Cell Death in Atherosclerosis: Mechanistic Insights and Therapeutic Potential of Traditional Chinese Medicine

Atherosclerosis (AS), a major cause of cardiovascular diseases, is driven by dysregulated programmed cell death (PCD) pathways. These pathways, including apoptosis, pyroptosis, ferroptosis, autophagy, and necroptosis, contribute to plaque instability. Traditional Chinese Medicine (TCM) offers a multi-targeted approach for modulating these pathways, but its molecular mechanisms in AS remain inadequately explored. This review aims to investigate the modulatory effects of TCM on PCD pathways in AS, its therapeutic potential for enhancing plaque stability, and the underlying molecular mechanisms. A narrative literature review based on relevant preclinical in vitro and in vivo studies was conducted on TCM bioactive constituents and formulas. These included studies on tonifying herbs like Radix Astragali, Radix Ginseng, and Radix Glycyrrhizae, the extracts of Radix Salviae liguliobae, and classical prescriptions such as Danshen Prescription, Huayu Qutan Recipe, Modified Taohong Siwu Decoction, Xuezhikang, Gualou Xiebai Decoction, and Mai Ji Tong Granules. The relevant data were obtained from searches of major international and Chinese biomedical databases including PubMed, Web of Science, Embase, Cochrane Library, the China Biology Medicine Database, CNKI, Wanfang, and CSTJ. The evidence indicates that these interventions modulate PCD-related pathways to thereby inhibit pathological cell death, enhance protective autophagy, and influence cellular homeostasis, inflammation, oxidative stress, lipid accumulation, and efferocytosis. TCM's multi-component nature addresses the limitations of single-target Western therapies, and thus provides a holistic strategy for AS management. However, gaps remain in the mechanistic understanding and pharmacokinetic profiles of TCM constituents that hinder clinical application. This review emphasizes TCM's potential as a complementary therapy for AS. It likewise suggests the need for further studies to identify bioactive compounds and integrate TCM with precision medicine in order to achieve better therapeutic outcomes.