Yin and Yang of ginsenosides: Molecular mechanisms of bidirectional regulation of angiogenesis.

Angiogenesis plays a significant role in the occurrence and development of some difficult-to-treat diseases, including wound healing, cancer, and ischemic diseases. Ginsenosides, the primary active components of Panax ginseng Meyer, exhibit context-dependent bidirectional regulatory effects on angiogenesis, aligning with the Yin-Yang theory in Traditional Chinese Medicine. Generally, PPT-type ginsenosides (e.g., Rg1, F1) promote angiogenesis, whereas PPD-type ginsenosides (e.g., Rb2, Rg3, Rd) inhibit it. Certain ginsenosides, such as Rh2, demonstrate dual pro- and anti-angiogenic activities, the switch of which is determined by dosage, target cell type, and pathological microenvironment. These effects are mediated through modulation of key signaling pathways (e.g., PI3K/Akt, MAPK, JNK) and factors (e.g., VEGF, HIF-1α, MMPs). Based on a literature search using PubMed and Web of Science up to June 2025, this narrative review summarizes the evidence for the bidirectional role of ginsenosides in angiogenesis, explores their molecular mechanisms, and discusses their therapeutic potential in angiogenesis-related diseases, myocardial ischemia, and diabetic retinopathy, providing a foundation for future ginsenoside-based therapies targeting angiogenesis regulation.