Department of Medicinal Chemistry and Natural Medicine Chemistry, Department of Pharmacognosy, College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, 150081, China.
Sci Rep. 2018 Apr 3;8(1):5556. doi: 10.1038/s41598-018-23775-8.
Pulmonary arterial hypertension (PAH) is a progressive cardiovascular-disease with high mortality lacking high-efficiency drug. Our efforts attempted to delineate therapeutic action of osthole produced by Angelica Pubescens Maxim, which has the capacity to treat PAH by exploiting an iTRAQ-based proteomic method. Excitingly, osthole was observed to significantly restore 98 of 315 differential proteins significantly modified by PAH progression. They were primarily annotated into 24 signaling pathways. Four mostly affected proteins (RPL15, Cathepsin S, Histone H3.3 and HMGB1) were experimentially validated which belonged to ribosome pathway, oxidative phosphorylation pathway, systemic lupus erythematosus pathway, complement and coagulation cascades pathway, whose modifications and modulations mostly accounted for therapeutic capacity of this compound against PAH. Altogether, our findings demonstrated that global proteomics is a promising systems-biology approach for deciphering therapeutic actions and associated mechanisms of natural products derived from traditional Chinese medicine. Importantly, osthole is supposed to be a candidate compound for new drug development to treat PAH.
肺高血压（PAH）是一种进展性心血管疾病，死亡率高，缺乏高效药物。我们努力描绘当归素（Angelica Pubescens Maxim）产生的治疗作用，该物质通过 iTRAQ 蛋白质组学方法治疗 PAH。令人兴奋的是，当归素显著恢复了 315 个由 PAH 进展显著改变的差异蛋白中的 98 个。它们主要被注释为 24 个信号通路。四个受影响最大的蛋白质（RPL15、组织蛋白酶 S、组蛋白 H3.3 和高迁移率族蛋白 1）通过实验验证，它们属于核糖体途径、氧化磷酸化途径、系统性红斑狼疮途径、补体和凝血级联途径，这些修饰和调节主要解释了该化合物治疗 PAH 的能力。总之，我们的发现表明，整体蛋白质组学是一种有前途的系统生物学方法，可用于破译源自中药的天然产物的治疗作用和相关机制。重要的是，当归素可能是治疗 PAH 的新药开发的候选化合物。
