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血清靶向代谢组学分析吴茱萸碱对 2 型糖尿病模型大鼠作用机制。

Serum untargeted metabolomics analysis of the mechanisms of evodiamine on type 2 diabetes mellitus model rats.

机构信息

Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing 314001, China.

Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

出版信息

Food Funct. 2022 Jun 20;13(12):6623-6635. doi: 10.1039/d1fo04396j.

DOI:10.1039/d1fo04396j
PMID:35635367
Abstract

Evodiamine (EVO) is an alkaloid extracted from and has various pharmacological activities, including hypolipidemic, anti-inflammatory, anti-infective, and antitumor effects. However, the therapeutic effects of EVO on type 2 diabetes mellitus (T2DM) and the possible mechanisms remain unknown. In this study, we used a T2DM rat model using a high-fat diet (HFD) combined with streptozotocin (STZ) injections followed by treatment with EVO. First, we evaluated the therapeutic effects of EVO on T2DM rats, following which we evaluated the anti-inflammatory and anti-oxidative effects of EVO on T2DM rats. Finally, we analyzed the metabolic regulatory mechanism of EVO in T2DM rats using an untargeted metabolomics approach. The results showed that EVO treatment alleviated the hyperglycemia, hyperlipidemia, insulin resistance (IR), and pathological changes of the liver, pancreas and kidneys in T2DM rats. Moreover, EVO treatment ameliorated the oxidative stress and decreased the serum levels of pro-inflammatory cytokines in T2DM model rats. Serum untargeted metabolomics analysis indicated that the EVO treatment affected the levels of 26 metabolites, such as methionine, citric acid, cholesterol, taurocholic acid, pilocarpine, adrenic acid, and other metabolites. These metabolites were mainly related to the amino sugar and nucleotide sugar metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, and tryptophan metabolism pathways. In conclusion, EVO can reduce blood glucose and improve oxidative stress and inflammatory response in T2DM rats. These functions are related to the regulation of amino sugar and nucleotide sugar metabolism, arginine biosynthesis, arginine and proline metabolism, glutathione metabolism, and tryptophan metabolism pathways.

摘要

吴茱萸碱(EVO)是从吴茱萸中提取的一种生物碱,具有多种药理活性,包括降血脂、抗炎、抗感染和抗肿瘤作用。然而,EVO 对 2 型糖尿病(T2DM)的治疗效果及其可能的机制尚不清楚。在这项研究中,我们使用高脂饮食(HFD)联合链脲佐菌素(STZ)注射建立 2 型糖尿病大鼠模型,然后用 EVO 进行治疗。首先,我们评估了 EVO 对 2 型糖尿病大鼠的治疗作用,然后评估了 EVO 对 2 型糖尿病大鼠的抗炎和抗氧化作用。最后,我们采用非靶向代谢组学方法分析了 EVO 在 2 型糖尿病大鼠中的代谢调节机制。结果表明,EVO 治疗可改善 2 型糖尿病大鼠的高血糖、高血脂、胰岛素抵抗(IR)和肝、胰、肾的病理变化。此外,EVO 治疗可改善氧化应激,降低 2 型糖尿病模型大鼠血清中促炎细胞因子的水平。血清非靶向代谢组学分析表明,EVO 治疗影响了 26 种代谢物的水平,如蛋氨酸、柠檬酸、胆固醇、牛磺胆酸、毛果芸香碱、花生四烯酸等代谢物。这些代谢物主要与氨基糖和核苷酸糖代谢、精氨酸生物合成、精氨酸和脯氨酸代谢、谷胱甘肽代谢和色氨酸代谢途径有关。总之,EVO 可降低血糖,改善 2 型糖尿病大鼠的氧化应激和炎症反应。这些功能与调节氨基糖和核苷酸糖代谢、精氨酸生物合成、精氨酸和脯氨酸代谢、谷胱甘肽代谢和色氨酸代谢途径有关。

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