The role of HIF-1α in myocardial ischemia protection mechanisms and multi-target rational regulation strategies for natural products

Abstract

Ischaemic heart disease (IHD) remains a major contributor to global morbidity and mortality from cardiovascular disease. Its core mechanism involves an imbalance in myocardial oxygen metabolism, ultimately leading to cardiomyocyte apoptosis or necrosis. As the central regulator of cellular oxygen sensing and adaptation, hypoxia-inducible factor-1α (HIF-1α) plays a pivotal role in the pathogenesis of IHD by orchestrating key pathological processes—such as angiogenesis, inflammation, apoptosis, and mitochondrial dysfunction—through transcriptional regulation of diverse antioxidant and stress-responsive genes. Despite its importance, therapeutic strategies directly targeting HIF-1α remain limited. In contrast, natural products (NPs) possess a long history of clinical application and demonstrated safety, with distinct advantages including multi-target regulation and low toxicity, making them promising candidates for myocardial protection and drug discovery. Accumulating evidence indicate that NPs act through coordinated, multi-target modulation of the HIF-1α signalling network, though their complex mechanisms require further elucidation. This review summarises current insights into the regulatory role of HIF-1α in myocardial ischaemic injury and highlights the therapeutic potential of NPs in modulating this pathway, providing a foundation for novel anti-ischaemic drug development.