Abstract
Scorpion venom contains numerous bioactive peptides with potent cardiovascular effects, including bradykinin-potentiating peptides (BPPs), ion channel modulators, and cardioprotective molecules. These peptides show promise for conditions such as hypertension, cardiac injury, and arrhythmias. However, concerns regarding toxicity, immunogenicity, and off-target actions have limited their clinical development. This systematic review evaluates the therapeutic potential and safety of scorpion venom peptides for cardiovascular applications. A systematic search of PubMed, Scopus, Google Scholar, and Semantic Scholar identified 1,141 articles. Screening of 463 abstracts and full-text review of 446 eligible studies resulted in 17 publications meeting the inclusion criteria. Extracted data included mechanisms, efficacy, toxicity, and translational challenges. BPPs consistently demonstrated ACE inhibition, B2 receptor activation, and significant antihypertensive effects in animal models. Several peptides also showed cardioprotective activities by reducing oxidative stress, inflammation, and apoptosis. Ion channel-active peptides influenced cardiac electrophysiology, but many showed proarrhythmic risks due to hERG potassium channel blockade or interactions with Nav1.4/1.5 sodium channels. Structure-activity modification studies improved specificity and reduced toxicity in selected variants. Despite encouraging preclinical data, no scorpion venom peptide has progressed to clinical trials for cardiovascular indications. Major barriers include immunogenicity, instability, delivery challenges, and safety concerns. Scorpion venom peptides represent promising leads for novel cardiovascular therapeutics, particularly as antihypertensive and cardioprotective agents. However, significant toxicological and translational limitations remain. Advances in peptide engineering, targeted delivery, and clinical evaluation are crucial for safely harnessing their therapeutic potential.