Total flavones from Sceptridium ternatum alleviate pulmonary hypertension through inhibiting the proliferation of vascular endothelial cells

BACKGROUND: Sceptridium ternatum is a traditional Chinese medicine that is prescribed to treat respiratory diseases in China. Our previous study confirmed that total flavones from Sceptridium ternatum (FST) have preventive and therapeutic effects on pulmonary hypertension (PH). The present study sought to investigate the mechanism underpinning the therapeutic efficacy of FST in PH. METHODS: Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays, real-time quantitative PCR (RT-qPCR), western blot, flow cytometry, high-throughput sequencing, and bioinformatics analysis were performed to study the therapeutic mechanism of FST in PH at the gene, cell, and animal levels. RESULTS: The results showed that FST could inhibit the proliferation of both human pulmonary artery smooth muscle cells (HPASMCs) and human pulmonary microvascular endothelial cells (HPMECs), and downregulate the expression of HIF1α and HIF2α, which are the key factors in the pathogenesis and occurrence of PH. FST could also inhibit the activation of the downstream JAK2-STAT3 signaling pathway and upregulate the expression of the negative regulator SOCS1. Vascular endothelial cell and smooth muscle cell proliferation was inhibited and the symptoms of PH were relieved by FST. CONCLUSIONS: The findings of this study offer important clues for the identification of new molecular targets in FST treatment and the development of treatment strategies for PH.