Ding Rongzhen, Xie Haiping, Zhang Yu, Qin Li, Peng Guoran, Yi Jian, Tan Junlan, Cao Xianya, Zheng Runxiu, Dai Aiguo
Department of Health Management, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410021, People's Republic of China.
Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People's Republic of China.
Drug Des Devel Ther. 2025 Jul 29;19:6487-6504. doi: 10.2147/DDDT.S527938. eCollection 2025.
Pulmonary hypertension (PH) is a fatal pulmonary vascular disease that currently lacks effective treatment methods. Ginsenoside Rg1 has positive effects on improving PH, but its specific mechanism remains unclear.
This study was designed to investigate the molecular mechanisms of ginsenoside Rg1 in improving PH.
The therapeutic efficacy of ginsenoside Rg1 in PH rat model was assessed using cardiopulmonary hemodynamic measurements and histopathological staining. Network pharmacology analysis was used to predict potential targets, and the expression of cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway proteins was evaluated by immunofluorescence staining. Senescence marker gene transcription and protein levels were assessed by RT-PCR and immunohistochemistry, respectively. Finally, ELISA was employed to quantify senescence-associated secreted proteins (SASP).
Our results demonstrate that ginsenoside Rg1 significantly reduces right ventricular systolic pressure (RVSP). Ultrasound findings indicate that ginsenoside Rg1 increases the pulmonary artery acceleration time to pulmonary ejection time ratio (PAT/PET) and tricuspid annular plane systolic excursion (TAPSE), while reducing the right ventricular anterior wall thickness (RVAWT). Histological examination (HE) suggests that ginsenoside Rg1 significantly diminishes pulmonary vascular remodeling. Furthermore, ginsenoside Rg1 markedly decreases the mRNA and protein expression of the aging markers p21 and p16, as well as significantly reduces the NF-kB, IL-6, and IL-8.
This study presents compelling evidence that ginsenoside Rg1 may enhance pulmonary vascular remodeling in PH by inhibiting cell senescence via the cGAS/STING signaling pathway.
肺动脉高压（PH）是一种致命的肺血管疾病，目前缺乏有效的治疗方法。人参皂苷Rg1对改善PH有积极作用，但其具体机制尚不清楚。
本研究旨在探讨人参皂苷Rg1改善PH的分子机制。
采用心肺血流动力学测量和组织病理学染色评估人参皂苷Rg1在PH大鼠模型中的治疗效果。利用网络药理学分析预测潜在靶点，并通过免疫荧光染色评估环鸟苷酸-腺苷酸合成酶（cGAS）/干扰素基因刺激因子（STING）信号通路蛋白的表达。分别通过RT-PCR和免疫组织化学评估衰老标记基因的转录和蛋白水平。最后，采用ELISA法对衰老相关分泌蛋白（SASP）进行定量分析。
我们的结果表明，人参皂苷Rg1可显著降低右心室收缩压（RVSP）。超声检查结果显示，人参皂苷Rg1可提高肺动脉加速时间与射血时间比值（PAT/PET）和三尖瓣环平面收缩期位移（TAPSE），同时降低右心室前壁厚度（RVAWT）。组织学检查（HE）表明，人参皂苷Rg1可显著减轻肺血管重塑。此外，人参皂苷Rg1可显著降低衰老标志物p21和p16的mRNA和蛋白表达，并显著降低NF-κB、IL-6和IL-8水平。
本研究提供了有力证据，表明人参皂苷Rg1可能通过cGAS/STING信号通路抑制细胞衰老，从而改善PH中的肺血管重塑。
