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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1530715

Exploring the Multi-Targeted Mechanism of Saikosaponin A in Prostate Cancer Treatment: A Network Pharmacology and Molecular Docking Approach

Provisionally accepted
Genbao Zhu Genbao Zhu 1,2*Zhiming Jiang Zhiming Jiang 2Niuping Zhu Niuping Zhu 1Donghui Wang Donghui Wang 1Tianpeng Guo Tianpeng Guo 1Yiqing Meng Yiqing Meng 1Yi Zhu Yi Zhu 1Kemeng Tan Kemeng Tan 2Mengxue Hu Mengxue Hu 2Heng Tang Heng Tang 2Xuannian Wang Xuannian Wang 1
  • 1 Henan Agricultural University, Zhengzhou, Henan Province, China
  • 2 Wanbei Coal and Power Group General Hospital, Suzhou, Anhui Province, China

The final, formatted version of the article will be published soon.

    Background: Prostate cancer (PCa) is one of the prevalent malignant tumors among men. It can progress to castration-resistant prostate cancer (CRPC), which is significantly more challenging to treat. Saikosaponin A (SSA), a triterpenoid saponin extracted from the genus Bupleurum, exerts numerous pharmacological effects, including anti-inflammatory and anti-tumorigenic effects. However, the mechanism underlying the effects of SSA in prostate cancer treatment remains elusive.In this study, a network pharmacology approach was applied to identify relevant targets from drug-and disease-related databases, and intersections were analyzed using Venny2.1 to construct a Protein-Protein interaction (PPI) interaction network. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to elucidate associated biological functions and signaling pathways. Meanwhile, molecular docking between core targets and SSA was performed using Autodock software. Lastly, in vitro experiments were performed for validation.Results: A least of four key targets, namely BCL2 apoptosis regulator (BCL2), estrogen receptor 1 (ESR1), hypoxia-inducible factor 1 subunit alpha (HIF1A), and signal transducer and activator of transcription 3 (STAT3) were identified in this study, and molecular docking analyses revealed that SSA stably binds to these targets.Moreover, the results of in vitro experiments revealed that SSA significantly inhibited the proliferative and migratory abilities of PC3 cells in a dose-dependent manner.Finally, SSA also induced G1-phase blockade and apoptosis in PC3 cells, further highlighting its potential role in prostate cancer treatment.The present study revealed that SSA exerts anti-tumorigenic effects in prostate cancer by targeting multiple pathways, laying a theoretical reference for its use as a therapeutic candidate for prostate cancer.

    Keywords: Saikosaponin a, prostate cancer, Network Pharmacology, molecular docking, Apoptosis

    Received: 19 Nov 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Zhu, Jiang, Zhu, Wang, Guo, Meng, Zhu, Tan, Hu, Tang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Genbao Zhu, Henan Agricultural University, Zhengzhou, 450002, Henan Province, China

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