The double-edged sword of Dioscorea bulbifera L.: Recent advances in its pharmacological benefits and hepatotoxicity, and the quest for detoxification strategies.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea bulbifera L., the dried tuber of which is known as "Huangyaozi ()" in Traditional Chinese medicine (TCM), has a history of medicinal use spanning centuries within TCM and other traditional medical systems. It is traditionally utilized to dispel nodules and reduce goiter, clear heat and resolve toxins, and cool the blood to stop bleeding. Its primary applications include the treatment of conditions such as goiter, throat obstruction, carbuncles, and inflammatory swellings. In clinical TCM practice, D. bulbifera is frequently incorporated as a key component in compound formulations aimed at managing thyroid disorders and specific inflammatory conditions.

AIM OF THE REVIEW: This review aimed to systematically delineate the dual character of D. bulbifera by synthesizing research from January 2010 to December 2025 on its phytochemistry, pharmacology, and mechanisms of liver toxicity, with a focus on evaluating detoxification strategies to reconcile its efficacy with safety.

METHODS

This comprehensive narrative review was conducted using targeted keywords related to D. bulbifera (e.g., "Huangyaozi," "Air potato") and its toxic component, Diosbulbin B (DB), across major databases including Elsevier, Web of Science, PubMed and Google Scholar.

RESULTS

Documented in both classical and modern texts, D. bulbifera possesses a well-established ethnopharmacological history. Phytochemical studies from January 2010 to December 2025 have identified 99 newly reported compounds in D. bulbifera, primarily terpenoids, steroids, and phenolics. These constituents confer a broad spectrum of pharmacological activities, including antitumor, antioxidant, antimicrobial, antidiabetic, and immunomodulatory effects, mediated through key signaling pathways such as mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2). Hepatotoxicity, the most extensively researched adverse effect, is intrinsically linked to the diterpenoid lactone DB. Its mechanism involves CYP450-mediated metabolic activation, generating reactive intermediates that trigger oxidative stress, mitochondrial dysfunction, and inhibition of hepatobiliary transporters. Guided by TCM theory, strategies such as herbal compatibility (e.g., with Angelica sinensis Radix, Glycyrrhizae Radix et Rhizoma) and processing, alongside modern approaches like co-administration with protective agents (e.g., ferulic acid), show preclinical promise in reducing toxicity while preserving efficacy.

CONCLUSION

This review clarifies the efficacy-toxicity paradox of D. bulbifera and synthesizes key detoxification strategies centered on DB. To ensure its safe modernization, future research must prioritize holistic pharmacokinetic studies, systematic clinical safety assessment using tools like the Roussel Uclaf Causality Assessment Method (RUCAM), and the adoption of innovative approaches. These include applying interdisciplinary methods (e.g., supramolecular chemistry) to elucidate detoxification mechanisms in decoctions, undertaking structural modification of the DB pharmacophore, and developing predictive biomarkers for hepatotoxicity.