The anti-inflammatory effect of the aqueous fraction from Dacryodes kukachkana extract involves the L-arginine/NO/cGMP pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dacryodes kukachkana or "breu" is found in the Brazilian Amazon rainforest, being this genus widely used in folk medicine for inflammatory conditions. Experimental studies demonstrated that the hydroethanolic extract of D. kukachkana barks (HEDk), containing phenolic compounds, inhibits inflammatory nociception and healing.

AIM OF THE STUDY: To investigate in silico and in vivo the anti-inflammatory mechanisms of the aqueous fraction from D. kukachkana barks (AFDk), along with its phytochemical characterization by UV-vis, FTIR and HPLC-DAD.

MATERIALS AND

METHODS

Mice received per oral (p.o.) HEDk (50-1000 mg/kg) or AFDk (100-500 mg/kg) before paw edema and peritonitis induction with carrageenan, TNF-α, PGE2 or L-arginine to evaluate: edema; hypernociception; leukocyte influx; myeloperoxidase activity (MPO) and nitrite. To search for the pharmacological targets of AFDk, it was performed in silico the possible interaction with its constituents, and in vivo the pharmacological modulation via blockade of NO synthase and guanylate cyclase pathway.

RESULTS

UV-Vis and FTIR analyses revealed the phenolic profile of the extract. HPLC-DAD analysis of AFDk revealed the predominant presence of ellagic acid, quercetin, and rutin. At 500 mg/kg HEDk (3-5 h) and AFDk (2-5 h) inhibited edema (53, 54%), hypernociception (62, 60%) and neutrophil migration (70, 74%) induced by carrageenan. AFDk also inhibited MPO (28%) and nitrite (74%) in peritoneal fluid, and the edema induced by PGE2 (78%), TNF-α (72%) and L-arginine (66%). The antiedematogenic effect of AFDk was impaired by ODQ, but not by L-NAME, in line with the in sílico analysis (PTGS2, NOS, ALOX5).

CONCLUSIONS

the anti-inflammatory effect of AFDK was mediated by PGE2, TNF- α, and L-arginine/NO/cGMP pathway.