Molecular docking and dynamics reveal potential galactagogue mechanism of Breynia patens via D2R, OXTR, and TRβ modulation

This study investigates the in-silico interactions of 17 active components from Breynia patens extract with lactation-related proteins. The compounds were first screened via rigid docking using AutoDock Vina against three target receptors: dopamine receptor D2R, oxytocin receptor OXTR, and thyroid hormone receptor TR β . Furthermore, flexible docking (AGFR) used to refine the results. The interaction between Stigmasterol and D2R further analysed by employing molecular dynamics (MD) simulations of 300 ns using Dopamine as a control. The lactation-related role of receptors was analysed by KEGG enrichment using the DAVID database. Rigid docking identified promising candidates, and flexible docking revealed that 11 of the 17 components strongly interacted with D2R. Stigmasterol (-9.6 kcal/mol), epifriedenalol (-9.0 kcal/mol), and β-sitosterol (-8.2 kcal/mol) exhibited the highest binding affinities. Three compounds; glochidonol, lupeol, and friedelanol interacted with the allosteric site of OXTR (-8.0, -7.2, and -7.8 kcal/mol), while quercetin (-6.8 kcal/mol) and kaempferol (-6.2 kcal/mol) interacted with TR β . MD simulations showed Stigmasterol maintained interaction with the D2R active site for 300 ns, though with lower stability compared to dopamine, suggesting possible antagonism. KEGG enrichment confirmed all three receptors as part of hormone signaling pathways linked to lactation. This in-silico analysis suggests Breynia patens may promote lactation via multi-receptor modulation, including D2R antagonism, OXTR allosteric modulation, and TR β partial agonism. These findings align with its traditional galactagogue use, but experimental validation is required to confirm therapeutic relevance.