Caesalpinia sappan L. Wood is a potential source of natural phosphodiesterase-1 inhibitors

Introduction: A decrease in cAMP and cGMP levels in the brain is linked to human cognitive problems. The degradation of cellular cAMP and cGMP is attributed to phosphodiesterases (PDEs), which constitute a superfamily of enzymes. The inhibition of PDE1 is a promising mechanism to increase cAMP and cGMP levels associated with cognitive disorders. Caesalpinia sappan L. (CS) wood is a natural coloring agent usually consumed as a traditional refreshment or drink by people in Yogyakarta, Indonesia. However, scientific evidence regarding the inhibitory activity of CS wood against PDE1 has yet to be obtained. This study aimed to investigate the potency of CS wood as a PDE1 inhibitor. Methods: The ethanol extract of CS wood and its fractions were evaluated in vitro by using a cyclic nucleotide phosphodiesterase assay kit. The presence of brazilin in the extract and fractions was analyzed by thin-layer chromatography. In silico assay was performed using MOE software to obtain insights into the interaction between compounds in the CS wood and the enzyme. Results: Ethanol extract and ethyl acetate soluble fraction effectively inhibited the PDE1 activity. Interestingly, brazilin, the major compound in CS wood, also exhibited a potent inhibitory effect on the enzyme. The in silico assay revealed that the interaction between tetraacetylbrazilin and brazilin with the PDE1B active site involved hydrogen bonding and �-� interactions. Conclusion: Ethanol extract, ethyl acetate soluble fraction, and brazilin inhibited the PDE1 activity. CS wood and its chemical constituent could be developed as natural cognitive enhancers. © 2020 Elsevier B.V., All rights reserved.