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Shionone Exhibits Anti-inflammatory and Antiproliferative Effects in Pulmonary Arterial Endothelial Cells and Smooth Muscle Cells via SIRT1 in Pulmonary Arterial Hypertension

Yunfei Jiang,Bingchang Hei,Wenbo Hao, Shudong Lin,Xuzhi Liu,Xianguo Meng, Yuanyuan Wang,Mingyu Zhao, Haitao Yu, Lei Yang,Zhanjiang Guan

Revista Brasileira de Farmacognosia(2024)

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Abstract
Pulmonary arterial hypertension is a progressive disease characterized by pulmonary artery endothelial cell dysfunction, local inflammation, and abnormal proliferation of pulmonary artery smooth muscle cells. Shionone, derived from the dried roots and rhizomes of Aster tataricus L.f., Asteraceae, exhibits anti-tumor, anti-oxidant, and anti-inflammatory properties. This study aimed to elucidate the roles and molecular mechanisms of shionone in the proliferation of pulmonary artery smooth muscle cells and the function of pulmonary artery endothelial cells in vitro in pulmonary arterial hypertension. The effects of shionone on cell proliferation and apoptosis were investigated in a pulmonary arterial hypertension model of pulmonary artery smooth muscle cells. The impact of shionone on pulmonary artery endothelial cell function was assessed by measuring cell viability, apoptosis, key factors in vascular endothelial function regulation (endothelial nitric oxide synthase, eNOS; endothelin-1, ET-1), and inflammatory factors (tumour necrosis factor alpha, TNF-α; interleukin-1beta, IL-1β; interleukin-6, IL-6). The regulatory role of shionone on sirtuin 1 and the mechanism by which shionone affects pulmonary artery smooth muscle cells proliferation and pulmonary artery endothelial cell function were also explored. Results indicated that shionone inhibited the proliferation and promoted the apoptosis of pulmonary artery smooth muscle cells in a pulmonary artery smooth cell model. Additionally, it enhances pulmonary artery endothelial cell function by increasing cell viability, decreasing apoptosis, and modulating key factors regulating vascular endothelial function and inflammatory factors. The regulatory effect of shionone on sirtuin 1 was also confirmed, with sirtuin 1 participating in the mechanism by which shionone affects pulmonary artery smooth muscle cells proliferation and pulmonary artery endothelial cell function. In conclusion, this study provides new insights into the molecular mechanism of action of shionone as a potential treatment for pulmonary artery smooth, highlighting its ability to inhibit pulmonary artery smooth muscle cells proliferation and restore pulmonary artery endothelial cell function via sirtuin 1 regulation.
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Key words
Chinese Medicinal herb,Pharmacological Therapy,Vascular Remodeling,Cell Model,Small Interfering RNA,Gene Therapy
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