In Silico Evaluation of Tocolytic Potential of Phytoconstituents in Five Herbs Traditionally used for Treatment of Preterm Labor

Preterm births are a major clinical problem associated with perinatal mortality, severe neonatal morbidity, and moderate to severe childhood disability. The birth of a preterm neonate can bring with it considerable emotional and economic costs to families, with attendant implications for public-sector services. Several medications, including NSAIDs, are used to inhibit acute preterm labor, but tocolysis by these medicines does not extend pregnancy beyond 1-2 days. Consequently, the objective of this paper was to evaluate tocolytic potentials of phytoconstituents in five herbs traditionally used for treatment of preterm labor by in silico evaluation of the following plants: Alchornea laxiflora (15) leaves, Ricinodendron heudelotii (21), Hibiscus sabdariffa calyx (40), Carica papaya (72), and Piper guineense fruit. Their 3D Structure data file (SDF) structures were obtained from PubChem and docked against a Cyclo-oxygenase protein (5KIR) with Pyrx, which used rofecoxib and celecoxib as standards after the protein was processed by Chimera. Postdocking analysis, absorption-distribution-metabolism-excretion (ADME), and toxicity characteristics were performed with Biodiscovery Studio, SwissADME, and ADMETSAR, respectively. Following computational analysis, some phytoconstituents of these plants: quercetin; (+)- gallocatechin, 3', 4' dihydroflavonol, isorhamnetin, 3- hydroxycoumarin, delphinidin, limetin, riboflavin, quercetin and rutin showed significant binding affinities ranging from (-7.1 to 8.6 Kcal/mol). These molecules may have tocolytic benefits in the treatment of preterm labor; however, lead optimization may be required to change these molecules' ADMET properties without compromising their biological activity, molecular dynamics simulation and a wet laboratory experiment will be required to validate the findings of this in silico study.