Oligostilbenes isolated from Gnetum latifolium Blume and their inhibitory potential to neuro-inflammation

Oligostilbenes are polyphenolic compounds commonly found in the Gnetum genus. Many scientists are interested in such structures owing to their complicated linkage and biological activity [1]. Gnetum genus has been widely used with a long history as folk medicine for such pathological symptoms as bronchitis, arthritis, and asthma [2,3]. Based on the inhibitory action on nitric oxide (NO) production induced by transfection with construct expressing amyloid beta₄₂ (Aβ₄₂), new oligostilbenes (compounds 1, 10, 12 and 13) along with nine known compounds were isolated from ethyl acetate soluble fraction of Gnetum latifolium (G. latifolium) and identified. Chemical structures of nine known compounds were determined as gnetifolin F (2), (+)-E-viniferin (3), parvifolol C (4), lehmbachol B (5), gnetijolin C (6), cis-shegansu B (7), trans-shegansu B (8), gnetin H (9), latifolol (11) respectively. The chemical structures of new compounds were elucidated by the extensive NMR spectrum analyses (¹H-NMR, ¹³C-NMR, HMBC, HMQC, COSY, and ROESY). For the absolute structures of four new oligostilbenes, most probable stereochemical structures by Chem3D molecular modelling were proposed through further NMR analysis. These structures were subsequently confirmed by the comparison of those of ECD calculations and the experimental CD spectrum. The anti-inflammatory responses of isolated thirteen compounds were evaluated to the secreted NO concentration induced by transfection with plasmids expressing Aβ₄₂ gene in BV-2 cell line. Among the tested compounds, compound 3, 7 and 11 dramatically inhibited NO production. The value was 2.7, 2.1 and 0.8µM in NO production treated by compound 3, 7, and 11 respectively, these data indicate strong inhibitory activities on neuro-inflammatory responses compared to 6.9µM in the amyloid beta₄₂-treated cells. Further, the results suggest the structure of these oligostilbenes have merits to study on new therapeutic strategies for neurodegenerative diseases such as Alzheimer's disease.

Keywords: oligostilbene, Gnetum latifolium Blume, BV-2 cell, Aβ₄₂, neuro-inflammation.

References:

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