Beijing National Laboratory for Molecular Sciences, CAS Research/Education Center for Excellence in Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, National Centre for Mass Spectrometry in Beijing, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
College of Chemical Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Molecules. 2022 Feb 21;27(4):1432. doi: 10.3390/molecules27041432.
Baicalin is a major active ingredient of traditional Chinese medicine , and has been shown to have antiviral, anti-inflammatory, and antitumor activities. However, the protein targets of baicalin have remained unclear. Herein, a chemical proteomics strategy was developed by combining baicalin-functionalized magnetic nanoparticles (BCL-N@MNPs) and quantitative mass spectrometry to identify the target proteins of baicalin. Bioinformatics analysis with the use of Gene Ontology, STRING and Ingenuity Pathway Analysis, was performed to annotate the biological functions and the associated signaling pathways of the baicalin targeting proteins. Fourteen proteins in human embryonic kidney cells were identified to interact with baicalin with various binding affinities. Bioinformatics analysis revealed these proteins are mainly ATP-binding and/or ATPase activity proteins, such as CKB, HSP86, HSP70-1, HSP90, ATPSF1β and ACTG1, and highly associated with the regulation of the role of PKR in interferon induction and the antiviral response signaling pathway ( = 10), PI3K/AKT signaling pathway ( = 10) and eNOS signaling pathway ( = 10). The results show that baicalin exerts multiply pharmacological functions, such as antiviral, anti-inflammatory, antitumor, and antioxidant functions, through regulating the PKR and PI3K/AKT/eNOS signaling pathways by targeting ATP-binding and ATPase activity proteins. These findings provide a fundamental insight into further studies on the mechanism of action of baicalin.
黄芩苷是一种重要的中药活性成分，具有抗病毒、抗炎和抗肿瘤作用。然而，黄芩苷的蛋白质靶标仍不清楚。在此，我们结合黄芩苷功能化磁性纳米颗粒（BCL-N@MNPs）和定量质谱，开发了一种化学蛋白质组学策略，以鉴定黄芩苷的靶蛋白。使用基因本体论、STRING 和 IPA 对黄芩苷靶蛋白进行生物信息学分析，以注释其生物学功能和相关信号通路。在人胚肾细胞中鉴定出 14 种与黄芩苷具有不同结合亲和力的蛋白质。生物信息学分析显示，这些蛋白质主要是 ATP 结合和/或 ATP 酶活性蛋白，如 CKB、HSP86、HSP70-1、HSP90、ATPSF1β 和 ACTG1，与 PKR 在干扰素诱导和抗病毒反应信号通路中的调节作用（=10）、PI3K/AKT 信号通路（=10）和 eNOS 信号通路（=10）高度相关。结果表明，黄芩苷通过靶向 ATP 结合和 ATP 酶活性蛋白，调节 PKR 和 PI3K/AKT/eNOS 信号通路，发挥多种药理作用，如抗病毒、抗炎、抗肿瘤和抗氧化作用。这些发现为进一步研究黄芩苷的作用机制提供了基础。
