Understanding The Link Between BPH And ED — Why Treating One Can Help The Other

ABSTRACT：

Objective To explore the mechanism of Capsulein 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 were collected and obtained based on TCMSP, BATMAN, PubChem, and Swiss Target Prediction databases, and the BPH and ED target genes were predicted by the 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 the 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 were obtained, including crocetin, lycium barbarum alcohol, 3,9-di-o-methylnisolin, quercetin, kaempferol, etc; 146 " drug disease" intersection targets. 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), the 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 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： Dichen Kangka Capsule; Qianlie Tongqiao Capsule; benign prostatic hyperplasia; erectile dysfunction; homotherapy for heteropathy; network pharmacology; molecular docking

 

 

Benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are two of the most common urological health issues in middle-aged and older men. BPH mainly causes frequent urination, night-time urination, incomplete emptying, and weak urine flow, while ED is marked by difficulty achieving or maintaining an erection.

With rising living standards, both conditions now have a significant impact on men's physical and mental health. According to epidemiological studies:

The prevalence of BPH/LUTs (lower urinary tract symptoms) is 50%–75% among men over 50, and up to 80% in men over 70.

ED affects 23.56% of men aged 50–59, 48.37% in those 60–69, and 81.60% of men over 70.

This shows that age is a major risk factor for both BPH and ED. In fact, studies show that around 70% of men with BPH/LUTs also suffer from ED, and they share many of the same risk factors.

In traditional Chinese medicine (TCM), ED is often caused by kidney deficiency, liver stagnation, and blood stasis, while BPH symptoms like difficult or frequent urination are linked to kidney and qi deficiency, and poor blood flow. Treatments usually focus on boosting energy (qi), nourishing the kidneys, and improving circulation. TCM herbal pairs like Astragalus–Leech and Lindera–Alpinia are commonly used.

Our research team believes that qi deficiency is a key underlying cause of both BPH and ED. Qi deficiency can lead to poor blood flow and blocked circulation, causing ED, and can also affect the body's ability to regulate urination, worsening BPH. That's why we advocate a treatment principle of "tonifying qi and kidney, activating blood, and clearing blockages"-a shared solution for both conditions.

Dichen Kangka Capsuleis a patented formula developed by Prof. Zhang Chunhe, a leading TCM urologist in China. It was upgraded from granule form to capsule for better absorption and convenience.'s traditional effects are to boost energy, improve blood flow, nourish the kidneys and unblock channels (the "orifices"). It's widely used to treat male reproductive and urinary issues in TCM.

Previous studies have shown that improves BPH and urinary symptoms. In our clinical practice, many patients report that, while their urination improves, their erection quality and ejaculation strength also get better. We believe this is because QTC targets the shared root causes of BPH and ED, achieving "treating different diseases with the same method". However, the exact mechanism is still unclear.

That's why we are now using modern pharmacology and molecular docking technology to explore how QTC works on both BPH and ED, laying the groundwork for future scientific research.

1. Materials and Methods

1.1 Identifying Active Compounds and Targets in Cistanche Formula (QTC)

We used well-known databases like TCMSP and BATMAN-TCM to collect the active ingredients in the herbal formula Dichen Kangka Capsule (QTC), which includes Cistanche, Astragalus, Leech, Lindera, Alpinia, Achyranthes, and Cinnamon. Filtering conditions were:

Oral bioavailability ≥ 30%

Drug-likeness ≥ 0.18 (TCMSP)

Score ≥ 20 (BATMAN)

Next, we retrieved SMILES structures from PubChem and predicted related human protein targets using Swiss Target Prediction. Targets with zero probability were excluded. We finalized a clean target list after removing duplicates.

 

1.2 Finding Disease-Related Targets for BPH (Benign Prostatic Hyperplasia) and ED (Erectile Dysfunction)

We searched GeneCards using the keywords "benign prostatic hyperplasia" and "erectile dysfunction". Targets were filtered using the median relevance score. After deduplication, we compiled lists of 987 targets for BPH and 1,162 for ED.

We then compared these with the targets from QTC (including Cistanche extract) to find overlapping targets. A total of 146 shared targets were identified. (See Figure 1)

 

1.3 Building the "Herb–Compound–Target–Disease" Network

We used Cytoscape 3.10.0 to build a visual network showing how the herbs (especially Cistanche) interact with active compounds, protein targets, and diseases. The Analyze Network tool helped us identify the core active ingredients.

1.4 Constructing the Protein–Protein Interaction (PPI) Network

The 146 shared targets were uploaded to the STRING database, using Homo sapiens as the organism and a confidence level > 0.4 to build the PPI network. The data was imported into Cytoscape, and key proteins were identified using cytoHubba and Network Analyzer.

