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.
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