Bioactive constituents isolated from the Sri Lankan endemic plant Artocarpus nobilis and their potential to use in novel cosmeceuticals

Abstract

Two novel compounds, dicarbonyl ester (2) and artolankanin A (3) were isolated from the sequential ethyl acetate and ethanol extracts of stem bark of A. nobilis along with the known compounds, artonin E (1) and artobiloxanthone (4) by bioassay-guided fractionation using a combination of normal phase and size exclusion column chromatography. Their structures were elucidated by spectroscopic techniques, including NMR (1H, 13C, APT, 1H–1H COSY, HSQC, and HMBC), Mass, IR, and UV. The isolated compounds were evaluated for DPPH free radical scavenging activity, tyrosinase, elastase, hyaluronidase, and A5-lipoxygenase enzyme inhibitory activities lipopolysaccharide-induced nitric oxide production inhibitory activity in SIM-A9 microglial cells. Artonin E exhibited marked tyrosinase and A5-lipoxygenase enzyme inhibitory activities and NO inhibition activity in LPS-stimulated microglia cells having IC50 values of 60.92 ± 3.45, 56.38 ± 1.05, and 23.94 ± 1.08 µg/mL, respectively. Kinetic studies showed that the tyrosinase inhibitory activity of artonin E is via a noncompetitive inhibition mechanism. Further, artolankanin A and artobiloxanthone exhibited good A5-lipoxygenase enzyme inhibitory activity having IC50 values of 59.48 ± 1.06 and 62.45 ± 2.25 µg/mL, respectively. Insights from molecular docking and molecular dynamics simulations align with these experimental observations and propose plausible mechanisms of inhibition. Collectively these results suggest that these compounds have the potential to be used as depigmenting and anti-inflammatory agents.