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运用网络药理学和实验验证探索锯叶棕及其核心成分治疗良性前列腺增生症的药理机制。

Network pharmacology and experimental validation to explore the pharmacological mechanism of saw palmetto and its core ingredients in benign prostatic hyperplasia treatment.

作者信息

Zhang Bo, Wang Yiying, Yan Kunping, Yang Jiangang

机构信息

Research and Development Center, Shaanxi Prispex SFE Co., Ltd., Xi'an, 710061, Shaanxi, China.

School of Public Health, Hebei Medical University, Shijiazhuang, 050000, Hebei, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):543-555. doi: 10.1007/s00210-024-03289-z. Epub 2024 Jul 17.

DOI:10.1007/s00210-024-03289-z
PMID:39017714
Abstract

Benign prostatic hyperplasia (BPH) is a prevalent urological condition that predominantly affects the geriatric male population, resulting in lower urinary tract symptoms. Saw palmetto is a traditional Chinese medicine for treating BPH. This study aimed to investigate the potential therapeutic mechanisms of saw palmetto in BPH treatment. The active ingredients and potential targets of saw palmetto were obtained through the TCMSP database. BPH-related targets were retrieved from the GeneCards database. PPI, GO, and KEEG analyses were performed to predict the potential therapeutic mechanism. The active ingredient-common target and common target-pathway networks were constructed by Cytoscape software. Molecular docking and cellular experiments were carried out to further validate the potential mechanism. We obtained 13 active components in saw palmetto and 56 common targets in BPH treatment. KEEG analysis showed that the estrogen signaling pathway was the most enriched and exhibited a close association with BPH. PPI analysis, along with ingredient-target and target-pathway network analyses, indicated that stigmasterol was the core ingredient and PGR, NCOA1, and NCOA2 were identified as the hub genes mediating the effects of saw palmetto against BPH. In addition, molecular docking showed that stigmasterol had strong binding to PGR, NCOA1, and NCOA2. Cellular experiments revealed that stigmasterol significantly increased the percentage of BPH-1 cells in the G0/G1 phase and inhibited cell viability and division. Furthermore, it notably reduced the expression of PGR, NCOA1, and NCOA2. Saw palmetto might inhibit cell viability and division by suppressing the expression of PGR, NCOA1, and NCOA2, thereby playing a therapeutic role in treating BPH.

摘要

良性前列腺增生(BPH)是一种常见的泌尿系统疾病,主要影响老年男性人群,导致下尿路症状。锯叶棕是一种治疗BPH的传统中药。本研究旨在探讨锯叶棕治疗BPH的潜在治疗机制。通过中药系统药理学数据库(TCMSP)获得锯叶棕的活性成分和潜在靶点。从基因卡片数据库检索BPH相关靶点。进行蛋白质-蛋白质相互作用(PPI)、基因本体(GO)和京都基因与基因组百科全书(KEGG)分析以预测潜在的治疗机制。利用Cytoscape软件构建活性成分-共同靶点和共同靶点-通路网络。进行分子对接和细胞实验以进一步验证潜在机制。我们在锯叶棕中获得了13种活性成分和BPH治疗中的56个共同靶点。KEGG分析表明雌激素信号通路最富集,且与BPH密切相关。PPI分析以及成分-靶点和靶点-通路网络分析表明,豆甾醇是核心成分,孕酮受体(PGR)、核受体辅激活因子1(NCOA1)和核受体辅激活因子2(NCOA2)被确定为介导锯叶棕抗BPH作用的枢纽基因。此外,分子对接表明豆甾醇与PGR、NCOA1和NCOA2有很强的结合力。细胞实验表明,豆甾醇显著增加了BPH-1细胞在G0/G1期的比例,抑制了细胞活力和分裂。此外,它显著降低了PGR、NCOA1和NCOA2的表达。锯叶棕可能通过抑制PGR、NCOA1和NCOA2的表达来抑制细胞活力和分裂,从而在治疗BPH中发挥治疗作用。

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