Therapeutic Promise and Toxicological Challenges of Brucine: A Comprehensive Review

Brucine, an indole alkaloid isolated from Strychnos nux-vomica , exhibits diverse pharmacological activities, including anticancer, anti-inflammatory, analgesic, and metabolic effects. However, its clinical application is limited by a narrow therapeutic index and significant neurotoxicity and hepatotoxicity. This review critically evaluates its therapeutic potential alongside toxicological and translational challenges. A PRISMA-guided literature search (2000–2026) was conducted using PubMed, Scopus, Web of Science, and Google Scholar. A total of 197 relevant studies were included based on predefined criteria. Data were qualitatively synthesized with emphasis on pharmacological mechanisms, toxicology, pharmacokinetics, and processing strategies. Brucine demonstrates multi-target pharmacological effects, including induction of apoptosis, inhibition of proliferation and angiogenesis in cancer models, suppression of inflammatory cytokines via NF-κB and MAPK pathways, and modulation of nociceptive signalling. It also shows potential in metabolic regulation and gastroprotection. Pharmacokinetic studies reveal rapid absorption, moderate bioavailability, extensive hepatic metabolism, tissue distribution, and blood–brain barrier penetration. Traditional processing methods (Pao Zhi) reduce alkaloid content but do not eliminate toxicity and may generate derivatives with uncertain safety profiles. Most evidence remains preclinical with limited clinical validation. Brucine is a pharmacologically promising yet high-risk compound. Its translation requires standardized processing, rigorous toxicological evaluation, and well-defined PK–PD relationships. Future strategies should focus on safer formulations, targeted delivery systems, and controlled clinical studies. Current evidence supports cautious scientific advancement rather than immediate therapeutic application .