Abstract
Background Alisma orientalis beverage (AOB) is a Chinese traditional medicine formulated with a diversity of medicinal plants and used for treating metabolic syndrome and atherosclerosis (AS) since time ago. Given the current limited biological research on AOB, the mechanism by which AOB treats AS is unknown. This study investigats the role of AOB-induced gut microbiota regulation in the expansion of AS.MethodsWe established an AS model in male apolipoprotein E-deficient (ApoE−/−) mice that are fed with a high-fat diet (HFD), treated with numerous interventions, and evaluated the inflammatory cytokines and serum biochemical indices. The root of the aorta was stained with oil red O, and the proportion of the lesion area was quantified. Trimethylamine N-oxide (TMAO) and trimethylamine (TMA) levels in serum were evaluated through liquid chromatography with mass spectrometry. Flavin−containing monooxygenase 3 (FMO3) liver protein expression was assessed by Western blotting. 16S rDNA sequencing technique was adopted to establish the changes in the microbiota structure.ResultsAfter 8 weeks of HFD feeding, an inflammatory cytokine, and AS development expression were significantly decreased in mice treated with AOB; the same parameters in the mice treated with the antibiotics cocktail did not change. In the gut microbiota study, mice treated with AOB had a markedly different gut microbiota than the HFD-fed mice. Additionally, AOB also decreased serum TMAO and hepatic FMO3 expression.ConclusionThe antiatherosclerotic effects of AOB were found associated with changes in the content of gut microbiota and a reduction in TMAO, a gut microbiota metabolite, suggesting that AOB has potential therapeutic value in the treatment of AS.
Highlights
Despite considerable advances in its prevention, diagnosis and treatment, atherosclerosis (AS) is still a major reason for mortality around the world (Libby et al, 2011; Bentzon et al, 2014)
Dietary molecules are transformed into trimethylamine (TMA) through the action of gut microbiota, and TMA is transformed into trimethylamine N-oxide (TMAO) by hepatic flavin monooxygenase (FMO)
We examined if Alisma orientalis beverage (AOB) modifies the Flavin−containing monooxygenase 3 (FMO3) liver expression. we noticed no significant differences in levels of FMO3 in high-fat diet (HFD), Abs, and Ato groups, but the FMO3 level in the AOB treatment group (HFD: 1.28 ± 0.11Fold, high-dose Alisma orientalis beverage (AOBH): 0.92 ± 0.09Fold, low-dose Alisma orientalis beverage (AOBL): 0.93 ± 0.06Fold) (p < 0.01) decreased significantly, and the FMO3 level was reduced after antibiotics intervention combined with AOB treatment(AbsA: 0.99 ± 0.13Fold)
Summary
Despite considerable advances in its prevention, diagnosis and treatment, atherosclerosis (AS) is still a major reason for mortality around the world (Libby et al, 2011; Bentzon et al, 2014). Dietary molecules are transformed into trimethylamine (TMA) through the action of gut microbiota, and TMA is transformed into trimethylamine N-oxide (TMAO) by hepatic flavin monooxygenase (FMO). TMAO as a gut microbiota-derived metabolite, which is related to the Western diets (Barrea et al, 2019a). It may promote the development of obesity (Barrea et al, 2019b) and NAFLD (Barrea et al, 2018). Methods: We established an AS model in male apolipoprotein E-deficient (ApoE−/−) mice that are fed with a high-fat diet (HFD), treated with numerous interventions, and evaluated the inflammatory cytokines and serum biochemical indices. Flavin−containing monooxygenase 3 (FMO3) liver protein expression was assessed by Western blotting. 16S rDNA sequencing technique was adopted to establish the changes in the microbiota structure
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