Hua-Tan-Sheng-Jing Decoction Treats Obesity With Oligoasthenozoospermia by Up-Regulating the PI3K-AKT and Down-Regulating the JNK MAPK Signaling Pathways: At the Crossroad of Obesity and Oligoasthenozoospermia

Abstract

Background: Oligoasthenozoospermia is the leading cause of male infertility, seriously affecting men’s health and increasing the societal medical burden. In recent years, obesity-related oligoasthenozoospermia has attracted increased attention from researchers to find a cure. This study aimed to evaluate the efficacy of Hua-Tan-Sheng-Jing decoction (HTSJD) in treating obesity with oligoasthenozoospermia, determine its active ingredients and identify its mechanism of action.Methods: The ingredients of HTSJD were determined by combining the ultra-performance liquid chromatography with mass spectrometry (UPLC-MS/MS) and systems pharmacology approach. The common pathogenesis of obesity and oligoasthenozoospermia and the potential mechanism of HTSJD against obesity with oligoasthenozoospermia were obtained through target fishing, network construction, and enrichment analyses. Further, molecular docking of the key ingredients with the upstream receptors of the key signaling pathways of the potential mechanism was used to predict their affinity. Finally, high-fat-induced obesity with oligoasthenozoospermia rat model was constructed to determine the effects of HTSJD on semen concentration, sperm motility, body weight, and serum lipid metabolism. The key proteins were validated by immunohistochemistry (IHC).Results: A total of 70 effective components and 847 potential targets of HTSJD (H targets) were identified, of which 743 were common targets related to obesity and oligoasthenozoospermia (O-O targets) mainly enriched in the pathways related to inflammation, oxidative stress and hormone regulation. Finally, 143 common targets (H-O-O targets) for HTSJD against obesity with oligoasthenozoospermia were obtained. Combining the hub genes and the results of Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of H-O-O targets, PI3K-AKT and MAPK signaling pathways were identified as the key pathways. Molecular docking results showed that Diosgenin, Kaempferol, Quercetin, Hederagenin, Isorhamnetin may act on the related pathways by docking EGFR, IGF1R and INSR. The animal-based in vivo experiments confirmed that HTSJD improves the sperm quality of high-fat diet-fed rats by reducing their body weight and blood lipid levels, influencing the PI3K-AKT and MAPK signaling pathways and altering the corresponding protein expressions.Conclusion: HTSJD treats obesity with oligoasthenozoospermia by up-regulating the PI3K-AKT signaling pathway and down-regulating the MAPK signaling pathway, which are at the crossroad of obesity and oligoasthenozoospermia.

Integrating network pharmacology and animal experimental validation to investigate the action mechanism of oleanolic acid in obesity

“…The core anti-obesity targets of OA were selected for molecular docking, and all macromolecular structures were re-docked before formal docking. The RMSD values for all of them were less than 2A, indicating good precision and a good binding pattern [ 42 ]. It is widely accepted that a lower binding energy indicates a more stable binding of ligand and receptor, suggesting that the chemical is more likely to interact with the protein.…”

Yangjing capsule improves oligoasthenozoospermia by promoting nitric oxide production through PLCγ1/AKT/eNOS pathway

“…( Schnabel et al, 2005 ). Using the network pharmacology technique, Chen et al discovered that the AKT pathway has a substantial role in oligoasthenozoospermia and was associated with the Yishen Tongluo formula used to treat the condition ( Dong et al, 2022 ). Panax ginseng glycoproteins regulate AKT signaling and promote sex hormones, sperm quality, and the differentiation process in a murine model of oligoasthenozoospermia ( Shan et al, 2021 ).…”