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. 2024 Nov-Dec;18(6):15579883241293936.
doi: 10.1177/15579883241293936.

Bioinformatics Combined With Experimental Modeling to Study the Molecular Mechanism of Xuefu Zhuyu Decoction to Improve Erectile Dysfunction Associated With Asthma in Rats

Junlong Feng  1   2 , Sheng Deng  3 , Xuefeng Gong  4 , Bin Wang  1 , Longji Sun  1 , Huanan Zhang  1 , Zixiang Gao  1   2 , Hui Chen  1   2 , Kali Zou  5 , Jiaqi Yang  1   2 , Haisong Li  1 , Jisheng Wang  1
Affiliations

Bioinformatics Combined With Experimental Modeling to Study the Molecular Mechanism of Xuefu Zhuyu Decoction to Improve Erectile Dysfunction Associated With Asthma in Rats

Junlong Feng et al. Am J Mens Health. 2024 Nov-Dec.

Abstract

Asthma is associated with chronic systemic inflammation, and inflammatory factors can damage vascular endothelial cells, thus impairing erectile function (ED). Xuefu Zhuyu decoction (XFZYD) can inhibit inflammation and promote angiogenesis, which in turn improves asthma as well as ED, but its exact mechanism of action is not yet clear. This study investigates the mechanism underlying the beneficial effect of XFZYD on asthma-associated ED. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to analyze the constituents of XFZYD, and network pharmacology analysis was used to predict the target genes of XFZYD. Sprague-Dawley rats in the asthma model with erectile dysfunction were divided into the model, XFZYD low-, medium-, and high-dose group (3.09, 6.17, and 12.34 g/kg), with drug intervention for 8 weeks. We assessed the interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), and tumor necrosis factor (TNF) protein levels in the penile tissue. We discovered that after treatment with XFZYD (3.09, 6.17, and 12.34 g/kg), the number of erections significantly increased (1.17 ± 0.41, 1.50 ± 0.55, and 1.67 ± 0.52), the density of endothelial cells in the corpus cavernosum of the penis increased, the expression level of IL-6 was reduced (7.5%, 21.2%, and 24.4%), the expression level of VEGFA was reduced (7.8%, 25%, and 28.4%), and the expression level of TNF was reduced (13.5%, 30.6%, and 32.4%). The in vivo experiments indicate that XFZYD may improve ED in asthma model rats by inhibiting inflammation and reducing vascular permeability. This study provides new insights into the mechanism of action of XFZYD in the treatment of asthma leading to ED.

Keywords: classical formula; erectile dysfunction; network pharmacology; target.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
(A) Intersection of Xuefu Zhuyu Decoction Targets, Asthma Targets, and Erectile Dysfunction Targets; (B) PPI Network Built by Cytoscape (3.7.1); (C) PPI Network Processed by Cytoscape (3.7.1) Plugin (cytoHubba)
Figure 2.
Figure 2.
The Network Construction for Herbal–Compound–Targets–Disease
Figure 3.
Figure 3.
Analyses of Pathway Enrichment Using GO and KEGG Databases
Figure 4.
Figure 4.
HE Staining of Lung Tissue in Groups C and M (×100 and ×400). (A) In Group C: The Alveolar Walls Were Clear and Complete, the Bronchial Lumen Was Regular, the Smooth Muscle and Blood Vessel Walls Were Not Significantly Thickened, and There Was No Obvious Inflammatory Cell Infiltration (Arrows ①②③④). (B) In Group M: The Lung Tissue Structure Was Disordered, Incomplete Alveolar Walls, Massive Infiltration of Inflammatory Cells Around the Trachea and in the Pulmonary Interstitium, and Thickening of Smooth Muscle and Vascular Walls (Arrows ⑤⑥⑦⑧)
Figure 5.
Figure 5.
ROS Levels in Rats in Each Group After Drug Intervention (×100, Black = 5, Gamma = 1, White = 255)
Figure 6.
Figure 6.
HE Staining of Penile Tissue of Rats From the C, M, and T Groups (×200 and ×400). (A) In the C Group: The Blood Sinuses Were Evenly Distributed, With Red Blood Cells in the Sinus Space and Endothelial Cells Covering the Inner Wall (Arrows ①②). (B) In the M Group: The Distribution of Blood Sinusoids Was Disordered, and the Density of Endothelial Cells and Smooth Muscle Cells Was Reduced (Arrows ③④). (C) In the D, Z, and G Group: The Distribution of Blood Sinuses Was More Regular and the Density of Endothelial Cells Was Increased, the Number of Collagen Fibers Was Relatively Reduced (Arrows ⑤⑥⑦⑧⑨⑩).
Figure 7.
Figure 7.
(A) Electrophoretogram of Three Proteins (IL6, VEGFA, TNF, eNOS) in Rats From the C, M, D, Z, and G Groups. (B) The Expression Levels of Three Proteins (IL6, VEGFA, TNF, eNOS) in Rats From the C, M, D, Z, and G Groups Determined Using Western Blotting. (C) The mRNA Expression Levels of Three Proteins (IL6, VEGFA, TNF, eNOS) in Rats From the C, M, D, Z, and G Groups Determined Using Western Blotting. Note. Data are expressed as the mean ± SEM. Differences with p < .05 were considered statistically significant. # p < .05, the M group versus the C group; *p < .05, the D, Z, and G groups versus the M group.
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