%0 Journal Article
%T Inhibition of cGAS/STING-Mediated Cellular Senescence Underlies the Protective Effect of Ginsenoside Rg1 in Experimental Pulmonary Hypertension
%A Klara Novak
%A Andrei Benes
%J Pharmaceutical Sciences and Drug Design
%@ 3062-4428
%D 2022
%V 2
%N 1
%R 10.51847/tEoQeHsnVz
%P 101-116
%X Pulmonary hypertension (PH) is a life-threatening disease of the pulmonary vasculature for which effective therapeutic options remain scarce. Although ginsenoside Rg1 has shown beneficial activity in alleviating PH, the molecular basis of its action has not been fully clarified. This work aimed to elucidate the signaling mechanisms through which ginsenoside Rg1 improves PH. A rat model of PH was used to evaluate the therapeutic impact of ginsenoside Rg1 via cardiopulmonary hemodynamic analysis and tissue staining. Network-pharmacology approaches were applied to predict possible molecular targets, and immunofluorescence was used to assess protein expression within the cyclic GMP–AMP synthase (cGAS)/stimulator of interferon genes (STING) axis. Transcriptional and protein levels of senescence indicators were measured using RT-PCR and immunohistochemistry, and ELISA was performed to detect senescence-associated secretory phenotype (SASP) molecules.
Ginsenoside Rg1 markedly reduced right ventricular systolic pressure (RVSP). Echocardiographic analysis showed increased pulmonary artery acceleration time/pulmonary ejection time (PAT/PET) and enhanced tricuspid annular plane systolic excursion (TAPSE), along with a decrease in right ventricular anterior wall thickness (RVAWT). Hematoxylin–eosin staining demonstrated substantial attenuation of pulmonary vascular remodeling. In addition, Rg1 significantly suppressed mRNA and protein levels of senescence markers p21 and p16, and sharply lowered NF-κB, IL-6, and IL-8. These findings support that ginsenoside Rg1 mitigates pulmonary vascular remodeling in PH, potentially through inhibiting cellular senescence via the cGAS/STING pathway.
%U https://galaxypub.co/article/inhibition-of-cgassting-mediated-cellular-senescence-underlies-the-protective-effect-of-ginsenoside-r1jyz1ff81k1hxi