黄芩素是中药黄芩中最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）的确切药理学机制仍不清楚。本研究旨在通过网络药理学和实验相结合的方法阐明黄芩素抗CRPC的潜在机制，从而为CRPC治疗研究提供新途径。利用TCMSP数据库获得黄芩素的药理和分子特性。黄芩素相关靶标从多个来源收集，包括 SwissTargetPrediction、PharmMapper 和 CTD。与CRPC相关的目标是从DisGeNET、GeneCards和CTD获得的。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GO和KEGG通路富集分析。通过细胞实验验证了靶点的有效性，共获得了黄芩素治疗CRPC的131个潜在靶点。其中TP53、AKT1、ALB、CASP3、HSP90AA1等被Cytoscape 3.7.2认定为核心靶点。 GO功能富集分析产生了926个条目，其中包括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、前列腺癌中的Pathways、糖尿病并发症中的AGE-RAGE信号通路、TP53信号通路、PI3K-Akt信号通路等。细胞实验证实黄芩素可能抑制CRPC 细胞增殖并诱导细胞周期停滞在 G1 期。这种效应可能与 TP53/CDK2/cyclin E1 通路有关。此外，CETSA的结果提示黄芩素可能直接与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，这些研究结果为新型抗CRPC药物的研发提供了宝贵的见解。版权所有©2024窦，崔，周，付，周，张，张和张。

Baicalein, one of the most abundant flavonoids found in Chinese herb Scutellaria baicalensis 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.Copyright © 2024 Dou, Cui, Zhou, Fu, Zhou, Zhang, Zhang and Zhang.