Bufadienolide, an essential member of the C-24 steroid family, is characterized by an α-pyrone positioned at C-17. As the predominantly active constituent in traditional Chinese medicine of Chansu, bufadienolide has been prescribed in the treatment of numerous ailments. It is a specifically potent inhibitor of Na⁺/K⁺ATPase with excellent anti-inflammatory activity. However, the severe side effects triggered by unbiased inhibition of the whole-body cells distributed α1-subtype of Na⁺/K⁺ATPase, restrict its future applicability. Thus, researchers have paved the road for the structural alteration of desirable bufadienolide derivatives with minimal adverse effectsviabiotransformation. In this review, we give priority to the present evidence for structural diversity, MS fragmentation principles, anti-inflammatory efficacy, and structure modification of bufadienolides derived from toads to offer a scientific foundation for future in-depth investigations and views.

Nuclear receptors (NRs) are a superfamily of ligand-dependent transcription factors that serve as pivotal regulators of gene expression in response to hormonal, metabolic, and environmental cues. They exert transcriptional control through complex interactions with co-regulators, thereby influencing gene networks involved in metabolic regulation, cell signaling, immune modulation, and homeostatic maintenance. Dysregulation of NR activity has been implicated in the pathogenesis of various metabolic and inflammatory conditions through altered gene expression and signaling cascades. This review provides an integrated overview of NR structural features and classification, elucidates their mechanisms of action in gene regulation and metabolic balance, and explores their dual roles in both physiological and pathological contexts. We further examine recent advances in NR-targeted drug discovery, including structure-based drug design, chemical biology approaches, and AI-assisted ligand development. Finally, we highlight multidisciplinary perspectives and emerging directions for NR research within the framework of precision medicine.