Antinociceptive compounds and LC-DAD-ESIMSn profile from Dictyoloma vandellianum leaves.

Lucas Silva Abreu,Yuri Mangueira Do Nascimento,Maria Lenise Silva Guedes,Mireille Le Hyaric,Josean Fechine Tavares,Gisele Graça Leite Dos Santos,Eudes Da Silva Velozo,César Augusto Gonçalves Dantas,Cristiane Flora Villarreal,Renan Fernandes Do Espírito Santo,Iura Muniz Alves,Marcelo Sobral Da Silva,Branislav T Šiler

doi:10.1371/journal.pone.0224575

Abstract

Limonoids, quinolone alkaloids and chromones have been reported as constituents of Dictyoloma vandellianum Adr. Juss. (Rutaceae). Although those compounds are known for their biological activities, only the anti-inflammatory activity of chromones isolated from the underground parts has been evaluated. There are no studies of the pharmacological properties of the aerial parts of D. vandellianum. The present study was carried out to determine the phytochemical profile and antinociceptive activity of the methanol extract, fractions and isolated compounds of leaves of D. vandellianum. The phytochemical profile was performed by HLPC-DAD-ESIMSn and pure substances obtained were characterized by MS and NMR spectroscopy. The antinociceptive activity was assessed using the formalin assay in mice, and the motor function in the rotarod test. ME and all the fractions obtained from ME produced antinociceptive effects. Among them, the ethyl ether fraction was the most active. Data from HPLC-DAD-ESIMSn showed that the ethyl ether fraction presented 42 compounds. The major compounds isolated from this fraction—gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose–were tested and produced antinociceptive effects. Gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose at antinociceptive doses did not affect the motor performance in mice in the rotarod test. This work is the first report of the occurrence of gallotanins in D. vandellianum. In addition, the pharmacological study showed that D. vandellianum leaves present antinociceptive activity, probably induced by gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-d-glucopyranose.

Highlights

Pain is an unpleasant sensation that affects 20% of adults worldwide and it is associated with a wide range of diseases and tissue damage [1]
The isolated compounds were identified as gallic acid, methyl gallate and 1,2,6-tri-O-galloyl-β-Dglucopyranose
The present study demonstrates that systemic administration of methanol extract of D. vandellianum leaves produces a consistent antinociceptive effect

Summary

Methods

Nuclear magnetic resonance 1H and 13C (single and two-dimensional) spectra were obtained on Varian spectrometer, model Gemini-500 (Varian, Inc., Palo Alto, CA, USA) (1H: 500 MHz and 13C: 125 MHz); using CD3OH solvent and TMS as internal standard. All chromatographic separations were performed on octadecyl-functionalized 200–400 mesh (Sigma-Aldrich), using opened columns (40 × 4.5 cm, 45 × 5 cm, 15 × 8 cm). Thin-layer chromatography (TLC) was performed on glass plates covered with silica gel PF254 Merck 60 and revealed with iodine vapor and/or UV light (254 and 365 nm). Indomethacin and dimethyl sulfoxide were obtained from Sigma Chemical Company (St. Louis, MO, USA). Indomethacin was dissolved in Tris HCl 0.1 M pH 8.0 plus saline. The chloroform fractions were dissolved in 5% DMSO plus saline, and the remaining fractions and compounds were dissolved directly in saline

Results

Discussion

Conclusion