Suppression of TRPV1 and P2Y nociceptors by honokiol isolated from Magnolia officinalis in 3rd degree burn mice by inhibiting inflammatory mediators

Abstract

Burn pain is one of the worst imaginable pain, associated with considerable morbidity and mortality worldwide. The management of pain made significant progress; however, more research is needed for burn pain. In the present study, the antinociceptive effect of honokiol extracted from Magnolia officinalis was assessed for 3 consecutive days. The third-degree burns were induced by the hot water method. The honokiol both by intraperitoneal (i.p) and intra plantar (i.pl) route and in combination with tramadol (i.p) was found to be effective in significantly reducing the mechanical allodynia, hyperalgesia, thermal hyperalgesia and paw edema. Honokiol also succeeded in reducing weight loss and spontaneous pain behavior in mice. Honokiol treatment both i.p and ipl decrease significantly the loss of total protein (3.3 and 3.4 g/dl of total protein) and albumin (2.2 and 2.6 g/dl of total albumin) respectively. It also significantly recovers the normal balance of blood electrolytes and normalizes blood profile. Effect of honokiol on cytokines and mRNA expression levels of TRPV1 and P2Y were also assessed. Honokiol significantly decreases the expression of TNF-α, IL-1β and IL-6 and decreases expression level of TRPV1 and P2Y. Additionally, TRPV1 and P2Y proteins expression levels were also assessed by Western blot in paw skin tissue, sciatic nerve and spinal cord which were remarkably down-regulated by honokiol. Histological analysis of vehicle control and drug-treated paws were also performed through hematoxylin and eosin (H&E) staining which exhibited that honokiol significantly reduced the dermal layers distortion and inflammation associated with the burn. The antioxidant enzymes and nitric oxide (NO) were also determined through ELISA. Honokiol treatment also potentiates the expression of reduced glutathione and glutathione S-transferase, and catalase levels and reduced significantly the nitric oxide (NO) as compared to the burn-induced group. It can be concluded on the base of the results that honokiol has a significant analgesic activity through its action on cytokines and by downregulating TRPV1 and P2Y receptors. It also has a protective role against burn damage by upregulation of antioxidants.

Keywords: Allodynia; Burn; Honokiol; Hyperalgesia; TRPV1 and P2Y.