Mecanismos periféricos e centrais dos efeitos antinociceptivo e anti-inflamatórios de dois compostos semissintéticos mc-d7 e mc d9 obtidos a partir de flores da moringa oleifera na atm de ratos

Abstract

Temporomandibular joint (TMJ) dysfunctions can cause painful and limiting conditions in the quality of life. The mechanisms involved in this clinical condition, however, are still not fully understood, and the established therapy is not completely effective. The Moringa oleifera plant has several therapeutic applications, among them antinociceptive and anti-inflammatory effects. The objective of this study was to evaluate the antinociceptive and anti-inflammatory efficacy and the central and peripheral mechanisms of two semi-synthetic compounds obtained from a benzylisothiocyanate, MC-1 secondary metabolite, isolated from Moringa oleifera flowers (MC-D7 and MC-D9) in the TMJ of rats. Male Wistar rats (180-240 g) were used in which groups were treated with saline solution (0.9%), MC-D7 (0.01, 0.1, 1 μg/kg) or MC-D9 (0, 01; 0.1; 1ηg / kg) orally. After 60 minutes, intra-articular (i.a.) saline solution (50 μL, 0.9%) was applied in the control or formalin group (50 μL, 1.5%) in the left TMJ. The nociceptive response was measured by quantifying, in seconds, the act of the mouse scratching the left TMJ region and by the number of times to raise the head reflexively over the 45 minute period. Afterwards the animals were euthanized and the periarticular tissues (TPA), trigeminal ganglion (GT) and caudal subnucleus (SC) on the left side were removed. We investigated the involvement of cannabinoid (CB) receptors through CB1 (AM281) or CB2 (AM630) receptor antagonists. A study of vascular permeability with Evans Blue, IL -1β and IL-8 cytokines in TPA and GT by ELISA, analysis of the expression of ICAM-1 and CD55 adhesion molecules in TPA, and of P2X7 and NF-Қβ in SC by Western Blotting (WB). The MC-D7 and MC-D9 compounds showed antinociceptive and antiinflammatory effects by reducing behavioral nociceptive response, plasma extravasation with Evans Blue in TPA, reduction of IL-1β and IL-8 cytokine dosages in TPA and in GT, the reduction of the ICAM and CD55 adhesion molecules in the TPA, and the reduction P2X7 and NF-Қβ and SC, without involvement with cannabinoid receptors. The compounds MC-D7 and MC-D9 therefore present antinociceptive and anti-inflammatory activity by peripheral and central pathways