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

 

By מינוזיג - MinoZig - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50413082

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

Abstract

Background and Aim

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.

Experimental Approach

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.

Key Findings

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.

Conclusions and Impact Statement

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.

Osman, A. A. K., Chai, J., Abdel-Rahman, M. A., & Xu, X. (2025). Functional lipidomics of Egyptian scorpions Androctonus amoreuxi and Androctonus bicolor venom reveals bioactive lipid signatures with translational potential in cancer and neuroimmune modulation. Toxin Reviews, 1–14. https://doi.org/10.1080/15569543.2025.2597243