Mechanism of Shenqi Qiangjing Granules in Treating Cyclophosphamide‐Induced Oligozoospermia Based on Network Pharmacology and Experimental Validation

Research indicates that cyclophosphamide (CY), a cancer treatment, can cause oligozoospermia in men. Traditional Chinese medicine, particularly Shenqi Qiangjing (SQ) granules, may help improve this issue, but the exact way it works against CY–induced oligozoospermia is not completely clear. This study aimed to verify that SQ can improve oligozoospermia caused by CY and explore its potential mechanism. This research uses network pharmacology to identify common genes linked to SQ and oligozoospermia, as well as testicular macrophage polarization (TMP). Using databases such as TCMSP and GeneCard, relevant genes were identified, and a protein interaction network was created with STRING and Cytoscape. GO and KEGG analyses was used to identify pathways related to SQ. To induce oligozoospermia, male mice were given a 60 mg/kg dose of CY for 5 days. The plants were then treated with two doses of SQ (200 and 800 mg/kg) for 21 days to assess its protective effects on reproductive organs. Measurements included testicular and epididymal indices, sperm quality, hormone levels, oxidative stress markers, inflammatory cytokines, tissue changes, and proteins related to the nuclear factor κB (NF‐κB) pathway. Researchers identified 883 genes linked to SQ, with 16 key genes that help improve oligozoospermia by affecting TMP. Analysis suggests that SQ may promote oligozoospermia by regulating TMP through NF‐κB. Studies have shown that SQ improves sperm quality, reduces oxidative damage, balances sex hormones, shifts macrophages from the M1 phenotype to the M2 phenotype, and decreases NF‐κB protein levels. SQ alleviates oligozoospermia by reversing M1 macrophage polarization via NF‐κB, supporting its potential in treating male infertility and aligning with national fertility strategies.