New benzenoids and anti-inflammatory constituents from the stem wood of Zanthoxylum nitidum

Abstract

Zanthoxylum nitidum (Rutaceae) is a scandent shrub, distributed from India to North Australia and Southeast China [1]. Alkaloids, lignans, flavonoids, and their derivatives were isolated from this plant in previous studies. Many of these compounds were found to exhibit significant bioactivities. Investigation of EtOAc-soluble fraction of the stem wood of Z. nitidum has led to the isolation of three new benzenoids, (E)-4-(4-hydroxy-3-methylbut-2-enyloxy)benzaldehyde (1), (E)-methyl 3-(4-((E)-4-hydroxy-3-methylbut-2-enyloxy)phenyl)acrylate (2), and (Z)-methyl 3-(4-((E)-4-hydroxy-3-methylbut-2-enyloxy)phenyl)acrylate (3), together with seventeen known compounds. The structures of new compounds 1-3 were determined through spectral analyses including extensive 2D NMR data. The anti-inflammatory effects of compounds isolated from the stem wood of Z. nitidum were evaluated by suppressing fMet-Leu-Phe/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release by human neutrophils. Diphenyleneiodonium and phenylmethylsulfonyl fluoride were used as positive controls for superoxide anion generation and elastase release, respectively. From the results of our anti-inflammatory tests, the following conclusions can be drawn: (a) (S)-6-Acetonyl-8-O-demethyldihydrochelerythrine, decarine, (+)-episesamin, (–)-sesamin, and N-methylflindersine exhibited potent inhibitory activities (IC50≤4.69µg/mL) on human neutrophil superoxide anion generation. (b) Decarine, (+)-episesamin, (–)-sesamin, and N-methylflindersine exhibited potent inhibition (IC50≤2.56µg/mL) against fMLP-induced elastase release. (c) N-Methylflindersine was the most effective among the isolated compounds, with IC50 values of 0.35 and 0.41µg/mL, respectively, against fMLP-induced superoxide anion generation and elastase release.