Phosphodiesterase‐5 Inhibitory Activity of Canthin‐6‐One Alkaloids and the Roots of Eurycoma longifolia and Eurycoma harmandiana

Abstract Eurycoma longifolia (EL) and Eurycoma harmandiana (EH) are natural medicinal plants belonging to the Simaroubaceae family, and are well‐known for their ability to enhance male sexual performance. The present study investigated the phosphodiesterase‐5 (PDE‐5) inhibitory activity of intact roots of EL and EH. Additionally, canthin‐6‐one alkaloids, β ‐carboline alkaloids, and quassinoids were also screened for PDE‐5 inhibitory activity. We developed in vitro root and callus cultures of EL and EH to determine their PDE‐5 inhibitory activity. Our results indicated that canthin‐6‐one alkaloids, which include canthin‐6‐one‐9‐ O ‐ β ‐D‐glucopyranoside, 9‐methoxycanthin‐6‐one, canthin‐6‐one, and 9‐hydroxycanthin‐6‐one, exhibited PDE‐5 enzymatic inhibitory activity, with IC 50 values of 2.86±0.23, 3.30±1.03, 4.31±0.52, and 4.66±1.13 μM, respectively. The ethanolic extract of the intact roots of EL and EH, and the in vitro root culture of EH had large amounts of canthin‐6‐one alkaloids (1.50±0.04, 2.12±0.03, and 3.48±0.08 mg/g dry weight, respectively), and showed potent PDE‐5 inhibition. Our findings indicate that in vitro root cultures of EH may be used to replace intact plants, and canthin‐6‐one‐9‐ O ‐ β ‐D‐glucopyranoside should be further investigated for development as a health supplement.