Effect and Mechanism of Aloin in Ameliorating Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Network Pharmacology and Experimental Verification.

IF 5.1 2区医学 Q1 CHEMISTRY, MEDICINAL Drug Design, Development and Therapy Pub Date : 2025-03-14 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S473678

Rongxin Li, Yanan Wang, Yongfeng Lao, Chengyu You, Liangliang Qing, Xin Guan, Jian Wang, Xiaolong Li, Qingchao Li, Shuai Liu, Zhilong Dong

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Abstract

Purpose: This research aims to investigate the role and potential mechanisms of Aloin in Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) through network pharmacology and experimental approaches.

Methods: Using network pharmacology methods, potential targets of Aloin and targets related to CP/CPPS were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against CP/CPPS. The effects of Aloin in ameliorating CP/CPPS were verified in animal experiments.

Results: A total of 235 genes interacting with Aloin in CP/CPPS were identified. PPI network analysis revealed five core targets: AKT1, EGFR, ESR1, HSP90AA1, and SRC. GO analysis yielded 2916 enrichment results, with 2562 related to Biological Process (BP), 94 to Cellular Component (CC), and 260 to Molecular Function (MF). KEGG pathway analysis identified 172 pathways. Molecular docking confirmed stable binding between Aloin and core targets. Molecular dynamics simulations further validated binding stability by analyzing Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg), hydrogen bonds, Solvent Accessible Surface Area (SASA), and Gibbs free energy of Aloin-target complexes. Experimental validation showed that Aloin alleviated pain, reduced inflammatory factors, and decreased oxidative stress in a rat model of CP/CPPS. The qRT-PCR results showed that Aloin intervention reduced the mRNA expression of AKT1, EGFR, HSP90AA1, and SRC, while increasing ESR1 mRNA expression. These changes may underlie its therapeutic effects in CP/CPPS.

Conclusion: Our study revealed that Aloin exerts a beneficial effect on mitigating the pain symptoms associated with CP/CPPS, ameliorating inflammation, and reducing oxidative stress. Through network pharmacology, potential targets and signaling pathways were identified, suggesting the therapeutic promise of Aloin for CP/CPPS. These findings advocate for further exploration into its clinical efficacy and mechanistic underpinnings in the treatment of CP/CPPS.

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芦荟素改善慢性前列腺炎/慢性盆腔疼痛综合征的作用及机制：网络药理学及实验验证。

目的：本研究旨在通过网络药理学和实验方法探讨芦荟素在慢性前列腺炎/慢性盆腔疼痛综合征（CP/CPPS）中的作用及其可能机制。方法：采用网络药理学方法，从公开数据库中筛选芦荟素的潜在靶点和与CP/CPPS相关的靶点。通过蛋白-蛋白相互作用（PPI）网络、基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，预测芦荟素抗CP/CPPS的核心靶点和通路。动物实验验证了芦荟素改善CP/CPPS的作用。结果：在CP/CPPS中共鉴定出235个与芦荟素相互作用的基因。PPI网络分析揭示了5个核心靶点：AKT1、EGFR、ESR1、HSP90AA1和SRC。氧化石墨烯分析得到2916个富集结果，其中2562个与生物过程（BP）有关，94个与细胞成分（CC）有关，260个与分子功能（MF）有关。KEGG通路分析鉴定出172条通路。分子对接证实了芦荟素与核心靶点的稳定结合。分子动力学模拟通过分析Aloin-target配合物的均方根偏差（RMSD）、均方根波动（RMSF）、旋转半径（Rg）、氢键、溶剂可及表面积（SASA）和吉布斯自由能进一步验证了其结合稳定性。实验验证表明，芦荟素可减轻大鼠CP/CPPS模型的疼痛，降低炎症因子，降低氧化应激。qRT-PCR结果显示，芦荟素干预降低了AKT1、EGFR、HSP90AA1和SRC mRNA的表达，同时增加了ESR1 mRNA的表达。这些变化可能是其治疗CP/CPPS的基础。结论：芦荟素具有减轻CP/CPPS相关疼痛症状、改善炎症、降低氧化应激的作用。通过网络药理学研究，发现了潜在的靶点和信号通路，提示芦荟素对CP/CPPS的治疗前景。这些发现支持进一步探索其治疗CP/CPPS的临床疗效和机制基础。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.