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基于 UPLC/Q-TOF-MS/MS 的代谢组学揭示了秦皮的降脂作用对高脂饮食诱导的高脂血症大鼠。

UPLC/Q-TOF-MS/MS-based metabolomics revealed the lipid-lowering effect of Ilicis Rotundae Cortex on high-fat diet induced hyperlipidemia rats.

机构信息

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.

出版信息

J Ethnopharmacol. 2020 Jun 28;256:112784. doi: 10.1016/j.jep.2020.112784. Epub 2020 Mar 26.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ilicis Rotundae Cortex (IRC), a Chinese crude drug, has been widely utilized in Guangdong and Guangxi provinces of China to treat or prevent cardiovascular diseases.

AIM OF STUDY

This investigation aims to study the lipid-lowering effect of IRC, as well as the regulating effect on the endogenous metabolites in hyperlipidemia rats.

MATERIALS AND METHODS

High-fat diet induced hyperlipidemia rats were administrated with different doses of IRC extract (0.5, 1.0 and 2.0 g/kg/day) for 5 weeks. Simvastatin was used as the positive control. Body weight, serum lipid levels and histopathology of liver were evaluated. The metabolic profiles of plasma, urine and cecum content were analyzed using UPLC/Q-TOF-MS/MS-based metabolomics approach coupled with multivariate data analysis.

RESULTS

The levels of serum TC, TG, LDL-C, AST and ALT were significantly decreased and HDL-C level was increased in IRC treatment groups. The hepatic histomorphology was partially restored. 23, 26 and 15 metabolites in plasma, urine and cecum content were determined as the biological biomarkers, respectively. IRC extract could partially recover the disturbed metabolic pathways of bile acid metabolism, linoleic acid metabolism, arachidonic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycerophospholipid metabolism, synthesis and degradation of ketone bodies, sphingolipid metabolism and riboflavin metabolism.

CONCLUSION

This study demonstrated that IRC could effectively improve the serum lipids and partially restore the hepatic histomorphology. The underlying metabolic mechanism mainly included improving the metabolism of bile acids, glycerophospholipid, sphingolipid, fatty acid and amino acid. This is the first study on the lipid-lowering effect of IRC from the perspective of metabolomics.

摘要

民族药理学相关性

八角枫科植物华瓜木(IRC)是一种中国粗提物,在中国广东和广西两省广泛用于治疗或预防心血管疾病。

研究目的

本研究旨在研究 IRC 的降脂作用以及对高血脂大鼠内源性代谢物的调节作用。

材料与方法

采用高脂饮食诱导高血脂大鼠,给予 IRC 提取物(0.5、1.0 和 2.0 g/kg/天)不同剂量治疗 5 周。辛伐他汀作为阳性对照。评估体重、血清脂质水平和肝组织病理学。采用 UPLC/Q-TOF-MS/MS 代谢组学方法结合多元数据分析,分析血浆、尿液和盲肠内容物的代谢谱。

结果

IRC 治疗组血清 TC、TG、LDL-C、AST 和 ALT 水平显著降低,HDL-C 水平升高,肝组织形态学得到部分恢复。在血浆、尿液和盲肠内容物中分别确定了 23、26 和 15 种代谢物作为生物标志物。IRC 提取物可部分恢复胆汁酸代谢、亚油酸代谢、花生四烯酸代谢、牛磺酸和次牛磺酸代谢、乙醛酸和二羧酸代谢、甘油磷脂代谢、酮体的合成和降解、鞘脂代谢和核黄素代谢紊乱的代谢途径。

结论

本研究表明,IRC 可有效改善血清脂质,部分恢复肝组织形态。潜在的代谢机制主要包括改善胆汁酸、甘油磷脂、鞘脂、脂肪酸和氨基酸的代谢。这是从代谢组学角度研究 IRC 降脂作用的首次研究。

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