Phytomedicine ( IF 6.7 ) Pub Date : 2021-09-20 , DOI: 10.1016/j.phymed.2021.153767 Ziqi Lu 1 , Yuxin Ye 2 , Youchen Liu 2 , Xinrong Yang 2 , Qi Ding 2 , Yiting Wang 2 , Zhongrui Wu 2 , Yaxian Zhan 2 , Shuhua Gui 2 , Bingqing Lin 3 , Baoqin Lin 2
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Background
Deep vein thrombosis (DVT) is a kind of blood stasis syndrome. Paeoniae Radix Rubra (PRR) has long been widely used for eliminating blood stasis in China, but its effect on DVT has not yet been reported.
Purpose
The present study aimed to assess the potential inhibitory effect of the aqueous extract of PRR (i.e.,PRR dispensing granule, PRRDG) on DVT and explore the underlying mechanism.
Study design/Methods
The chemical profile of PRRDG was analyzed by high-performance liquid chromatography. Sprague-Dawley rats were intragastrically treated with PRRDG (0.625, 1.25 and 1.875 g crude drug/kg/d) once daily for 7 consecutive days. On the sixth day, a model of inferior vena cava (IVC) stenosis-induced DVT was established. All rats were sacrificed on the seventh day. Serum was collected for enzyme-linked immunosorbent assay. Thrombus-containing IVC was weighed and further processed for histopathologic examination, immunohistochemical analysis and western blotting. LiCl and LY294002 were adopted to block and increase the activity of glycogen synthase kinase 3β (GSK3β), respectively.
Results
The chemical profile analysis showed that paeoniflorin, benzoylpaeoniflorin, albiflorin, gallic acid and catechin were the main constituents of PRRDG. LiCl decreased thrombus weight, reduced the number of inflammatory cells in thrombus and vein wall, down-regulated phosphorylated NF-κB p65 (p-p65) protein expression. Similarly, PRRDG decreased thrombus weight and tissue factor (TF) protein expression. PRRDG reduced the protein expression levels of P-selectin, monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in venous endothelium, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the number of inflammatory cells in thrombus and vein wall. Moreover, PRRDG down-regulated p-p65 protein expression and up-regulated phosphorylated GSK3β (p-GSK3β) protein expression. LY294002 abrogated the inhibitory effects of PRRDG on thrombus weight, TF protein expression, TNF-α and IL-1β serum levels, inflammatory cells influxes, and p-p65 protein expression.
Conclusion
PRRDG prevents DVT by ameliorating inflammation through inhibiting GSK3β activity.
中文翻译：
赤芍水提物通过抑制 GSK3β 活性改善炎症，预防深静脉血栓形成
背景
深静脉血栓形成（DVT）是一种血瘀证。赤芍(PRR)长期以来在我国被广泛用于化瘀，但其对深静脉血栓形成的作用尚未见报道。
目的
本研究旨在评估 PRR 的水提物（即PRR 分配颗粒，PRRDG）对 DVT的潜在抑制作用并探讨其潜在机制。
研究设计/方法
PRRDG 的化学特征通过高效液相色谱分析。Sprague-Dawley 大鼠连续 7 天每天一次用 PRRDG（0.625、1.25 和 1.875 g 生药/kg/d）灌胃治疗。第六天建立下腔静脉（IVC）狭窄致深静脉血栓形成模型。在第七天处死所有大鼠。收集血清用于酶联免疫吸附测定。对含血栓的 IVC 称重并进一步处理以进行组织病理学检查、免疫组织化学分析和蛋白质印迹。LiCl 和 LY294002 分别用于阻断和增加糖原合酶激酶 3β (GSK3β) 的活性。
结果
化学谱分析表明，芍药苷、苯甲酰芍药苷、白花苷、没食子酸和儿茶素是PRRDG的主要成分。LiCl 降低血栓重量，减少血栓和静脉壁中炎症细胞的数量，下调磷酸化 NF-κB p65 (p-p65) 蛋白表达。同样，PRRDG 降低血栓重量和组织因子 (TF) 蛋白表达。PRRDG 降低了静脉内皮、血清中 P-选择素、单核细胞趋化蛋白-1 (MCP-1)、细胞间细胞粘附分子-1 (ICAM-1) 和血管细胞粘附分子-1 (VCAM-1) 的蛋白表达水平肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的水平，以及血栓和静脉壁中炎症细胞的数量。而且，PRRDG 下调 p-p65 蛋白表达并上调磷酸化 GSK3β (p-GSK3β) 蛋白表达。LY294002 消除了 PRRDG 对血栓重量、TF 蛋白表达、TNF-α 和 IL-1β 血清水平、炎症细胞流入和 p-p65 蛋白表达的抑制作用。
结论
PRRDG 通过抑制 GSK3β 活性改善炎症来预防 DVT。
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