Ageing Res Rev. 2026 Jun 30:103222. doi: 10.1016/j.arr.2026.103222. Online ahead of print.
ABSTRACT
Myocardial hypertrophy is a critical pathological basis for the progression of numerous cardiovascular diseases towards heart failure. Programmed cell death (PCD) including apoptosis, autophagy, pyroptosis, ferroptosis and necroptosis, play a pivotal role in both the initiation and advancement of myocardial hypertrophy. These processes contribute to myocardial cell damage and hypertrophy through the induction of oxidative stress, inflammatory responses, and other associated pathways. Natural products, which encompass a range of dietary components and possess medicinal properties, have emerged as a promising area for the treatment of myocardial hypertrophy, due to their multi-pathway and low-toxicity profiles. These natural products systematically inhibit myocardial cell apoptosis, modulate the autophagy pathway and dynamically regulate its activation and inhibition states, restoring myocardial cell homeostasis, regulate pyroptosis by inhibiting the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, as well as the cleavage and activation of Gasdermin D (GSDMD). Furthermore, they suppress ferroptosis through regulation of iron metabolism, reducing free iron accumulation, enhancing antioxidant defenses, and inhibiting lipid peroxidation. Additionally, they inhibit necroptosis by modulating the key execution molecules involved in this process, ultimately delay the progression of myocardial hypertrophy. Thus, natural products that target PCD offer innovative concepts and potential candidate molecules for the prevention and treatment of myocardial hypertrophy in the context of drug development.
PMID:42379316 | DOI:10.1016/j.arr.2026.103222