Neolignans, a coumarinolignan, lignan ferivatives, and a chromene: Anti-inflammatory constituents from Zanthoxylum avicennae

Zanthoxylum avicennae (Lam.) DC (Rutaceae) is an evergreen shrub distributed in Vietnam, Philippines, southern

China, and Taiwan [1]. A decoction of its stems is used as a stomach tonic and as a counter-poison to snake bite [2].

In our studies on the anti-inflammatory constituents of Formosan plants, many species have been screened for in vitro anti-inflammatory activity, and Z. avicennae has been found to be one of the active species. Investigation of the EtOAc-soluble fraction of the stem wood of Z. avicennae has led to the isolation of eight new compounds, including four new neolignans, (7′S,8′S)-5-demethoxybilagrewin (1), (7′S,8′S)-5-O-demethyl-4′-O-methylbilagrewin (2), (7′S,8′S)-nocomtal (3), and (7′S,8′S)-bilagrewin (4), a new coumarinolignan, (7′S,8′S)-4′-O-methylcleomiscosin D (5), two new lignan derivatives, (+)-9′-O-cis-feruloyl-5,5′-dimethoxylariciresinol (6) and (+)-9′-O-trans-feruloyl-5,5′-dimethoxylariciresinol (7), and a new chromene, (E)-3-(2,2-dimethyl-2H-chromen-6-yl)acrylaldehyde (8), together with 18 known compounds (9–26). The structures of these new compounds were determined through in-depth spectroscopic and MS analyses. Among the isolated compounds, (7′S,8′S)-4′-O-methylcleomiscosin D (5), cleomiscosin D (9), skimmianine (18), robustine (19), and integrifoliolin (23) exhibited inhibition (IC₅₀≤18.19µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (FMLP/CB). In addition, skimmianine (18) inhibited FMLP/CB-induced elastase release with an IC₅₀ value of 19.15±0.66µM.

Acknowledgement: This work was supported by grant from the National Science Council of the Republic of China.

References: 1. Ho, T. C. (2007) Endemic Species Res. 9: 29–52.

2. Perry, L. M. (1980) Medicinal Plants of East and Southeast Asia: Attributed Properties and Uses, The MIT Press, Cambridge, p 370.