Traditional Chinese Medicine Modulation of Macrophage Polarization in Inflammation Associated with Coronary Heart Disease: Mechanisms and Challenges

Abstract

: Coronary heart disease (CHD) remains a leading cause of global mortality, with unresolved inflammation constituting a major residual risk after conventional therapies. Macrophage polarization, characterized by shifts between pro-inflammatory M1 and reparative M2 phenotypes, influences vascular inflammation, plaque stability, myocardial injury, and tissue repair, making it a potential therapeutic target in CHD. Traditional Chinese Medicine (TCM) is increasingly recognized for its multi-target immunomodulatory properties. This review systematically synthesizes the current evidence on the mechanisms by which TCM formulas and active ingredients regulate macrophage polarization to modulate the inflammatory response in CHD. Importantly, the stage-specific roles of TCM during the progression of CHD (atherosclerosis, acute myocardial infarction, ischemia-reperfusion injury, and post-infarct repair) are delineated. Emerging mechanistic insights into metabolic reprogramming, mitochondrial function, and epigenetic modifications are also highlighted. However, most evidence linking TCM to macrophage polarization in CHD is derived from cellular and animal studies, while direct clinical validation remains limited. Finally, current limitations, knowledge gaps, and future directions for basic research and clinical translation are discussed. By moving beyond descriptive pathway enumeration to an integrated framework that encompasses signaling networks, disease-stage dynamics, and deep molecular mechanisms, this review aims to provide a comprehensive reference for investigators and clinicians interested in TCM-based immunomodulatory strategies for CHD.