Decoding protein signaling networks in microvascular angina: the multi-target biochemical actions of traditional Chinese medicine

Although angina pectoris is among the most common conditions in cardiology, a substantial proportion of symptomatic patients exhibit persistent ischemia without flow-limiting epicardial coronary artery disease—termed ANOCA (angina with nonobstructive coronary arteries). Accumulating evidence underscores coronary microvascular dysfunction as central to ANOCA’s pathophysiology, involving molecular mechanisms such as endothelial dysfunction, oxidative stress, vascular inflammation, impaired vasodilation, microvascular remodeling, metabolic disturbance, and reduced coronary flow reserve. These interconnected pathways challenge the efficacy of single-target therapies. Traditional Chinese medicine (TCM), with its multi-target systems-based approach, offers a promising therapeutic model. Preclinical and clinical studies reveal that representative TCM formulas and bioactive compounds preserve endothelial integrity, suppress pro-inflammatory cytokines, attenuate oxidative injury, restore mitochondrial and metabolic homeostasis, stimulate angiogenesis, and improve myocardial perfusion. Such effects align with the molecular complexity of ANOCA, suggesting TCM could complement conventional cardiovascular treatments. This review synthesizes current understanding of coronary microvascular pathobiology, traces the evolution of microvascular-protective therapeutic concepts, and evaluates TCM’s mechanistic and clinical evidence base. While findings highlight TCM’s therapeutic potential, translational limitations persist—including heterogeneity in diagnostic criteria, variability in herbal formulations, methodological inconsistencies, and gaps in robust evidence. Integrating mechanistic, clinical, and translational data, this work delineates the scientific foundation, therapeutic promise, and future research directions for TCM in ANOCA-related coronary microcirculation disorders, advocating for standardized, mechanism-driven investigations to enable evidence-based integration into cardiovascular care.