Assessment of Mechanisms Involved in Antinociception Caused by Myrsinoic Acid B

Abstract

Considerable efforts have recently been made to discover new analgesic and antiinflammatory agents with increased efficacy and improved side effect profiles. In this context, the compounds obtained from medicinal plants have been extensively studied.1,2) Prenylated aromatic compounds isolated from plant sources are common in the literature, including some that are diprenylated benzoic acids. This class of compounds is present in Rapanea genus and has been demonstrated to have anti-inflammatory activity, 3) then the compound 5-carboxy-2,3-dihydro-2-(1Ј,5Ј-dimethyl-1Ј-hydroxy-4Ј-hexenyl)-7-(3Љ-methyl-2Љ-butenyl) benzofuran, also known as myrsinoic acid B (AMB) (Fig. 1) was chosen in this study. It was first isolated as methyl ester from Rapanea umbellatta 4) and was also reported in R. lancifolia, R. guaianensis, 5) R. Myricoides 6) and R. Seguinii.3) So far only antiinflammatory and methioninase inhibitory activities have been reported for this compound.3,7) We have previously verified that AMB, isolated from the bark of CHCl 3 extract of Rapanea ferruginea, exhibits significant and potent antinociceptive action when evaluated in some pharmacological models of pain in mice. 8) In this study, we investigated some of the possible mechanisms, underlying the antinociceptive action of AMB. Extraction and Isolation of AMB Bark of Rapanea ferruginea (600 g) was dried at 40°C for 2 d, powdered and successively extracted by maceration with CHCl 3 for 7 d at room temperature. The extract was concentrated under reduced pressure, to yield residues (70.2 g). The CHCl 3 extract (60 g) was chromatographed in a silica-gel column with hexane/ ethyl acetate. The fraction eluted with 40% ethyl-acetate in hexane to give impure AMB. This fraction (8.5 g) was rechromatographed in a silica-gel column and with 30% ethyl-acetate in hexane give pure AMB (4.3 g). MATERIALS AND METHODS Plant Material

Structural and physicochemical characterization and purity assessment of myrsinoic acids A and B, active compounds isolated from Rapanea ferruginea barks

“…Isolation procedures were performed according to Hess et al (2010) and Bella-Cruz et al (2013) as briefly described below: a mixture of hydroethanolic extracts of stem bark, branches and leaves of R. ferruginea (43 g) was subjected to silica gel column chromatography with hexane/ethyl acetate to obtain myrsinoic acids A and B in their pure forms. The fractions eluted with 20% and 40% of ethyl-acetate in hexane gave MAA (2.3 g), and MAB (4.2 g), respectively.…”

“…1B exhibited methioninase inhibitor activity from periodontal bacteria such as Fusobacterium nucleantum, Porphyromonas gingivalis and Treponema denticola (Ito et al, 2008). In addition, this compound showed a significant antinociceptive effect through mechanisms that involve interaction with L-arginine-nitric oxide, the serotonergic and cholinergic systems, and the aadrenoceptors (Hess et al, 2010). MAB administered preventively or therapeutically, systemically or by the spinal route, reduced mechanical and thermal hypersensitivity in mice submitted to models of inflammatory and neuropathic pain, shows an excellent potential to treat persistent pain in humans, without any significant side effects (Antonialli et al, 2012).…”

Antinociceptive effect of Lafoensia pacari A. St.-Hil. independent of anti-inflammatory activity of ellagic acid

“…This test also evaluated the involvement of opioids receptors in the analgesic activity of PEtExt. Pre-treatment with naloxone, a non-selective opioid antagonist [36], refutes the involvement of these receptors in the mechanism of analgesic action of PEtExt. These results reinforce the hypothesis that this plant is endowed with important antinociceptive effects independent of the anti-inflammatory activity.…”

Nanoemulsion as a carrier to improve the topical anti-inflammatory activity of stem bark extract of <em>Rapanea ferruginea</em>

“…22 In previous studies by our research group, R. ferruginea and markers myrsinoic acids A and B (MAA and MAB) showed antiinflammatory and analgesic effects when administered through oral and intravenous routes. [22][23][24] Although other studies have shown that myrsinoic acids isolated from Myrsine species have anti-inflammatory activities, 25,26 there are no reports about the topical anti-inflammatory activity of R. ferruginea extracts.…”