Trimethylamine-N-oxide (TMAO) is an independent risk factor for atherosclerosis. Consumption of hawthorn fruit is believed to be cardio-protective, yet whether it is able to suppress the TMAO-induced atherosclerosis remains unexplored. The present study was to investigate the effects of hawthorn fruit extract (HFE) on TMAO-exacerbated atherogenesis. Five groups of male Apolipoprotein E knock-out (ApoE−/−) mice were fed a low-fat diet (LFD), a Western high-fat diet (WD), or one of the three WDs containing 0.2% TMAO (WD + TMAO), 0.2% TMAO plus 1% HFE (WD + TMAO + L-HFE), or 0.2% TMAO plus 2% HFE (WD + TMAO + H-HFE), respectively. After 12-weeks of intervention, plasma levels of TMAO, lipid profile, inflammatory biomarkers, and antioxidant enzyme activities were measured. Atherosclerotic lesions in the thoracic aorta and aortic sinus were evaluated. The sterols and fatty acids in the liver and feces were extracted and measured. Hepatic expressions of inflammatory biomarkers and antioxidant enzymes were analyzed. Dietary TMAO accelerated atherogenesis, exacerbated inflammation, and reduced antioxidant capacities in the plasma and the liver. TMAO promoted hepatic cholesterol accumulation by inhibiting fecal excretion of acidic sterols. HFE could dose-dependently reduce the TMAO-aggravated atherosclerosis and inflammation. HFE was also able to reverse the TMAO-induced reduction in antioxidant capacity by up-regulating the expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, glutathione peroxidase 3 (GSH-Px3), and catalase (CAT) in the liver. Moreover, the hepatic cholesterol content was lowered by HFE via enhanced fecal excretion of neutral and acidic sterols. The present results indicated that HFE was able to reduce the TMAO-exacerbated atherogenesis by attenuating inflammation and improving antioxidant capacity at least in mice.

中文翻译：

---

山楂果实提取物通过抗炎和抗氧化作用减轻小鼠三甲胺-N-氧化物（TMAO）加剧的动脉粥样硬化

三甲胺-N-氧化物（TMAO）是动脉粥样硬化的独立危险因素。食用山楂果实被认为具有保护心脏的作用，但尚不能探索是否能够抑制TMAO诱导的动脉粥样硬化。本研究旨在研究山楂果实提取物（HFE）对TMAO加剧动脉粥样硬化的作用。五组雄性载脂蛋白E基因敲除（ApoE-/-）小鼠被喂以低脂饮食（LFD），西方高脂饮食（WD）或三个含0.2％TMAO的WD之一（WD + TMAO），0.2％TMAO加1％HFE（WD + TMAO + L-HFE），或0.2％TMAO加2％HFE（WD + TMAO + H-HFE）。干预12周后，测量血浆TMAO水平，脂质分布，炎性生物标志物和抗氧化酶活性。评估胸主动脉和主动脉窦的动脉粥样硬化病变。提取并测量肝脏和粪便中的固醇和脂肪酸。分析了肝脏中炎性生物标志物和抗氧化酶的表达。饮食TMAO加速了动脉粥样硬化的形成，加剧了炎症，并降低了血浆和肝脏的抗氧化能力。TMAO通过抑制粪便中酸性固醇的排泄来促进肝胆固醇的积累。HFE可以剂量依赖性地减轻TMAO加重的动脉粥样硬化和炎症。HFE还能够通过上调肝脏中包括超氧化物歧化酶1（SOD1），SOD2，谷胱甘肽过氧化物酶3（GSH-Px3）和过氧化氢酶（CAT）在内的抗氧化酶的表达来逆转TMAO诱导的抗氧化能力的降低。 。此外，HFE通过中性和酸性固醇的粪便排泄增加而降低了肝胆固醇含量。