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Biomed Pharmacother. 2018 Feb;98:609-618. doi: 10.1016/j.biopha.2017.12.102. Epub 2018 Jan 4.

Antinociceptive, anti-inflammatory and toxicological evaluation of semi-synthetic molecules obtained from a benzyl-isothiocyanate isolated from Moringa oleifera Lam. in a temporomandibular joint inflammatory hypernociception model in rats.

Author information

1
Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: alain3iverson@hotmail.com.
2
North-Eastern Biotechnology Network, Federal University of Pernambuco, Avenida Professor Moraes Rego, 1235 Cidade Universitária, 50670-901 Recife, Pernambuco, Brazil. Electronic address: danielleval@hotmail.com.
3
Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: felipedsilveira@gmail.com.
4
Faculty of Dentistry, Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: ffer9352@uni.sydney.edu.au.
5
Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: hermanycf@gmail.com.
6
Faculty of Dentistry, Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: ellenjbe@hotmail.com.
7
Department of Organic and Inorganic Chemistry, Federal University of Ceara, Campus Pici. Av. Humberto Monte, 2825 - Pici, 60.440-593 Fortaleza, Ceará, Brazil. Electronic address: dianakelly25@hotmail.com.
8
Faculty of Dentistry, Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: igoriuco@gmail.com.
9
Department of Organic and Inorganic Chemistry, Federal University of Ceara, Campus Pici. Av. Humberto Monte, 2825 - Pici, 60.440-593 Fortaleza, Ceará, Brazil. Electronic address: fgerhar@gmail.com.
10
Department of Organic and Inorganic Chemistry, Federal University of Ceara, Campus Pici. Av. Humberto Monte, 2825 - Pici, 60.440-593 Fortaleza, Ceará, Brazil. Electronic address: jmafez@ufc.br.
11
Department of Organic and Inorganic Chemistry, Federal University of Ceara, Campus Pici. Av. Humberto Monte, 2825 - Pici, 60.440-593 Fortaleza, Ceará, Brazil. Electronic address: reisilva_ce@yahoo.com.br.
12
Department of Morphology, Federal University of Ceara - Campus Porangabussu, Rua Delmiro de Farias, s/n - Rodolfo Teófilo, 60.430-170 Fortaleza, Ceará, Brazil. Electronic address: gerlybrito@hotmail.com.
13
Faculty of Medicine and Dentistry São Leopold Mandic, Rua Doutor José Rocha Junqueira, 13, Ponte Preta, 13045-755 Campinas, SP, Brazil. Electronic address: juliana.napimoga@slmandic.edu.br.
14
Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: pintovicente@gmail.com.
15
Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: gcristino@gmail.com.
16
Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: mirnabrayner@gmail.com.
17
Faculty of Dentistry, Federal University of Ceara, Avenida Comandante Maurocélio Rocha Pontes, 100 Derby, 62.042-280 Sobral, Ceará, Brazil. Electronic address: helliadachaves@yahoo.com.br.

Abstract

Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1 μg/kg; MC-D1 1 μg/kg, MC-D3 100 μg/kg, MC-D6 1 μg/kg, MC-D7 1 μg/kg, MC-D8 1 μg/kg, MC-D9 10 μg/kg, and MC-H 1 μg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50 μL) and serotonin (255 mg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action.

KEYWORDS:

Hypernociception; Isothyocianates; Moringa oleifera; Temporomandibular joint; Toxicity

PMID:
29289835
DOI:
10.1016/j.biopha.2017.12.102
[Indexed for MEDLINE]

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