AUTHOR=Chen Xing , He Yao , Yu Zhijie , Zuo Jianli , Huang Yan , Ruan Yi , Zheng Xiaoyuan , Ma Yu 

TITLE=Polydatin Glycosides Improve Monocrotaline-Induced Pulmonary Hypertension Injury by Inhibiting Endothelial-To-Mesenchymal Transition

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.862017

DOI=10.3389/fphar.2022.862017

ISSN=1663-9812

ABSTRACT=Objective: To study the effect of polydatin on the injury of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT).
Methods: SD rats were induced to develop PAH injury by a single subcutaneous injection of MCT (60 mg/kg). From the second day, rats in the administration group were orally given sildenafil (20 mg/kg) and polydatin (50 or 100 mg/kg) for 3 weeks. At the end of the experiment, right ventricular hypertrophy (RVH) index of SD rats was calculated, pathological damage was assessed by HE staining, transcription levels of target genes were detected by RT-PCR and Elisa, and expression levels of EndMT (EMT) related proteins were detected by immunohistochemistry (IHC) and immunofluorescence (IF). Finally, molecular docking analysis was used to verify the interaction of polydatin on the main targets.
Results: Polydatin (30,60 mg/kg) could significantly restore the body function, reduce McT-induced PAH injury, reduce serum biochemical indices, inhibit EMT process, maintain the integrity of pulmonary endothelial barrier and alleviate pulmonary vascular remodeling in SD rats. The interaction between polydatin and EMT target was confirmed by molecular docking operation.
Conclusion: Pharmacological experiments combined with Combining molecular docking was first used to clarify that polydatin can reduce the pulmonary endothelial dysfunction and pulmonary vascular remodeling induced by MCT by inhibiting EMT. The results of the study provide new ideas for the further treatment of PAH injury.