis also revealed that the signaling pathways associated with 'Energy metabolism' and 'Nucleotide metabolism' were upregulated, whereas the signaling pathways associated with 'Infectious diseases and 'Neurodegenerative diseases' were downregulated in the DHA group compared with the control group. In conclusion, the findings of the present study indicated that DHA may significantly decrease the serum TG levels and alter the gut microbiota, which suggested its potential to be used for the treatment of hyperlipidemia, inflammatory and neurodegenerative disorders.

摘要

二氢青蒿素(DHA)是青蒿素的半合成衍生物,已发现其具有广泛的生物活性,不包括抗疟作用;然而,其对肠道微生物群的影响仍知之甚少。本研究旨在探讨 DHA 对小鼠肠道微生物群的影响,并通过改变肠道微生物群来确定其潜在的生物学和药物活性。使用相应的检测试剂盒分析了 DHA 处理小鼠的血清葡萄糖、甘油三酯(TG)、总胆固醇、脂多糖、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平。此外,通过苏木精和伊红染色来确定 DHA 对小鼠肝、肾和肠道组织的病理影响,并通过 16S 核糖体(r)DNA 基因分析来分析 DHA 对肠道微生物群的影响。结果表明,与对照组相比,DHA 处理小鼠的血清 TG 水平显著降低。此外,16S rDNA 基因分析表明,与对照组相比,DHA 处理小鼠的细菌多样性得到了丰富。与对照组相比,DHA 组在门水平上表现出厚壁菌门和 saccharibacteria 的数量增加,而脱硫杆菌门和放线菌门的数量减少。京都基因与基因组百科全书信号通路富集分析还表明,与对照组相比,DHA 组与“能量代谢”和“核苷酸代谢”相关的信号通路上调,而与“传染病”和“神经退行性疾病”相关的信号通路下调。综上所述,本研究结果表明,DHA 可能显著降低血清 TG 水平并改变肠道微生物群,这表明其在治疗高脂血症、炎症和神经退行性疾病方面具有潜在的应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b28/7339414/6bf269d78d7e/MMR-22-02-0707-g00.jpg

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