 

1.5 Biological Function and Pathway Analysis

We used the Metascape platform to conduct GO (Gene Ontology) and KEGG pathway enrichment analysis on the 146 targets. Criteria:

Species: Homo sapiens

Enriched targets > 3 and P < 0.01

We visualized the top 20 results across:

Biological Process (BP)

Cellular Component (CC)

Molecular Function (MF)

KEGG Pathways

Dichen Kangka tablets

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1.6 Molecular Docking Simulations

Molecular docking was done using MOE software. First, we downloaded the 2D structures of key compounds (like those in Cistanche) from PubChem, then minimized their energy states. Protein structures were taken from the Protein Data Bank, and pre-processed (water and ions removed). Full-atom docking was performed.

Binding energy values less than -5 were considered strong interactions, indicating that the compound may effectively bind to the protein target.

 

2. Results

2.1 Active Compounds and Targets from QTC (Cistanche-Based Formula)

After screening:

Cistanche: 10 active ingredients

Astragalus: 19

Lindera: 9

Alpinia: 4

Leech: 13

Cinnamon: 17

Achyranthes: 4

After removing duplicates, we identified a total of 70 unique compounds in the formula. From these, we predicted and cleaned a list of 879 unique protein targets.

 

2.2 Disease Targets and Overlapping Targets with QTC

BPH-related targets: 987

ED-related targets: 1,162

Overlapping targets with QTC: 146

This overlap shows that QTC, especially its Cistanche extract, may act on multiple pathways shared by both diseases.

 

 

 

Table 1: Active Compounds of QTC (Dichen Kangka Capsule)

Herb	Code	Chemical Compound	Herb	Code	Chemical Compound
Astragalus	HQ1	1,7-Dihydroxy-3,9-dimethoxy pterocarpene	Leech	SZ10	D-Mannitol
	HQ2	Marian		SZ11	Ursolic acid
	HQ3	Jaranol		SZ12	Gardenoside
	HQ4	(3S,8S,9S,10R,13S,14S,17R)-10,13-dimethyl-17-[(2R,5S)-5-propan-2-yl-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol	Lindera	WY1	6,7-dimethoxy-2-(4-methoxyphenyl)chromone
	HQ5	7-O-methylisomucronulatol		WY2	DMPPEC
	HQ6	(6α,11R,1αR)-9,10-dimethoxy-6α,11α-dihydro-6H-benzo[f,3,2-b]chromen-3-ol		WY3	Phenethyl cinnamate
	HQ7	Bifendate		WY4	CN09495
	HQ8	Calycosin	WY5	Unbiogool
	HQ9	FA	Alpinia	YZR1	Boldine
	HQ10	(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol		YZR2	Isorhamnetin
	HQ11	Isomucronulatol-7,2′-di-O-glucoside		YZR3	Sitosterol palmitate
Cistanche	RG1	Acteoside	Achyranthes	CNX1	Protocatechuic acid
	RG2	Isoacteoside		CNX2	Vanillic acid
	RG3	Pinoresinol		CNX3	Ferulic acid
	RG4	Cinnamic alcohol		CNX4	3,4-dihydroxybenzoic acid
	RG5	Anethole		CNX5	Rosmarinic acid
	RG6	Procumbenoside B2		CNX6	Chlorogenic acid
Dodder Seed	TSZ1	NSC63531		CNX7	Protocatechuic aldehyde
	TSZ2	Stigmasterol	CNX8	Isochlorogenic acid
	TSZ3	Campest-5-en-3β-ol	CNX9	3,4-Dihydroxybenzenepropanoic acid
	TSZ4	GLR	Multi-herb	CY1	(−)-Epicatechin-3-O-gallate
	TSZ5	Matrine		CY2	Trans-cinnamic acid
	TSZ6	NSC63531		CY3	Vanillic acid
Leech	SZ4	Myricanone	CY4	Beta-sitosterol
	SZ5	Crocetin			CY5	Ferulic acid
	SZ6	Aurantiamide acetate
	SZ7	Gardenin A
	SZ8	Gardenin B
	SZ9	L-acetylcarnitine

 

 

Figure 1. Venn diagram of the intersection targets of BPH and ED in QTC's "different diseases treated with the same method"

 

2.3 Construction and analysis of the "drug-ingredient-target-disease" network According to the method, the "drug-disease" intersection target was input into the Cytoscape 3.10.0 software to obtain the "drug-ingredient-target-disease" network diagram (Figure 2). After calculation, the top 10 active ingredients were selected. See Table 2.

 

Table 2: Top 10 Active Compounds in QTC by Degree Value

Code	Active Compound	Degree Value	Herbal Source
HQ12	(3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol	41	Astragalus
HQ7	(6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano[3,2-c]chromen-3-ol	37	Astragalus
SZ9	Crocetin	34	Leech
WY6	Boldine	33	Lindera
HQ3	Jaranol	32	Astragalus
HQ5	3,9-di-O-methyl nissolin	31	Astragalus
HQ17	Isoflavanone	31	Astragalus
GY2	Kaempferol	31	Astragalus, Dodder Seed, Lindera, Achyranthes
GY3	Quercetin	30	Astragalus, Dodder Seed
RG3	Melilotocarpan A	28	Cinnamon