ReferenceID 1960

Anti-atherosclerotic effects of geraniin through the gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway in mice

Phytomedicine

Background: Cardiovascular disease is a leading cause of death, which signifies the urgent need for effective anti-atherosclerotic strategies. Gut microbiota-dependent trimethylamine-N-oxide (TMAO) is associated with ath

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Reference Id
1960
Evidence Id
18550
Core Evidence Id
18550
Source Reference Id
3932
Herb2 Reference Id
HBREF004729
Subject Paper Key
HBIN027527_35461005
Pubmed Id
35461005
Doi
10.1016/j.phymed.2022.154104
Paper Title
Anti-atherosclerotic effects of geraniin through the gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway in mice
Paper Abstract
Background: Cardiovascular disease is a leading cause of death, which signifies the urgent need for effective anti-atherosclerotic strategies. Gut microbiota-dependent trimethylamine-N-oxide (TMAO) is associated with atherosclerosis, and geraniin, a natural polyphenol with various biological activities, might play key role in this process. Purpose: We aimed to investigate the pharmacological activity of geraniin in atherosclerosis through remodeling the gut microbiota. Methods: C57BL/6J ApoE -/- mice were administrated geraniin for 12 weeks. The colon contents were analyzed via 16S rRNA sequencing. Pathological staining was performed to evaluate the atherosclerotic characteristics. Cytokine assays detected the levels of plasma inflammatory cytokines. RAW264.7 cells were cultured in vitro and treated with TMAO. Tandem Mass Tag quantitative proteomics analysis and western blot were performed to investigate the effect of TMAO in macrophages. Results: The plasma TMAO level in mice significantly decreased after geraniin intervention. The predominant intestinal microflora from geraniin-treated mice were Bacteroides (65.3%) and Firmicutes (30.6%). Pathological staining demonstrated that administration of geraniin attenuated atherosclerotic characteristics. After geraniin treatment, plasma levels of IL-1β, IL-6, and TNF-α in mice were significantly reduced, and IL-10 levels were significantly increased. Proteomics analysis demonstrated the number of differentially expressed proteins after TMAO administration. In vitro study suggested that the atherogenic effect of TMAO could be attributed to changes in CD36, transmembrane protein 106a, apolipoprotein C1, macrophage scavenger receptor types I and II, and alpha-2-macroglobulin. Conclusion: Geraniin might be an effective prospective drug against cardiovascular diseases, and the gut microbiota is a potential target to reduce the risk of atherosclerotic disease.
Journal
Phytomedicine
Publish Year
2022
Experiment Subject
mouse; raw264.7 cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Atherosclerotic Disease; Cardiovascular Disease; Cardiovascular Diseases; Atherosclerosis
Paper Title Cn
Paper Title En
Anti-atherosclerotic effects of geraniin through the gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway in mice
Bilingual Status
semi_complete