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整合脂质组学和网络药理学分析揭示小檗碱治疗高脂血症的作用机制。

Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia.

机构信息

The Postdoctoral Research Station of Biology, Hebei Medical University, Shijiazhuang, 050017, China.

The Department of Pharmacognosy, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, China.

出版信息

J Transl Med. 2022 Sep 8;20(1):412. doi: 10.1186/s12967-022-03623-0.

Abstract

BACKGROUND

Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology.

METHODS

HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology.

RESULTS

The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP.

CONCLUSIONS

In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

摘要

背景

小檗碱(BBR)是从黄连根茎中分离得到的一种异喹啉生物碱,在中国被广泛用于治疗高脂血症(HLP)。目前,BBR 对 HLP 的疗效较为明确,但对其作用机制的研究较少。本研究旨在评估 BBR 对 HLP 仓鼠模型的潜在有益作用,并结合网络药理学研究其可能的机制和潜在的脂质生物标志物。

方法

采用高脂饮食诱导 HLP 仓鼠模型。苏木精-伊红(HE)染色法用于确定肝组织病理损伤程度。采用液相色谱-质谱联用技术分析肝组织样品的脂质代谢谱,采用多种统计分析方法筛选和鉴定脂质生物标志物。通过网络药理学揭示可能的分子机制。

结果

结果表明,有 13 种代谢物,包括 CE(16:1)、HexCer(D18:1/19:0)和 LPC(O-22:0),是 BBR 调节的生物标志物。CHPT1、PLA2G4A、LCAT 和 UGCG 被预测为 BBR 抗 HLP 的脂质相关靶点,而甘油磷脂和鞘脂代谢是 BBR 抗 HLP 的关键途径。

结论

综上所述,本研究通过网络药理学和脂质组学方法为 BBR 抗 HLP 的保护机制提供了新的见解。

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