Myricitrin Derivatives: In Vivo Evaluation of Analgesic Activity in Inflammatory Pain Models

Inflammatory pain arises from the activation of a complex molecular cascade involving the release of pro-inflammatory mediators and sensitization and activation of nociceptors. Although acute pain is protective, persistent pain associated with ongoing inflammation can occur in disabling conditions such as osteoarthritis (OA). Prolonged use of anti-inflammatory drugs is associated with adverse effects, reinforcing the need for new alternatives. Myricitrin, a glycosylated flavonoid with analgesic and anti-inflammatory properties, is a potential alternative; however, its oral administration is limited by low lipophilicity and intestinal absorption. Thus, acylated myricitrin derivatives were synthesized by biocatalysis from myricitrin and nine vinyl esters (C3–C18) using Novozym® 435 for evaluation in murine models of inflammatory pain. Myricitrin was first tested in the carrageenan (CAR)-induced paw inflammation model to assess its suitability for screening these derivatives. For in vivo evaluation, 1% CAR was injected into the mouse hind paw; edema was measured using a digital caliper, and thermal hyperalgesia assessed using the hot plate test. Myricitrin or vehicle was administered 1 h before CAR. CAR injection induced paw edema and thermal hyperalgesia from 1 to 72 h. Preliminary results showed that myricitrin (30 mg/kg p.o. or i.p.) increased paw withdrawal latency in the hot plate test compared with vehicle, with a more pronounced effect following i.p. administration. At 100 mg/kg, i.p. administration showed a similar temporal profile but a greater effect than 30 mg/kg, whereas p.o. administration was less effective than the lower dose. None of the treatments significantly reduced CAR-induced paw edema. These findings confirm the antinociceptive effect of myricitrin and support the use of the CAR model for screening its acylated derivatives, which will subsequently be evaluated in an OA model.

Biochem. Pharmacol. (2006) 72:1707.

Biochem. Pharmacol. (2007) 74:924.