Integrated network pharmacology, molecular docking and in vivo experiments to elucidate the extenuative mechanisms of ginseng polysaccharide against Toxoplasma gondii-induced testicular toxicity

Chengquan Han; Xin Qi; Xinyu Liu; Minjie Hu; Qihui Zhao; Lizeng Guan; Lu Xu

doi:10.1016/j.intimp.2025.114147

Integrated network pharmacology, molecular docking and in vivo experiments to elucidate the extenuative mechanisms of ginseng polysaccharide against Toxoplasma gondii-induced testicular toxicity

Int Immunopharmacol. 2025 Jan 24:148:114147. doi: 10.1016/j.intimp.2025.114147. Online ahead of print.

Authors

Chengquan Han¹, Xin Qi², Xinyu Liu¹, Minjie Hu¹, Qihui Zhao¹, Lizeng Guan¹, Lu Xu³

Affiliations

¹ College of Agriculture and Forestry Science, Linyi University, Linyi 276000 Shandong, China.
² College of Agriculture, Yanbian University, Yanji 133000 Jinlin, China.
³ College of Agriculture and Forestry Science, Linyi University, Linyi 276000 Shandong, China. Electronic address: xulu0824@126.com.

PMID: 39862631
DOI: 10.1016/j.intimp.2025.114147

Abstract

Toxoplasma gondii (T. gondii) causes obvious reproductive toxicity in male by inducing inflammation and apoptosis in testicular tissue. Ginseng polysaccharide (GP) is an active compound in ginseng, known for its remarkable anti-inflammatory and antioxidant properties. This study aimed to investigate the effects of GP against T. gondii-induced testicular injury by integrating network pharmacology and in vivo experiments. Totally 9 core targets were identified, and PI3K/AKT1 signaling pathway were enriched via the network pharmacology analysis of GP against T. gondii-induced testicular injury, and molecular docking indicated that TLR4-related inflammatory pathways and Bax-related apoptotic pathways were also involved. In vivo experiments showed that GP (100 or 200 mg/kg) mitigated the histopathology damage, enhanced spermatogenic capacity of the testis, and increased the levels of testosterone, luteinizing hormone and follicular-stimulating hormone in the serum. Proteins related to testosterone biosynthesis, StAR, P450scc and 17β-HSD, were significantly up-regulated. GP also inhibited the levels of inflammatory factors, by inhibiting the TLR4-P2X7R/NLRP3 inflammatory pathway in the testicular tissue. In addition, GP remarkably decreased testicular cell apoptosis rate, activated the PI3K/AKT pathway, and remarkably inhibited the apoptosis-associated PERK/eIF2α/ATF4/CHOP endoplasmic reticulum (ER) stress signaling pathway. In conclusion, the extenuative mechanisms of GP against T. gondii-induced testicular toxicity were comprehensively identified through integrating network pharmacology with in vivo experiments, it suggested that GP alleviates T. gondii-induced testicular toxicity by inhibiting the TLR4-P2X7R/NLRP3 inflammatory and PERK/eIF2α/ATF4/CHOP ER stress signaling pathways. This study provides new evidence for further development of ginseng as healthcare products to improve male reproductive function in T. gondii-infected patients.

Keywords: Ginseng polysaccharide; Molecular docking; Network pharmacology; PI3K/AKT signaling pathway; Toxoplasma gondii-induced testicular tissue injury.