Integrative target fishing and proteomics reveal the molecular targets of Abrus cantoniensis in alleviating dyslipidemia

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of ethnopharmacology Pub Date : 2027-02-10 Epub Date: 2026-10-20 DOI:10.1016/j.jep.2026.122539

Qiaowen Zhou, Yuwei Lu, Mingjuan Huang, Quanxin Li, Li Li, Wenya Chen, Lanlan Fan

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引用次数: 0

Abstract

Ethnopharmacological relevance

Abrus cantoniensis (AC) is a traditional Chinese medicinal herb used for hepatitis, with demonstrated lipid-regulating activity. However, as a multi-component herbal system, the specific bioactive monomers and their direct protein targets remain to be elucidated.

Aim of the study

This study integrates target fishing with proteomics to capture hepatic protein targets of AC and elucidate its lipid-regulating mechanisms.

Materials and methods

Abrine, a pharmacopoeial marker compound employed as a probe, was used to synthesize abrine-functionalized magnetic beads (Fe₃O₄-SH-BP-abrine, FSBA) via photo-crosslinking for target capture from mouse liver lysates. Proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatic analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were conducted. Molecular docking, molecular dynamics (MD) simulations, surface plasmon resonance (SPR), real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and Western blotting (WB) were employed for validation.

Results

AC ameliorated hepatic steatosis in HFD-induced dyslipidemic mice. KEGG enrichment identified the pentose phosphate pathway (PPP) as the top-ranked pathway, consistent with its central role in NADPH-dependent lipid biosynthesis. Molecular docking and MD simulations predicted stable interactions between abrine and PPP enzymes. SPR verified a direct interaction between abrine and G6PD. RT-qPCR demonstrated downregulation of G6pd, Tkt, Taldo1, H6pd, and Aldoa at the mRNA level. IHC and WB consistently showed reduced protein expression of G6PD, PGD, and TKT after AC treatment.

Conclusions

Target fishing combined with proteomics uncovered AC's anti-dyslipidemic mechanism via the PPP. The identified PPP-related targets provide mechanistic insight into AC's lipid-regulating activity.

查看原文本刊更多论文

综合靶点垂钓和蛋白质组学揭示广东草缓解血脂异常的分子靶点。

民族药理学相关性：广州草（AC）是一种用于治疗肝炎的传统中药，具有调节血脂的活性。然而，作为一个多组分的草药系统，其特异性生物活性单体及其直接蛋白靶点仍有待阐明。研究目的：本研究将靶标捕捞与蛋白质组学相结合，捕获AC的肝脏蛋白靶点，并阐明其调节血脂的机制。材料与方法：以药谱标记化合物abine为探针，通过光交联法从小鼠肝脏裂解物中合成abine功能化磁珠（Fe3O4-SH-BP-abrine， FSBA）用于靶捕获。采用液相色谱-串联质谱法（LC-MS/MS）鉴定蛋白质。进行生物信息学分析，包括基因本体（GO）和京都基因与基因组百科全书（KEGG）。采用分子对接、分子动力学（MD）模拟、表面等离子体共振（SPR）、实时定量聚合酶链反应（RT-qPCR）、免疫组织化学（IHC）和Western blotting （WB）进行验证。结果：AC可改善hfd诱导的血脂异常小鼠肝脏脂肪变性。KEGG富集鉴定出戊糖磷酸途径（PPP）是最重要的途径，这与它在nadph依赖性脂质生物合成中的核心作用一致。分子对接和MD模拟预测了abine和PPP酶之间稳定的相互作用。SPR证实了abine和G6PD之间的直接相互作用。RT-qPCR显示G6pd、Tkt、Taldo1、H6pd、Aldoa mRNA水平下调。AC处理后，IHC和WB均显示G6PD、PGD和TKT蛋白表达降低。结论：靶向捕捞结合蛋白质组学揭示了AC通过PPP抗血脂异常的机制。已确定的ppp相关靶点为AC的脂质调节活性提供了机制见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of ethnopharmacology 医学-全科医学与补充医学

CiteScore

10.30

自引率

5.60%

发文量

967

审稿时长

77 days

期刊介绍： The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.