Ginsenoside Rb1 ameliorates heart failure through DUSP-1-TMBIM-6-mediated mitochondrial quality control and gut flora interactions.

Autor: Pu X; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China., Zhang Q; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China., Liu J; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China., Wang Y; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China., Guan X; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China., Wu Q; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China., Liu Z; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. Electronic address: ZhimingLiuGAM@163.com., Liu R; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. Electronic address: liuruxiu1@163.com., Chang X; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China. Electronic address: xingchang_tcm@outlook.com.
Jazyk: angličtina
Zdroj: Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Sep; Vol. 132, pp. 155880. Date of Electronic Publication: 2024 Jul 20.
DOI: 10.1016/j.phymed.2024.155880
Abstrakt: Background: There is currently no specific therapeutic drug available for heart failure in clinical practice. Numerous studies have validated the efficacy of Ginsenoside Rb1, an active component found in various herbal remedies used for heart failure treatment, in effectively ameliorating myocardial ischemia. However, the precise mechanism of action and molecular targets of Ginsenoside Rb1 remain unclear.
Purpose: This study aims to explore the molecular mechanisms through which Ginsenoside Rb1 synergistically modulates the gut flora and mitochondrial quality control network in heart failure by targeting the DUSP-1-TMBIM-6-VDAC1 axis.
Study Design: This study utilized DUSP-1/VDAC1 knockout (DUSP-1 -/- /VDAC1 -/- ) and DUSP-1/VDAC1 transgenic (DUSP-1 +/+ /VDAC1 +/+ ) mouse models of heart failure, established through Transverse Aortic Constriction (TAC) surgery and genetic modification techniques. The mice were subsequently subjected to treatment with Ginsenoside Rb1.
Methods: A series of follow-up multi-omics analyses were conducted, including assessments of intestinal flora, gene transcription sequencing, single-cell databases, and molecular biology assays of primary cardiomyocytes, to investigate the mechanism of action of Ginsenoside Rb1.
Results: Ginsenoside Rb1 was found to have multiple regulatory mechanisms on mitochondria. Notably, DUSP-1 was discovered to be a crucial molecular target of Ginsenoside Rb1, controlling both intestinal flora and mitochondrial function. The regulatory effects of DUSP-1 on inflammation and mitochondrial quality control were mediated by changes in TMBIM-6 and VDAC1. Furthermore, NLRP3-mediated inflammatory responses were found to interact with mitochondrial quality control, exacerbating myocardial injury under stress conditions. Ginsenoside Rb1 modulated the DUSP-1-TMBIM-6-VDAC1 axis, inhibited the release of pro-inflammatory factors, altered the structural composition of the gut flora, and protected impaired heart function. These effects indirectly influenced the crosstalk between inflammation, mitochondria, and gut flora.
Conclusion: The DUSP-1-TMBIM-6-VDAC1 axis, an upstream pathway regulated by Ginsenoside Rb1, is a profound mechanism through which Ginsenoside Rb1 improves cardiac function in heart failure by modulating inflammation, mitochondria, and gut flora.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier GmbH. All rights reserved.)
Databáze: MEDLINE
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