Antihypoxic Action of Panax Japonicus, Tribulus Terrestris and Dioscorea Deltoidea Cell Cultures: In Silico and Animal Studies

Chemical diversity of secondary metabolites provides a considerable variety of pharmacological actions with a significant extension due to their combinations in plant extracts. Production of plant-derived medicinal products in cell cultures has advantages because of the efficient use of different biotic and abiotic elicitors and better control of the developmental processes. Using PASS software, we predicted biological activity spectra for phytoconstituents identified in cell cultures of Panax japonicus (12 molecules), Tribulus terrestris (4 molecules), and Dioscorea deltoidea (3 molecules). Mechanisms of action associated with the antihypoxic effect were predicted for the majority of molecules. PharmaExpert software allowed analyzing possible synergistic or additive effects of the combinations of phytoconstituents associated with the antihypoxic action. Experimental studies of the antihypoxic effect of the plants' extracts in water and ethanol have been performed in 3 animal models: Acute asphyctic hypoxia (AAH), Acute haemic hypoxia (AHeH), and Acute histotoxic hypoxia (AHtH). Effects of Panax japonicus and Tribulus terrestris preparations exceeded the activity of the reference drug Mexidol in the AHtH model. In the AHeH model, all preparations demonstrated moderate activity; the most potent has been observed for Dioscorea deltoidea. Thus, we found that experimental studies in animal models have confirmed the in silico prediction.

Keywords: QSAR; hypoxia; medicinal plant; natural products; phytocomponents.