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. 2021 Apr 30;13(3):351-358.
doi: 10.1016/j.chmed.2021.04.016. eCollection 2021 Jul.

Mechanism of Huoxue Tongluo Decoction in treatment of erectile dysfunction caused by ischemic stroke based on network pharmacology

Ji-Sheng Wang  1   2 , Heng-Heng Dai  1   2 , Kai-Ge Zhang  1   2 , Ke-Gang Cao  2   3 , Sheng Deng  1   2 , Bing-Hao Bao  1   2 , Jun-Long Feng  1   2 , Fan-Chao Meng  1   2 , Hai-Song Li  2 , Bin Wang  2
Affiliations

Mechanism of Huoxue Tongluo Decoction in treatment of erectile dysfunction caused by ischemic stroke based on network pharmacology

Ji-Sheng Wang et al. Chin Herb Med. .

Abstract

Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved.

Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue.

Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05).

Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.

Keywords: Huoxue Tongluo Decoction; erectile dysfunction; ischemic stroke; network pharmacology.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Venn diagram. Intersection of IS target and ED target (A); intersection of HXTLD target, IS target and ED target (B).
Fig. 2
Fig. 2
Network construction of herbal medicine-active ingredient-target-disease. The red node represents ISED, the blue diamond represents HXTLD, the green square represents herbal medicine, the yellow circle represents the active ingredient, and the pink triangle represents the target.
Fig. 3
Fig. 3
PPI network diagram. (A) PPI network established by Cytoscape (3.7.1), the red node is the first five key nodes processed by cytohubba, and the size of the node is proportional to the “degree” of the node; (B) PPI network processed by the plug-in (cytohubba), the color of the node is proportional to the “degree”.
Fig. 4
Fig. 4
GO and KEGG enrichment analysis. (A) GO item analysis: the red bar represents BP, the yellow bar represents CC, and the blue bar represents MF (a: response to DNA damage b: synaptic transmission, dopaminergic c: neuron apoptotic process d: lipopolysaccharide-mediated signaling pathway e: protein kinase B signaling f: extracellular space g: axon h: blood microparticle i: extracellular region j: integral component of plasma membrane k: growth factor activity l:drug binding m: dopamine binding n: nitric-oxide synthase activity o: flavin adenine dinucleotide binding). (B) KEGG pathway enrichment: X-axis represents rich factor, Y-axis represents name, node size is related to count, and node color is related to P value.
Fig. 5
Fig. 5
HE staining results of cavernous body of penis. The trabecular sponge and sinuses were evenly distributed in the cavernous body in the S group of rats. The density of endothelial cells and smooth muscle cells in group M decreased significantly. The sinusoidal distribution of rats in the T group was more regular, the density of endothelial cells increased, and red blood cells were visible in some sinusoidal spaces.
Fig. 6
Fig. 6
Expression of TNF, eNOS and VEGF protein in cavernous body of penis by Western blotting analysis. **P < 0.01 compared with S group, #P < 0.05 compared with M group.
Fig. 7
Fig. 7
Expression of TNF, eNOS and VEGF mRNA in cavernous body of penis by Real-time PCR analysis. **P < 0.01 compared with S group; #P < 0.05 compared with M group.
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