Dou Baokai, Cui Yingjie, Zhou Qianqian, Fu Jiawei, Zhou Yi, Zhang Xiwu, Zhang Qi, Zhang Jing
Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Shandong University School of Basic Medical Sciences, Jinan, Shandong, China.
Front Pharmacol. 2024 Jun 26;15:1397703. doi: 10.3389/fphar.2024.1397703. eCollection 2024.
Baicalein, one of the most abundant flavonoids found in Chinese herb Georgi, exhibits pharmacological activities against various cancers. However, the precise pharmacological mechanism of baicalein in treating castration-resistant prostate cancer (CRPC) remains elusive. This study aimed to elucidate the potential mechanism of baicalein against CRPC through a combination of network pharmacology and experimental approaches, thereby providing new avenues for research in CRPC treatment.
The pharmacological and molecular properties of baicalein were obtained using the TCMSP database. Baicalein-related targets were collected from multiple sources including SwissTargetPrediction, PharmMapper and CTD. Targets related to CRPC were acquired from DisGeNET, GeneCards, and CTD. The protein-protein interaction (PPI) was analyzed using STRING 11.5, and Cytoscape 3.7.2 software was utilized to explore the core targets of baicalein on CRPC. GO and KEGG pathway enrichment analysis were performed using DAVID database. Cell experiments were carried out to confirm the validity of the targets.
A total of 131 potential targets of baicalein for the treatment of CRPC were obtained. Among them, TP53, AKT1, ALB, CASP3, and HSP90AA1, etc., were recognized as core targets by Cytoscape 3.7.2. GO function enrichment analysis yielded 926 entries, including 703 biological process (BP) terms, 84 cellular component (CC) terms and 139 molecular function (MF) terms. The KEGG pathway enrichment analysis unveiled 159 signaling pathways, mainly involved in Pathways in cancer, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, TP53 signaling pathway, and PI3K-Akt signaling pathway, etc. Cell experiments confirmed that baicalein may inhibit the proliferation of CRPC cells and induce cell cycle arrest in the G1 phase. This effect could be associated with the TP53/CDK2/cyclin E1 pathway. In addition, the results of CETSA suggest that baicalein may directly bind to TP53.
Based on network pharmacology analysis and cell experiments, we have predicted and validated the potential targets and related pathways of baicalein for CRPC treatment. This comprehensive approach provides a scientific basis for elucidating the molecular mechanism underlying the action of baicalein in CRPC treatment. Furthermore, these findings offer valuable insights and serve as a reference for the research and development of novel anti-CRPC drugs.
黄芩素是中药黄芩中含量最为丰富的黄酮类化合物之一，具有抗多种癌症的药理活性。然而，黄芩素治疗去势抵抗性前列腺癌（CRPC）的确切药理机制仍不清楚。本研究旨在通过网络药理学和实验方法相结合的方式阐明黄芩素抗CRPC的潜在机制，从而为CRPC治疗研究提供新途径。
利用中药系统药理学数据库与分析平台（TCMSP）获取黄芩素的药理和分子特性。从包括瑞士靶点预测、药靶映射器和CTD等多个来源收集与黄芩素相关的靶点。从疾病基因数据库（DisGeNET）、基因卡片（GeneCards）和CTD获取与CRPC相关的靶点。使用STRING 11.5分析蛋白质-蛋白质相互作用（PPI），并利用Cytoscape 3.7.2软件探索黄芩素对CRPC的核心靶点。使用DAVID数据库进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。进行细胞实验以确认靶点的有效性。
共获得131个黄芩素治疗CRPC的潜在靶点。其中，TP53、AKT1、ALB、CASP3和HSP90AA1等被Cytoscape 3.7.2识别为核心靶点。GO功能富集分析产生926个条目，包括703个生物过程（BP）术语、84个细胞成分（CC）术语和139个分子功能（MF）术语。KEGG通路富集分析揭示了159条信号通路，主要涉及癌症通路、前列腺癌、糖尿病并发症中的晚期糖基化终末产物受体（AGE-RAGE）信号通路、TP53信号通路和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K-Akt）信号通路等。细胞实验证实黄芩素可能抑制CRPC细胞的增殖并诱导细胞周期停滞于G1期。这种作用可能与TP53/细胞周期蛋白依赖性激酶2（CDK2）/细胞周期蛋白E1通路有关。此外，热蛋白质组分析（CETSA）结果表明黄芩素可能直接与TP53结合。
基于网络药理学分析和细胞实验，我们预测并验证了黄芩素治疗CRPC的潜在靶点和相关通路。这种综合方法为阐明黄芩素在CRPC治疗中作用的分子机制提供了科学依据。此外，这些发现提供了有价值的见解，并为新型抗CRPC药物的研发提供参考。
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