Quercetin: further investigation of its antinociceptive properties and mechanisms of action.
The antinociceptive action of quercetin, a common bioactive flavonoid present in many medicinal plants, was assessed in different models of chemical and thermal nociception in mice. Quercetin (10-60 mg/kg, i.p. or 100-500 mg/kg, p.o.) dose-dependently inhibited nociceptive behavior in the acetic acid-induced pain test. Moreover, quercetin (10-60 mg/kg, i.p.) inhibited both phases of formalin-induced pain, with ID50 values of 374.1 (68.0-402.0) mmol/kg and 103.0 (45.0-201.0) mmol/kg, for the neurogenic and inflammatory phases, respectively. Quercetin (10-60 mg/kg) also inhibited the nociception induced by glutamate and capsaicin by 68.2% and 75.5%, respectively. Its analgesic action was significantly reversed by p-chlorophenylalanine methyl ester, katanserin, methysergide, a GABA(A) antagonist (bicuculline), or a GABA(B) antagonists (baclofen). Its action was also modulated by tachykinins, but was not affected by adrenal-gland hormones. Furthermore, the antinociceptive effects did not result from muscle-relaxant or sedative action. Together, these results indicate that quercetin produces dose-related anti-nociception in several models of chemical pain, through mechanisms that involve interaction with L-arginine-nitric oxide, serotonin, and GABAergic systems. These results confirm and extend other investigations on the analgesic effect of quercetin and its mechanisms of action.
Filho
Arnaldo Willain
AW
Programa de Mestrado em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR)/CCS, Universidade do Vale do Itajaí (UNIVALI), 88302-202, Itajaí, SC, Brazil.
Filho
Valdir Cechinel
VC
Olinger
Leonardo
L
de Souza
Márcia Maria
MM
D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin; D018678:Cholinergic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde; D018682:GABA Agents / Q000494:pharmacology; D018698:Glutamic Acid; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000700:Analgesics; D000701:Analgesics, Opioid; D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D018682:GABA Agents; D012702:Serotonin Antagonists; D005557:Formaldehyde; D018698:Glutamic Acid; D011794:Quercetin; D019001:Nitric Oxide Synthase; D019342:Acetic Acid; D002211:Capsaicin