Zhang Yi, Zhao Lu, Wang Liping, Yue Ruixue, Zhu Hong, Zhang Wenting, Sun Jian, Zhang Zifeng, Ma Daifu
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China.
Xuzhou Institute of Agricultural Sciences in Jiangsu Xuhuai District, Xuzhou, China.
Front Pharmacol. 2024 Aug 21;15:1414739. doi: 10.3389/fphar.2024.1414739. eCollection 2024.
Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by antiplatelet autoantibodies, thrombocytopenia, and bleeding, however, its treatment options are limited. In this study, a kind of active component, chlorogenic acid compounds (CGAs) from sweetpotato leaves was extracted out to explore its medicinal value and provide novel therapeutic strategies for the treatment of ITP. CGAs was isolated by ionic liquids-ultrasound (IL-UAE), which contains six isomers of chlorogenic acid with total purity of 95.69%. The thrombopoietic effect and mechanism of CGAs were investigated using prediction and experimental validation. The changes of HEL cells morphology in volume and the increase in the total cell percentage of polyploid cells indicated that CGAs could promote megakaryocyte differentiation. Meanwhile, CGAs could promote platelet formation in a murine model of ITP, which was established by injection of antiplatelet antibody. Further quantitative proteomics analysis and Western blot verification revealed that CGAs could activate PI3K/AKT signaling pathway, which confirmed the mechanism prediction. It suggested that CGAs may provide a novel therapeutic strategy that relies on the PI3K/AKT pathway to facilitate megakaryocyte differentiation and platelet production.
特发性血小板减少性紫癜(ITP)是一种自身免疫性疾病,其特征为抗血小板自身抗体、血小板减少和出血,然而其治疗选择有限。在本研究中,从红薯叶中提取出一种活性成分绿原酸类化合物(CGAs),以探索其药用价值,并为ITP的治疗提供新的治疗策略。通过离子液体-超声(IL-UAE)分离出CGAs,其含有六种绿原酸异构体,总纯度为95.69%。利用预测和实验验证研究了CGAs的促血小板生成作用及其机制。HEL细胞体积形态的变化以及多倍体细胞总细胞百分比的增加表明CGAs可促进巨核细胞分化。同时,CGAs可促进通过注射抗血小板抗体建立的ITP小鼠模型中的血小板生成。进一步的定量蛋白质组学分析和蛋白质印迹验证表明,CGAs可激活PI3K/AKT信号通路,这证实了机制预测。这表明CGAs可能提供一种依赖PI3K/AKT途径促进巨核细胞分化和血小板生成的新治疗策略。