Molecular mechanisms of sea cucumber bioactive compounds in anti-infertility treatment: In silico and In vivo approach

Infertility affects 15% of couples worldwide and is often associated with oxidative stress and inflammation. Sea cucumbers, traditionally used in medicine, may offer a promising new approach to infertility treatment due to their beneficial properties, although the underlying mechanisms remain not fully understood. This study aimed to elucidate the molecular mechanisms underlying the anti-infertility effects of sea cucumber using a network pharmacology approach, with a focus on interactions with key hormone receptors and signaling pathways and in vivo study. This experimental study employed in silico and in vitro methods to evaluate the potential of Stichopus herrmanni extracts in the treatment of infertility. Bioactive compounds from sea cucumber extracts were identified via LC-MS. The potential for infertility treatment was assessed using the WAY2DRUG PASS server, while ADMET analysis determined drug-likeness. Protein targets were predicted using the SEA Search Server and Swiss Target Prediction, and cross-referenced with the DisGeNET and Open Targets databases. Network topology analysis was conducted using STRING and Cytoscape. Docking analysis and molecular dynamics simulations were performed to investigate interactions with estrogen receptor alpha (ESR1) and androgen receptor (AR). In vivo tests involved administering 300 mg/kg of sea cucumber extract to male rats with regular or high-fat diets for eight weeks. Twentynine bioactive compounds exhibited anti-infertility potential. Notably, andrographolide and 6-gingerol strongly bound to ESR1 and AR, with stable interactions confirmed by molecular dynamics. In vivo , the extract reduced oxidative stress by increased GSH, inflammation by decreased NfkB and weight gain in high-fat diet rats. This study supports the anti-infertility potential of bioactive compounds derived from sea cucumber, highlighting their promising therapeutic effect on infertility through antioxidant, anti-inflammatory mechanism. Specifically, Andrographolide and 6-gingerol show promise as natural modulators of estrogen signaling. offering potential for improved reproductive health outcomes.