-Acetyldopamine dimers from attenuates lipopolysaccharides induced inflammation and inhibits cathepsin C activity.

(rice field grasshopper) is an edible insect with numerous health beneficial properties, traditionally being used to treat many ailments in Korea and other countries. has been used from centuries, however, a little is known about the chemical functionality of its bioactive compounds. Therefore, this study examined the anti-inflammatory and cathepsin C inhibitory activities of -acetyldopamine dimer (2R, 3S)-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(-acetyl-2″-aminoethyl)-1,4-benzodioxane (DAB1) isolated from . Results showed that DAB1 reduced the expression of pro-inflammatory mediator (iNOS, COX-2) and cytokines (TNF-α, IL-1β, and IL-6), and curtailed the nuclear translocation of NF-κB by inhibiting the phosphorylation of IκBα in lipopolysaccharide stimulated macrophages. Additionally, DAB1 inhibited cathepsin C activity at the cellular level, supported by assay (Ki, 71.56 ± 10.21 µM and Kis, 133.55 ± 18.2 µM). Moreover, combinatorial molecular simulation and binding free energy analysis suggested a significant stability and binding affinity of cathepsin C-DAB1 complex via formation of hydrogen bond and hydrophobic interactions with the catalytic residues (Gln228, Thr379, Asn380, and Hie381). Also, essential dynamics analysis showed DAB1 induced non-functional motions in cathepsin C structure. Collectively, DAB1 was concluded as anti-inflammatory and cathepsin C inhibiting agent and could be used in the drug development against respective diseases.