多西他赛（DTX）耐药降低前列腺癌（PCa）的治疗效果。越来越多的报告支持植物化学物质在逆转DTX耐药性方面的作用。本研究旨在确定淫羊藿和莪朮提取物（ECe），特别是淫羊藿苦杏酮，是否减轻DTX耐药性并探索其潜在机制。利用网络药理学预测ECe活性成分与PCa之间的调节通路。基于对DTX敏感的LNCaP细胞建立了DTX耐药细胞系LNCaP/R，并进一步建立了异种移植模型。通过HLPC-MS确定ECe中的活性成分。通过分子对接分析淫羊藿苦杏酮与靶点的结合。应用生化实验确定淫羊藿苦杏酮调节DTX敏感性的可能机制。预测Akt1和PI3K-Akt信号通路是药物与PCa之间的主要功能靶点。ECe和DTX抑制了移植瘤生长、炎症、细胞活力并促进了细胞凋亡。在ECe中检测到淫羊藿和苦杏酮，并且淫羊藿和苦杏酮与Akt1进行了对接。此外，ECe、淫羊藿苦杏酮和DTX下调了AR、PSA、PI3K、Akt1、mTOR和HIF-1ɑ。此外，ECe、淫羊藿苦杏酮和DTX增加了葡萄糖和PDH，降低了乳酸、ATP和LDH，并下调了c-Myc、hnRNPs、VEGF、PFK1和PKM2。值得注意的是，与ECe或淫羊藿苦杏酮相比，DTX的抗PCa效果在LNCaP/R模型中有所减弱。淫羊藿苦杏酮和DTX的联合效果优于DTX。我们的数据支持淫羊藿苦杏酮通过抑制PI3K-Akt信号通路和Warburg效应逆转DTX耐药性，为改进PCa的治疗措施提供了新思路。© 2023年。Springer Nature旗下BioMed Central有限公司。

Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms.Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity.Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX.Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.© 2023. BioMed Central Ltd., part of Springer Nature.