Targeting multiple regulated cell death pathways in acute pancreatitis: The multi-target potential of natural products from Traditional Chinese Medicine

Acute pancreatitis (AP) is a common and critical gastrointestinal disorder with significant morbidity and mortality, yet current therapeutic options remain limited. Recent advances have illuminated the central role of regulated cell death (RCD) - including apoptosis, necroptosis, pyroptosis, and ferroptosis - as a pivotal driver of pancreatic acinar cell injury and the ensuing inflammatory cascade in AP. Consequently, targeting RCD has emerged as a promising therapeutic strategy. Natural products derived from Traditional Chinese Medicine (TCM) present a particularly rich source of potential therapeutic agents due to their multi-target capabilities, high efficacy, and favorable safety profiles. This review comprehensively synthesizes evidence from the past decade to elucidate the mechanisms by which specific TCM natural products-including Emodin, Baicalin, and Wedelolactone-ameliorate AP through the precise modulation of distinct RCD pathways. We systematically detail the underlying molecular mechanisms, with a special emphasis on their multi-target pharmacology in disrupting the vicious cycle of cell death and inflammation. Finally, the review discusses the current challenges in drug development and proposes future directions for translating these promising findings into clinically viable TCM-inspired therapies for AP.