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Preventive treatment with ginsenoside Rb1 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats and involves store-operated calcium entry inhibition
Pharmaceutical Biology ( IF 3.8 ) Pub Date : 2020-01-01 , DOI: 10.1080/13880209.2020.1831026
Rui-Xing Wang 1, 2 , Rui-Lan He 1, 2 , Hai-Xia Jiao 1, 2 , Run-Tian Zhang 1 , Jing-Yi Guo 1, 2 , Xiao-Ru Liu 1, 3 , Long-Xin Gui 1, 2 , Mo-Jun Lin 1, 2 , Zhi-Juan Wu 1, 2
Affiliation  

Abstract Context Ginsenoside Rb1, the main active ingredient of ginseng, exhibits ex vivo depression of store-operated calcium entry (SOCE) and related vasoconstriction in pulmonary arteries derived from pulmonary hypertension (PH) rats. However, the in vivo effects of ginsenoside Rb1 on PH remain unclear. Objective This study explored the possibility of using ginsenoside Rb1 as an in vivo preventive medication for type I PH, i.e., pulmonary arterial hypertension (PAH), and potential mechanisms involving SOCE. Materials and methods Male Sprague-Dawley rats (170–180 g) were randomly divided into Control, MCT, and MCT + Rb1 groups (n = 20). Control rats received only saline injection. Rats in the MCT + Rb1 and MCT groups were intraperitoneally administered single doses of 50 mg/kg monocrotaline (MCT) combined with 30 mg/kg/day ginsenoside Rb1 or equivalent volumes of saline for 21 consecutive days. Subsequently, comprehensive parameters related to SOCE, vascular tone, histological changes and hemodynamics were measured. Results Ginsenoside Rb1 reduced MCT-induced STIM1, TRPC1, and TRPC4 expression by 35.00, 31.96, and 32.24%, respectively, at the protein level. SOCE-related calcium entry and pulmonary artery contraction decreased by 162.6 nM and 71.72%. The mean pulmonary artery pressure, right ventricle systolic pressure, and right ventricular mass index decreased by 19.5 mmHg, 21.6 mmHg, and 39.50%. The wall thickness/radius ratios decreased by 14.67 and 17.65%, and the lumen area/total area ratios increased by 18.55 and 15.60% in intrapulmonary vessels with 51–100 and 101–150 μm o.d. Conclusion Ginsenoside Rb1, a promising candidate for PH prevention, inhibited SOCE and related pulmonary vasoconstriction, and relieved MCT-induced PAH in rats.

中文翻译:

人参皂苷 Rb1 的预防性治疗可改善野百合碱诱导的大鼠肺动脉高压,并涉及钙库操作的钙进入抑制

摘要背景人参的主要活性成分人参皂苷 Rb1 表现出体外抑制钙离子进入 (SOCE) 和相关的肺动脉高压 (PH) 大鼠肺动脉收缩。然而,人参皂苷 Rb1 对 PH 的体内影响仍不清楚。目的 本研究探讨使用人参皂苷 Rb1 作为 I 型 PH,即肺动脉高压 (PAH) 的体内预防药物的可能性,以及涉及 SOCE 的潜在机制。材料和方法 雄性 Sprague-Dawley 大鼠(170–180 g)随机分为 Control、MCT 和 MCT + Rb1 组(n = 20)。对照大鼠仅接受盐水注射。MCT + Rb1 和 MCT 组的大鼠连续 21 天腹腔注射单剂量 50 mg/kg 野百合碱 (MCT) 和 30 mg/kg/天人参皂苷 Rb1 或等量体积的盐水。随后,测量了与 SOCE、血管张力、组织学变化和血流动力学相关的综合参数。结果 Ginsenoside Rb1 在蛋白质水平上使 MCT 诱导的 STIM1、TRPC1 和 TRPC4 表达分别降低了 35.00、31.96 和 32.24%。SOCE 相关的钙进入和肺动脉收缩减少了 162.6 nM 和 71.72%。平均肺动脉压、右心室收缩压和右心室质量指数分别下降 19.5 mmHg、21.6 mmHg 和 39.50%。壁厚/半径比分别下降了 14.67 和 17.65%,管腔面积/总面积比分别增加了 18.55 和 15。
更新日期:2020-01-01
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