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20S-O-Glc-DM 通过调节肠道菌群治疗代谢综合征诱导的心力衰竭。

20S-O-Glc-DM treats metabolic syndrome-induced heart failure through regulating gut flora.

机构信息

State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines & NHC Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.

出版信息

Eur J Pharmacol. 2024 Nov 5;982:176946. doi: 10.1016/j.ejphar.2024.176946. Epub 2024 Aug 27.

Abstract

Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered. C20DM, as a precursor compound of ginsenoside, is a small molecule compound obtained by biosynthetic means and is not available in natural products. In this project, we found that C20DM could improve the diversity of gut flora and elevate the expression of intestinal tight junction proteins-Occludin, Claudin, ZO-1, which inhibited the activity of the TLR4-MyD88-NF-kB pathway, and as a result, reduced myocardial inflammation and slowed down heart failure in metabolic syndrome mice. In conclusion, our study suggests that C20DM can treat heart failure by regulating gut flora, and it may be a candidate drug for treating metabolic syndrome-induced heart failure.

摘要

心力衰竭是一种多因素疾病,由代谢综合征引起的心力衰竭患者比例逐年增加。近年来,肠道菌群失调对代谢综合征和心力衰竭的影响受到了广泛关注。治疗这种疾病的药物亟待发现。C20DM 作为人参皂苷的前体化合物,是一种通过生物合成手段获得的小分子化合物,在天然产物中不存在。在本项目中,我们发现 C20DM 可以改善肠道菌群的多样性,并上调肠道紧密连接蛋白-Occludin、Claudin、ZO-1 的表达,抑制 TLR4-MyD88-NF-κB 通路的活性,从而减轻心肌炎症,减缓代谢综合征小鼠的心力衰竭进程。总之,我们的研究表明,C20DM 可以通过调节肠道菌群来治疗心力衰竭,它可能是治疗代谢综合征引起的心力衰竭的候选药物。

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