Phytochemistry, Molecular Pharmacology, and Translational Drug Discovery Potential of Eleutherine bulbosa (Dayak Onion): A Systematic Review

Abstract

Background: Eleutherine bulbosa (Mill.) Urb. (Iridaceae), popularly known as Dayak onion in Kalimantan, Indonesia, occupies a distinct niche within traditional Dayak ethnomedicine, where its bulbs are employed to treat conditions ranging from breast tumours and hypertension to infectious diarrhoea. Despite well over two decades of phytochemical characterisation, the plant remains largely absent from mainstream drug discovery pipelines, representing both a scientific gap and a translational opportunity. Objective: This systematic review consolidates available evidence on the phytochemistry, molecular pharmacology, toxicological profile, and pharmacokinetic properties of E. bulbosa, with particular emphasis on mechanistic detail, quantitative bioactivity data, and translational potential. Methods: A structured literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar, following PRISMA 2020 guidelines. Of 387 records screened, 78 studies met the inclusion criteria and were subjected to qualitative synthesis. Results: The plant's bulbs elaborate a distinctive array of naphthalene, naphthoquinone, and anthraquinone derivatives, among which eleutherin, isoeleutherin, eleutherol, and eleutherinol constitute the pharmacologically dominant scaffold. Documented bioactivities span anticancer (IC50 range 12–85 µg/mL against multiple cell lines), antibacterial (MIC as low as 7.8 µg/mL against MRSA), antifungal, antioxidant, anti-inflammatory, and antidiabetic effects. Molecular targets identified include caspase-3/-9, Bcl-2/Bax, NF-κB p65, PI3K/Akt, α-glucosidase, and tyrosinase. Acute toxicity studies in rodents indicate LD50 values generally exceeding 2000 mg/kg for crude extracts, suggesting a reasonable therapeutic window. Conclusions: E. bulbosa harbours a structurally privileged chemical space with multimodal pharmacological relevance. The near-complete absence of clinical data limited pharmacokinetic characterisation, and sparse structure-activity relationship studies define the principal gaps that must be addressed before rational drug development can proceed.