Traditional Chinese medicine and RhoA/ROCK signaling in myocardial ischemia/reperfusion injury: a narrative review of preclinical evidence

Ischemic heart disease is one of the major diseases that affect human health, and it has high morbidity and mortality rates globally. The primary clinical strategy for its treatment is prompt restoration of blood supply to the ischemic myocardium. Nevertheless, reperfusion of blood flow can exacerbate myocardial damage, leading to myocardial ischemia/reperfusion injury (MIRI). RhoA/rho-associated protein kinase (ROCK) signaling plays a pivotal role in cardiovascular diseases and is a candidate therapeutic target in MIRI. However, its role is bidirectional: the intensity and duration of activation, the phase of ischemia and reperfusion, the cell type in which the signal arises, and the downstream effector engaged together determine whether RhoA signaling injures or protects the myocardium. Protection is carried by branches acting through protein kinase D, PINK1/Parkin, and myocardin-related transcription factor A so that intervention is directed at correcting pathological overactivation rather than blocking the pathway. Traditional Chinese medicine (TCM) has long been used in ischemic heart disease and is extensively studied as an intervention against MIRI. In addition, active ingredients of Chinese medicinal herbs, TCM compound prescriptions, and electroacupuncture alleviate oxidative stress, maintain calcium ion homeostasis and mitochondrial function, and suppress inflammatory responses and apoptosis, and these effects are accompanied by suppression of excessive RhoA/ROCK activation. However, most of the available studies report only changes in RhoA or ROCK expression, and the evidence establishing RhoA as a necessary target of these interventions remains limited. The clinical trials completed for these interventions used coronary flow and exercise capacity as endpoints without measuring the pathway in patients, and their translation remains to be established. This narrative review summarizes the research on TCM modulation of the RhoA signaling pathway in MIRI and appraises the current state of its clinical translation.