Exploring the pro-angiogenic potential of Chinese herbal medicines: a comprehensive insight into mechanisms

Pro-angiogenic therapy aims to stimulate the formation of new blood vessels, thereby enhancing blood flow to tissues and organs. Current strategies, such as growth factors, gene therapy, and cell-based approaches, are widely employed to promote angiogenesis. However, these interventions often suffer from off-target effects and limited efficacy due to the complex regulation of angiogenesis. Chinese herbal medicine (CHM) provides a rich source of therapeutic agents and offers promising alternatives for the treatment of vascular insufficiency-related disorders.

This review aims to summarise current research on the pro-angiogenic effects and underlying molecular mechanisms of CHM, including herbal extracts, traditional formulations and key bioactive phytochemicals.

A comprehensive literature search was conducted using electronic databases, including PubMed, Web of Science, and Google Scholar, covering publications from 2003 to 2024. Keywords including "Pro-angiogenic", "Angiogenesis", "Phytochemicals", "Traditional Chinese Medicine", "Natural compounds", "Phytomedicine", "Plant medicine", "Botanical drugs" and "Chinese herbal medicine" were used to retrieve relevant studies. The retrieved articles were then assessed, summarised and synthesized to provide a comprehensive overview of the pro-angiogenic effects of CHMs and the molecular mechanisms underpinning these effects.

We systematically summarised the key molecular mechanisms involved in angiogenesis, including the vascular endothelial growth factor (VEGF), notch signalling, angiopoietin-tie, fibroblast growth factor, platelet-derived growth factor and hypoxia-inducible factor (HIF) pathways. Mechanistically, CHMs exert pro-angiogenic effects through promoting cell survival, proliferation, and migration, primarily through the upregulation of VEGF, Notch signalling, MAPK signalling, HIF-1α, and PI3K- Protein Kinase B (Akt) signalling pathways.

Multiple Chinese herbal extracts, formulations and key phytochemicals demonstrate significant pro-angiogenic effects. The mechanisms of these effects are multifaceted. The evidence highlights the potential of CHMs as promising candidates for pro-angiogenic therapy, warranting the need for further research and development to fully harness their therapeutic value.