Data_Sheet_1_Effects of Xinjiang wild cherry plum (Prunus divaricata Ledeb) anthocyanin-rich extract on the plasma metabolome of atherosclerotic apoE-deficient mice fed a high-fat diet.pdf

It is well-known that many vegetables and fruits have abundant polyphenols, such as anthocyanins, which benefit many cardiovascular diseases due to their anti-oxidative and anti-inflammatory effects. To explore the protective effect of anthocyanin on atherosclerosis from a metabolic perspective, alterations in plasma metabolic profiling of apoE-deficient (apoE–/–) mice in response to treatment with anthocyanin extracts derived from Xinjiang wild cherry plum (Prunus divaricata Ledeb) peel was investigated through UHPLC-Q-TOF/MS. The mice were fed with a normal diet or high-fat diet supplementation with or without anthocyanin extracts (ACNE, 75, 150, 250 mg/kg body weight) for 18 weeks, corresponding to control (Con), model (Mod), and treatment group (LD, low dose; MD, medium dose; HD, high dose), respectively, along with a positive control group (posCon, treatment with Atorvastatin, 0.003 mg/kg body weight). The results showed that ACNE could significantly enhance the antioxidant capacity and lower the plasma lipid, but have no evident influence on the body weight of apoE–/– mice. A series of differential metabolites, predominantly related to lipid metabolism, were identified, including docosahexaenoic acid, palmitoyl ethanolamide, stearoylcarnitine, L-palmitoylcarnitine, indoxyl sulfate (IS), 1-palmitoyl-lysophosphatidylcholine, phenylacetylglycine (PAGly), and so on. Among these, both IS and PAGly were host-microbial metabolites. These differential metabolites were mainly enriched in the pathway of glycerophospholipid metabolism and linoleic acid metabolism. Several important enzymes related to glycerophospholipid metabolisms such as LCAT, LPCAT, GPCPD1, PLA2G1B, PPARG, LIPE, PNPLA2, AGPAT1, and ENPP2 were recognized as underlying targets for anti-atherogenic effects of ACNE. These findings suggest that ACNE derived from Xinjiang wild cherry plum exhibits protective effects against atherosclerosis via modulating glycerophospholipid metabolism.

众所周知，诸多果蔬富含多酚类物质，其中花青素(anthocyanins)凭借抗氧化与抗炎特性，对多种心血管疾病具有防护益处。为从代谢组学视角探究花青素对动脉粥样硬化的防护作用，本研究采用超高效液相色谱-串联四极杆飞行时间质谱(UHPLC-Q-TOF/MS)，分析了载脂蛋白E缺陷（apoE–/–）小鼠经新疆野生樱桃李(Prunus divaricata Ledeb)果皮源花青素提取物(ACNE)处理后的血浆代谢谱变化。实验小鼠被分为以下组别：普通膳食喂养的对照组(Con)、高脂膳食喂养的模型组(Mod)、分别添加75、150、250 mg/kg体重剂量ACNE的高脂膳食治疗组（低剂量组LD、中剂量组MD、高剂量组HD），以及给予阿托伐他汀(Atorvastatin，0.003 mg/kg体重)的阳性对照组(posCon)，所有小鼠均连续干预18周。研究结果显示，ACNE可显著提升apoE–/–小鼠的抗氧化能力、降低血浆脂质水平，但对其体重无明显影响。本研究鉴定出一系列主要与脂质代谢相关的差异代谢物，包括二十二碳六烯酸(docosahexaenoic acid)、棕榈酰乙醇酰胺、硬脂酰肉碱、L-棕榈酰肉碱、吲哚硫酸酯(IS)、1-棕榈酰溶血磷脂酰胆碱、苯乙酰甘氨酸(PAGly)等。其中，吲哚硫酸酯(IS)与苯乙酰甘氨酸(PAGly)均为宿主-微生物共代谢产物。上述差异代谢物主要富集于甘油磷脂代谢与亚油酸代谢通路。多项与甘油磷脂代谢相关的关键酶，包括卵磷脂胆固醇酰基转移酶(LCAT)、溶血磷脂酰胆碱酰基转移酶(LPCAT)、甘油磷酸胆碱磷酸二酯酶1(GPCPD1)、磷脂酶A2组1B(PLA2G1B)、过氧化物酶体增殖物激活受体γ(PPARG)、激素敏感性脂肪酶(LIPE)、patatin样磷脂酶结构域2(PNPLA2)、1-酰基甘油-3-磷酸O-酰基转移酶1(AGPAT1)以及外核苷酸焦磷酸酶/磷酸二酯酶2(ENPP2)，被认定为ACNE抗动脉粥样硬化作用的潜在靶点。本研究结果表明，新疆野生樱桃李来源的ACNE可通过调控甘油磷脂代谢发挥抗动脉粥样硬化的防护作用。