Mechanism Of Qizhi Tongqiao Capsule in Treating Benign Prostatic Hyperplasia And Erectile Dysfunction Based On Network Pharmacology And Molecular Docking
Mar 03, 2025
ABSTRACT：
Objective To explore the mechanism of Qizhi Tongqiao Capsule (QTC) in treating benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) based on network pharmacology and molecular docking technology. Methods The active ingredients and corresponding targets of QTC were collected and obtained based on TCMSP, BATMAN, PubChem and Swiss Target Prediction databases, and the BPH and ED target genes were predicted by GeneCards database. The intersection targets were obtained by Venny 2.1, and the "drug component target disease" visual network diagram was constructed by Cytoscape 3.10.0. The protein interaction (PPI) network was constructed based on STRING database, and then imported into Cytoscape 3.10.0 to output the core targets, Metascape database for GO function and KEGG pathway enrichment analysis. Finally, molecular docking was carried out testing. Results A total of 70 active components of QTC were obtained, including crocetin, lycium barbarum alcohol, 3,9-di-o-methylnisolin, quercetin, kaempferol, etc; 146 " drug disease" intersection targets. QTC may act on multiple targets such as serine/threonine protein kinase 1 (AKT1), interleukin-6 (IL6), estrogen receptor (ESR1), signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), jun transcription factor (JUN), regulator of apoptosis (BCL2), caspase -3 (CASP3), and regulate NF -κB signaling, diabetic complications, calcium ion and other related signaling pathways. Molecular docking results showed that quercetin was well docked with the core target. Conclusion QTC may play a role in treating BPH and ED by regulating NF-κB signaling pathway, diabetes complications related pathway and calcium ion signaling pathway based on AKT1, IL6, ESR1, STAT3, TNF, JUN, BCL2, CASP3 and other targets, but it still needs to be verified in further research.
KEYWORDS：Qizhi Tongqiao Capsule; Qianlie Tongqiao Capsule; benign prostatic hyperplasia; erectile dysfunction; homotherapy for heteropathy; network pharmacology; molecular docking
Herbal Cistanche Supplement for Benign Prostatic Hyperplasia (BPH)
Benign Prostatic Hyperplasia (BPH) and Erectile Dysfunction (ED) are common urological and andrological disorders in middle-aged and elderly men. BPH and ED manifest clinically as lower urinary tract symptoms (LUTs) such as urinary frequency, nocturia, incomplete voiding, and dysuria, as well as penile erectile insufficiency, easy detumescence, difficulty in achieving or maintaining erections, respectively [1-2]. With the continuous improvement in living standards in China, both conditions significantly impact the physical and mental health of middle-aged and elderly men. Epidemiological studies report that the prevalence of BPH/LUTs reaches 50%-75% in males aged 50 years or older, increasing to 80% in those aged 70 years or older, with age being a key risk factor [3]. Similarly, ED prevalence progressively rises with age: 23.56% in males aged 50-59 years, 48.37% in those aged 60-69 years, and 81.60% in males over 70 years [4]. Notably, approximately 70% of BPH/LUTs patients concurrently suffer from ED, sharing common risk factors according to Calogero et al. [5-6].
From the perspective of Traditional Chinese Medicine (TCM), the fundamental pathogenesis of ED is attributed to kidney deficiency (shenxu), liver stagnation (ganyu), and blood stasis (xueyu) [2]. BPH-induced LUTs, corresponding to the TCM concept of "dysuria" (xiaobian buli), primarily result from kidney deficiency with blood stasis and qi deficiency impairing urinary propulsion, leading to symptoms like urinary hesitation and weak stream [1,7]. The therapeutic principles emphasize tonifying qi, nourishing the kidneys, and removing stasis to unblock orifices. Commonly used herb pairs include Astragalus-Hirudo (Huangqi-Shuizhi) and Lindera Root-Combined Spicebush Fruit (Wuyao-Yizhiren). Our research team proposes that qi deficiency (particularly kidney qi deficiency) serves as a critical pathogenic mechanism in both BPH and ED. Qi deficiency leads to blood stasis, causing malnourishment of the penile vessels (zongjin) in ED, and impaired qi transformation contributing to urinary dysfunction in BPH. Thus, we posit that "qi deficiency with blood stasis" constitutes the shared pathogenesis of BPH, ED, and their comorbidity, warranting a unified therapeutic strategy of "tonifying qi, activating blood circulation, nourishing kidneys, and resolving stasis" for these disorders [8-9].
