Modulation of programmed cell death by botanical drugs in Alzheimer’s disease: a review from a traditional Chinese medicine perspective

Alzheimer's disease (AD) involves dysregulation of programmed cell death (PCD) pathways, such as apoptosis, ferroptosis, autophagy, and pyroptosis. Current therapeutic options are limited, prompting interest in multi-target regulators such as metabolites derived from traditional Chinese medicine (TCM) botanical drugs. This systematic review critically evaluates recent studies on TCM-derived metabolites that modulate PCD in AD models. We identify key limitations: many metabolites are pan-assay interference metabolites (PAINS) with questionable pharmacological relevance; preclinical models inadequately recapitulate sporadic AD; and translational challenges persist in bioavailability and brain targeting. Future research requires orthogonal validation, improved delivery systems, and stage-specific strategies. This review provides a critical foundation for the development of TCM-inspired therapies for AD.