Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice.
The antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, were examined in mice. The p.o. administration of N. sativa oil (50-400 mg/kg) dose-dependently suppressed the nociceptive response in the hot-plate test, tail-pinch test, acetic acid-induced writhing test and in the early phase of the formalin test. The systemic administration (2.5-10 mg/kg, p.o. and 1-6 mg/kg, i.p.) and the i.c.v. injection (1-4 microgram/mouse) of thymoquinone attenuated the nociceptive response in not only the early phase but also the late phase of the formalin test. Naloxone injected s.c. (1 mg/kg) significantly blocked N. sativa oil- and thymoquinone-induced antinociception in the early phase of the formalin test. Moreover, the i.c.v. injection of naloxone (10 microgram/mouse), the mu(1)-opioid receptor antagonist, naloxonazine (1-5 microgram/mouse), or the kappa-opioid receptor antagonist, nor-binaltorphimine (1-5 microgram/mouse), significantly reversed thymoquinone-induced antinociception in the early phase but not the late phase of the formalin test, whereas the delta-opioid receptor antagonist, naltrindole (1-5 ng/mouse, i.c.v.), had no effect on either phase. The antinociceptive effect of morphine was significantly reduced in thymoquinone- and N. sativa oil-tolerant mice, but not vice versa. These results suggest that N. sativa oil and thymoquinone produce antinociceptive effects through indirect activation of the supraspinal mu(1)- and kappa-opioid receptor subtypes.
Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, 930-0194, Toyama, Japan.
A M
AM
Abdel-Fattah
K
K
Matsumoto
H
H
Watanabe
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010938:Plant Oils / Q000494:pharmacology*; D010946:Plants, Medicinal
D018712:