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.
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.
Arnaldo Willain
AW
Filho
Valdir Cechinel
VC
Filho
Leonardo
L
Olinger
Márcia Maria
MM
de Souza
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