Toxic components, toxicity, and clinical management of Cascabela thevetia (L.) Lippold

Cascabela thevetia (L.) Lippold, commonly known as yellow oleander, is an evergreen shrub native to tropical and subtropical regions worldwide. This study aimed to comprehensively review the ethnomedicinal uses, cardiotoxic compounds, bioactive constituents, toxicity mechanisms, clinical features, diagnosis, and management of C. thevetia-induced cardiac toxicity, based on published case reports, research articles, and other academic literature obtained from databases such as SciFinder, PubMed, Scopus, Google Scholar, and Web of Science. C. thevetia contains potent cardiac glycosides, particularly in its seeds, which are primarily responsible for its toxicity. Although the plant has some pharmacological properties such as in vitro anticancer, antifungal, wound healing, antibacterial, antidiarrheal, anti-inflammatory, anthelminthic properties, etc., its misuse in weight loss supplements and frequent cases of accidental and intentional poisoning underscore its serious public health risks. Poisoning, commonly resulting from the ingestion of various parts (roots, leaves, flowers, and seeds), is especially prevalent among children and women in India and Sri Lanka, with incidents also reported in Mexico and the USA due to the adulteration of weight loss products. The major toxic compounds, thevetin and peruvoside, inhibit Na⁺/K⁺ ATPase, increasing intracellular Ca²⁺ levels, which enhances myocardial contractility and predisposes the heart to arrhythmias. Diagnosis is based on patient history, electrocardiogram (ECG) findings, and serum potassium levels. Immediate decontamination, such as activated charcoal administration, is crucial within 1–2 h of ingestion, followed by interventions like digoxin-specific antibody Fab therapy, atropine, and cardiac pacing. Despite reported pharmacological activities, no safe therapeutic dose of C. thevetia has been established, and its incorporation into medicinal and commercial products is not currently justified. Future research should prioritize elucidating its cardiotoxicity and safety thresholds to improve poisoning management and minimize public health risks.