Roles and mechanisms of ginsenoside Rg1 in coronary artery disease: Progress and perspectives

Fig. 1. Mechanisms of the anti-atherosclerotic effects of ginsenoside Rg1. Ginsenoside Rg1 (Rg1) exerts multiple protective effects against atherosclerosis by targeting key cellular components involved in the pathogenesis of the disease. A. Endothelial cells (ECs): Rg1 enhances endothelial function by reducing oxidative stress, promoting the dissociation of the Keap1/Nrf2 complex, and facilitating nuclear translocation of Nrf2. This activation leads to the upregulation of antioxidant enzymes such as SOD and GSH, and increased NO production while reducing ROS and MDA levels. Rg1 also stimulates NO release by increasing ETB receptor expression, facilitating L-arginine transport, and enhancing eNOS phosphorylation. Additionally, Rg1 suppresses the expression of adhesion molecules such as VCAM-1 and ICAM-1, thereby reducing monocyte adhesion and clustering. B. Smooth muscle cells (SMCs): Rg1 inhibits SMC proliferation by modulating the expression of genes through the ERK, PI3K, and PKC pathways, thereby exerting an inhibitory effect on cell proliferation and preventing neointimal hyperplasia. Abbreviations: ETB, endothelin receptor type B; VCAM-1, vascular cell adhesion molecule-1; ICAM-1,…

Fig. 2. Mechanisms of ginsenoside Rg1 in protecting ischemic myocardium. Ginsenoside Rg1 (Rg1) offers significant cardioprotection in ischemic myocardium through multiple mechanisms. A. Anti-apoptotic effects: Rg1 prevents apoptosis in cardiomyocytes by promoting the dissociation of Bcl-2 and Beclin-2, regulating the HIF-α/ERK and PI3K/Akt/mTOR pathways, as well as inhibiting intracellular ATP depletion to suppress AMPK pathway activation. This leads to increased expression of anti-apoptotic proteins Bcl-2 and Beclin-2, and decreased expression of pro-apoptotic proteins Bax, caspase-3, and caspase-9. B. Antioxidant activity: Rg1 enhances oxidative stress response by regulating intracellular Ca2+ equilibrium, reducing ROS, and boosting mitochondrial membrane potential, thus preserving mitochondrial structure and function. Key pathways include inhibition of the RhoA/ROCK pathway, suppression of GSTP-1 to facilitate OPA-1 expression, and activation of the Akt/GSK-3β pathway through P2X7 expression inhibition. C. Anti-inflammatory effects: Rg1 attenuates inflammatory responses in myocardial cells by inhibiting the NF-κB/p65 pathway through TLR4 receptor suppression, stimulating the…

Fig. 3. Mechanisms of ginsenoside Rg1 in modulating myocardial hypertrophy and fibrosis. Ginsenoside Rg1 (Rg1) inhibits myocardial hypertrophy and fibrosis through Various signaling pathways. A. Inhibiting cardiac hypertrophy: Rg1 inhibits cardiac hypertrophy by activating SIRT1/PGC-1α to regulate FFA and energy metabolism in cardiomyocytes, inhibiting the TNF-α/NF-κB and Ca2+/Calpain-1 signaling pathways, and promoting Akt phosphorylation to suppress the MAPK signaling pathway. B. Modulating myocardial fibrosis: Rg1 regulates myocardial fibrosis by activating the SIRT1/PINK1/Parkin pathway, inhibiting the Ca2+/CaN/NFAT3 pathway, promoting MMP2 secretion, and reducing MMP9 secretion. Abbreviations: SIRT1, Sirtuin-1; PGC-1α, PPAR-gamma coactivator 1-alpha; FFA, free fatty acid; NF-κB, nuclear factor kappa B; MAPK, Mitogen-activated protein kinase; PINK1, PTEN-induced kinase 1; CaN, Calcineurin; NFAT3, Nuclear factor of activated T-cells 3.