Irfan Muhammad, Kwon Hyuk-Woo, Lee Dong-Ha, Shin Jung-Hae, Yuk Heung Joo, Kim Dong-Seon, Hong Seung-Bok, Kim Sung-Dae, Rhee Man Hee
Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea.
Department of Biomedical Laboratory Science, Far East University, Eumseong, South Korea.
Front Pharmacol. 2020 May 19;11:698. doi: 10.3389/fphar.2020.00698. eCollection 2020.
The prevalence of cardiovascular diseases (CVDs) is increasing at a high rate, and the available treatment options, sometimes, have complications which necessitates the need to develop safer and efficacious approaches. Ethnomedicinal applications reportedly reduce CVD risk. Jacq. (Ulmaceae) commonly known as Chinese Elm or Lacebark Elm, is native to China, Japan, and Korea. It exhibits anti-inflammatory, antiviral, and anticancer properties, but its anti-platelet properties have not yet been elucidated.
To investigate the pharmacological anti-platelet and anti-thrombotic effects of bark extract.
Human and rat washed platelets were prepared; light transmission aggregometry and scanning electron microscopy was performed to assess platelet aggregation and the change in platelet shape, respectively. Intracellular calcium mobilization, ATP release, and thromboxane-B2 production were also measured. Integrin αβ activation was analyzed in terms of fibrinogen binding, fibronectin adhesion, and clot retraction. The expression of MAPK, Src, and PI3K/Akt pathway proteins was examined. Cyclic nucleotide signaling pathway was evaluated cAMP elevation and VASP phosphorylation. Anti-thrombotic activity of the extract was evaluated using an arteriovenous shunt rat model, whereas its effect on hemostasis in mice was assessed bleeding time assay.
extract significantly inhibited human and rat platelet aggregation in a dose-dependent manner along with inhibition of calcium mobilization, dense granule secretion, and TxB2 production. Integrin αβ mediated inside-out and outside-in signaling events, as evidenced by the inhibition of fibrinogen binding, fibronectin adhesion, and clot retraction. The extract significantly reduced phosphorylation of Src, MAPK (ERK, JNK, and p38), and PI3K/Akt pathway proteins. Cyclic-AMP levels were elevated in treated platelets, while PKAαβγ and VASP phosphorylation was enhanced. reduced thrombus weight in rats and moderately increased bleeding time in mice.
modulates platelet responses and inhibit thrombus formation by regulating integrin αβ mediated inside-out and outside-in signaling events and cAMP signaling pathway.
心血管疾病（CVDs）的患病率正在高速增长，而现有的治疗方案有时会有并发症，这就需要开发更安全有效的治疗方法。据报道，民族药用应用可降低心血管疾病风险。榔榆（榆科），俗称中国榆或蕾丝树皮榆，原产于中国、日本和韩国。它具有抗炎、抗病毒和抗癌特性，但其抗血小板特性尚未阐明。
研究榔榆树皮提取物的药理抗血小板和抗血栓形成作用。
制备人及大鼠洗涤血小板；分别进行光透射聚集测定和扫描电子显微镜检查，以评估血小板聚集和血小板形状变化。还测量了细胞内钙动员、ATP释放和血栓素 - B2生成。从纤维蛋白原结合、纤连蛋白粘附和凝块回缩方面分析整合素αβ激活情况。检测MAPK、Src和PI3K/Akt信号通路蛋白的表达。通过cAMP升高和VASP磷酸化评估环核苷酸信号通路。使用动静脉分流大鼠模型评估提取物的抗血栓活性，而通过出血时间测定评估其对小鼠止血的影响。
提取物以剂量依赖性方式显著抑制人和大鼠血小板聚集，同时抑制钙动员、致密颗粒分泌和TxB2生成。整合素αβ介导的外向内和内向外交联信号事件受到抑制，表现为纤维蛋白原结合、纤连蛋白粘附和凝块回缩受到抑制。提取物显著降低Src、MAPK（ERK、JNK和p38）和PI3K/Akt信号通路蛋白的磷酸化水平。处理后的血小板中环磷酸腺苷水平升高，同时PKAαβγ和VASP磷酸化增强。提取物降低了大鼠的血栓重量，并适度延长了小鼠的出血时间。
榔榆树皮提取物通过调节整合素αβ介导外向内和内向外交联信号事件以及cAMP信号通路来调节血小板反应并抑制血栓形成。