Qizhi Tongqiao Capsule (QTC), developed by Prof. Zhang Chunhe (Director of Andrology Department at Yunnan Provincial Hospital of Traditional Chinese Medicine and Vice Chairman of Andrology Branch of China Association of Chinese Medicine), is a modified capsule formulation derived from a granule preparation [10-12]. Functioning to "tonify qi, activate blood circulation, nourish kidneys, and unblock collaterals" for orifice disorders, QTC has demonstrated efficacy in improving BPH/LUTs in preliminary studies [12]. Notably, clinical observations revealed that patients receiving QTC for BPH often reported concurrent improvements in erectile rigidity and ejaculatory force during follow-up. This suggests QTC's potential "disease-differentiation with shared treatment" effect by targeting the common pathogenesis of both conditions. However, the underlying mechanisms remain unclear. This study aims to investigate the therapeutic mechanisms of QTC for BPH and ED comorbidity through network pharmacology and molecular docking approaches, providing a theoretical foundation for subsequent experimental validation.
1.1 Acquisition of QTC Active Components and Targets
The active components of the herbal constituents in QTC (Astragalus membranaceus, Hirudo nipponica, Cuscuta chinensis, Lindera aggregata, Alpinia oxyphylla, Cyathula officinalis, and Cinnamomum cassia) were retrieved from the TCMSP [13] and BATMAN [14] databases. The screening criteria for TCMSP and BATMAN were set as oral bioavailability (OB) ≥ 30%, drug-likeness (DL) ≥ 0.18, and Score ≥ 20, respectively. The SMILES numbers of the active components were obtained from the PubChem database and input into the Swiss Target Prediction database [15], with the species set to Homo sapiens. Targets with a probability of 0 were excluded, and duplicate targets were removed.
1.2 Prediction of BPH and ED-Related Targets
Using the keywords "benign prostatic hyperplasia" and "erectile dysfunction," relevant targets were retrieved from the GeneCards database [16]. The median relevance score was used as the cutoff value to filter and deduplicate disease-related targets [17]. The intersection of disease targets and QTC active component targets was identified using Venny 2.1.
1.3 Construction of the "Drug-Component-Target-Disease" Network
The "Drug-Component-Target-Disease" network was visualized using Cytoscape 3.10.0. The network was analyzed using the Analyze Network function to calculate topological parameters and identify core active components.
1.4 Construction of the Protein-Protein Interaction (PPI) Network
The intersection targets were uploaded to the STRING database, with the species set to Homo sapiens and a medium confidence threshold of > 0.4 to construct the PPI network. The PPI data were then imported into Cytoscape 3.10.0, and core proteins were identified using the cytoHubba and Network Analyzer plugins.
1.5 Biological Function Prediction
The intersection targets were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the Metascape database [18]. The species was set to Homo sapiens, and enriched targets with > 3 entries and P < 0.01 were selected. The top 20 terms for biological processes (BP), cellular components (CC), molecular functions (MF), and KEGG pathways were visualized [17].
1.6 Molecular Docking
Molecular docking was performed using MOE software. The 2D structures of the active components were obtained from the PubChem database and imported into MOE for energy minimization. Protein structures were retrieved from the Protein Data Bank (PDB) and preprocessed by removing water molecules and ions. Full-atom docking simulations were conducted, and binding energies were calculated. A binding energy value < -5 kcal/mol indicated a favorable docking interaction, and the results were visualized in 3D structures.
