Zhang Ze-Chao, Zhu Min, Huang Shu-Ping, Wei Zhi-Feng, Chen Yu, Shang Chang-Jie
Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Guangxi University of Chinese Medicine, Nanning, 530000, China.
Comb Chem High Throughput Screen. 2025 Jan 2. doi: 10.2174/0113862073336172241220182220.
To investigate the mechanisms through which Qianlong Shutong Formula (QLSTF) exerts its effects on the management of benign prostatic hyperplasia (BPH).
BPH is a prevalent condition among older men and poses significant management challenges due to the limited effectiveness and potential side effects associated with current treatment options. QLSTF, a traditional Chinese medicine, has been utilized in the treatment of BPH; however, its mechanism of action remains inadequately understood.
This study aimed to identify potential therapeutic targets of QLSTF for the management of BPH through the application of network pharmacology and subsequent experimental validation.
QLSTF compounds were identified utilizing liquid chromatography-mass spectrometry (LC-MS). Potential targets of QLSTF, as well as BPH-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro and in vivo experiments were conducted to further verify the findings.
A total of 52 bioactive ingredients of QLSTF and 760 QLSTF-BPH-related targets were screened. Bioinformatics analysis revealed that Afzelin, Ononin, Glycitin, Emodin and Erythritol may be potential candidate agents. AKT1, SRC, STAT3, GRB2, HRAS, MAPK3, PIK3CA, PIK3R1, HSP90AA1, and EP300 could become potential therapeutic targets. PI3KAKT signaling pathway might play an important role in QLSTF against BPH. Moreover, molecular docking suggested that Afzelin, Ononin, Glycitin, Emodin, and Erythritol combined well with AKT1, SRC, STAT3, HRAS, MAPK3, PIK3CA, and PIK3R1, respectively. In vitro and in vivo experiments showed that QLSTF could inhibit the proliferation of cells, as well as the PI3K-Akt signaling pathway, which further confirmed the prediction by network pharmacology strategy and molecular docking.
QLSTF may exert its therapeutic effects on BPH by modulating the PI3K/AKT signaling pathway and inhibiting glandular hyperplasia. This study offers valuable insights into the therapeutic targets of QLSTF in the management of BPH.
探讨前列癃通方（QLSTF）对良性前列腺增生（BPH）治疗作用的机制。
BPH在老年男性中普遍存在，由于目前治疗方法效果有限且存在潜在副作用，给治疗带来了重大挑战。QLSTF作为一种中药，已被用于治疗BPH；然而，其作用机制仍未得到充分了解。
本研究旨在通过网络药理学及后续实验验证，确定QLSTF治疗BPH的潜在治疗靶点。
采用液相色谱-质谱联用（LC-MS）鉴定QLSTF中的化合物。从公共数据库中检索QLSTF的潜在靶点以及与BPH相关的靶点。通过生物信息学分析，包括蛋白质-蛋白质相互作用（PPI）、基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，获取关键生物活性成分、潜在靶点和信号通路。随后，进行分子对接以预测活性化合物与核心靶点的结合。最后，进行体外和体内实验以进一步验证研究结果。
共筛选出QLSTF的52种生物活性成分和760个与QLSTF-BPH相关的靶点。生物信息学分析显示，杨梅苷、芒柄花苷、大豆黄素、大黄素和赤藓糖醇可能是潜在的候选药物。AKT1、SRC、STAT3、GRB2、HRAS、MAPK3、PIK3CA、PIK3R1、HSP90AA1和EP300可能成为潜在的治疗靶点。PI3K-AKT信号通路可能在QLSTF治疗BPH中起重要作用。此外，分子对接表明杨梅苷、芒柄花苷、大豆黄素、大黄素和赤藓糖醇分别与AKT1、SRC、STAT3、HRAS、MAPK3、PIK3CA和PIK3R1结合良好。体外和体内实验表明，QLSTF可抑制细胞增殖以及PI3K-Akt信号通路，进一步证实了网络药理学策略和分子对接的预测结果。
QLSTF可能通过调节PI3K/AKT信号通路和抑制腺体增生对BPH发挥治疗作用。本研究为QLSTF治疗BPH的治疗靶点提供了有价值的见解。
