Functional lipidomics of Egyptian scorpions Androctonus amoreuxi and Androctonus bicolor venom reveals bioactive lipid signatures with translational potential in cancer and neuroimmune modulation

Scorpion venoms are complex biochemical arsenals, yet research has predominantly focused on neurotoxic peptides, overlooking non-protein constituents such as lipids. This study provides the first high-resolution lipidomic characterization of the venoms of two medically significant Egyptian scorpions, Androctonus amoreuxi and Androctonus bicolor, to elucidate their species-specific lipid profiles and potential bioactivities. Venoms were milked via electrostimulation. Lipids were isolated using a methyl tert-butyl ether (MTBE) protocol and analyzed using untargeted UHPLC-MS/MS in positive and negative ionization modes. Identified lipids were functionally annotated and mapped to biological pathways using the KEGG database. The venom lipidomes were remarkably diverse, with 548/527 and 479/502 distinct lipid species identified in A. amoreuxi and A. bicolor in the positive/negative modes, respectively. The dominant lipid classes included ceramides (Cer), phosphatidylcholines (PC), triglycerides (TG), and sphingomyelins (SM), with pronounced interspecies variations. A. amoreuxi venom was enriched in ceramides, while A. bicolor was characterized by higher phosphatidylethanolamine (PE) and unique phosphatidylserine (PS). KEGG analysis revealed significant enrichment in glycerophospholipid metabolism, choline metabolism in cancer, and neuroimmune signaling pathways (e.g. retrograde endocannabinoid signaling), suggesting their roles in inflammatory modulation, cell proliferation, and neuropharmacology. This study expands current understanding of scorpion venom composition by revealing its underexplored lipidomic dimension. The identified lipids were computationally predicted to be molecular participants in apoptosis, neuroimmune modulation, and oncogenic signaling. Although functional validation and potential minor hemolymph contamination warrant further investigation, these findings provide a biochemical foundation for venom-based drug discovery, positioning lipid components as emerging scaffolds for next-generation biotherapeutics development.

蝎毒是一类复杂的生化武器库，但现有研究多聚焦于神经毒性肽类，却忽略了脂质等非蛋白组分。本研究首次对两种具有医学重要性的埃及蝎——埃及杀人蝎（Androctonus amoreuxi）与双色杀人蝎（Androctonus bicolor）的毒液开展高分辨率脂质组学（lipidomic）表征，以阐明其物种特异性脂质谱与潜在生物活性。研究通过电刺激法采集蝎毒；采用甲基叔丁基醚（methyl tert-butyl ether, MTBE）法分离脂质，并通过非靶向超高效液相色谱-串联质谱（UHPLC-MS/MS）在正、负两种电离模式下完成分析。借助京都基因与基因组百科全书（KEGG）数据库，对已鉴定的脂质进行功能注释并映射至生物通路。

两种蝎毒的脂质组均呈现出极高的多样性：在正/负电离模式下，埃及杀人蝎与双色杀人蝎分别鉴定出548/527和479/502种独特脂质。优势脂质类别涵盖神经酰胺（ceramides, Cer）、磷脂酰胆碱（phosphatidylcholines, PC）、甘油三酯（triglycerides, TG）与鞘磷脂（sphingomyelins, SM），且二者存在显著的种间差异：埃及杀人蝎毒液中神经酰胺富集度更高，而双色杀人蝎则以更高水平的磷脂酰乙醇胺（phosphatidylethanolamine, PE）以及独特的磷脂酰丝氨酸（phosphatidylserine, PS）为特征。

KEGG分析显示，脂质组显著富集于甘油磷脂代谢、癌症中的胆碱代谢以及神经免疫信号通路（如逆行内源性大麻素信号通路（retrograde endocannabinoid signaling）），提示这些脂质可能参与炎症调控、细胞增殖与神经药理学过程。本研究通过揭示蝎毒液中此前未被充分探索的脂质组维度，拓展了学界对蝎毒组成的现有认知。经计算预测，已鉴定的脂质可作为分子参与者参与细胞凋亡（apoptosis）、神经免疫调控以及致癌信号通路过程。尽管仍需开展功能验证，并针对可能存在的少量血淋巴污染问题展开进一步研究，但本研究成果为基于蝎毒的药物研发提供了生化基础，同时将脂质组分确立为下一代生物治疗药物开发的新兴骨架分子。