Journal of ethnopharmacology · 2026
Integrative target fishing and proteomics reveal the molecular targets of Abrus cantoniensis in alleviating dyslipidemia.
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Zhou Qiaowen, Lu Yuwei, Huang Mingjuan, Li Quanxin, Li Li, Chen Wenya, Fan Lanlan
Аннотация
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.
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.