Ginsenoside Rg1 Prevents and Treats Acute Pulmonary Injury Induced by High-Altitude Hypoxia

This study aimed to investigate the protective effects of ginsenoside Rg1 on high-altitude hypoxia-induced acute lung injury (ALI) and elucidated its molecular targets and related pathways, specifically its association with the fluid shear stress pathway. Using a combination of bioinformatics analysis and both in vivo and in vitro experiments, we assessed the role of ginsenoside Rg1 in mitigating physiological and biochemical disturbances induced by hypoxia. In the in vivo experiments, we measured arterial blood gas parameters, levels of inflammatory cells and cytokines, erythrocyte and platelet parameters, and conducted histological analysis in rats. The in vitro experiments utilized human pulmonary microvascular endothelial cells (HPMECs) and A549 cells to examine cell viability, intracellular reactive oxygen species (ROS) and Ca²⁺ levels, and mitochondrial function. The results of the in vivo experiments demonstrate that ginsenoside Rg1 significantly increased arterial blood oxygen partial pressure and saturation, elevated arterial blood glucose levels, and stabilized respiratory and metabolic functions in rats. It also reduced inflammatory cells and cytokines, such as tumor necrosis factor-α and interleukin-6, and improved erythrocyte and platelet abnormalities, supporting its protective role through the regulation of the fluid shear stress pathway. Histological and ultrastructural analyses revealed that Rg1 significantly protected lung tissue structure and organelles. In vitro experiments further confirmed that Rg1 improved cell viability in HPMEC and A549 cells under hypoxic conditions, decreased intracellular ROS and Ca²⁺ levels, and enhanced mitochondrial function. These findings collectively demonstrate that ginsenoside Rg1 exerts significant protective effects against high-altitude hypoxia-induced ALI by enhancing oxygen delivery and utilization, reducing inflammatory responses, and maintaining cellular metabolism and vascular function. Notably, the protective effects of Rg1 are closely associated with the regulation of the fluid shear stress pathway, suggesting its potential for treating high-altitude hypoxia-related diseases.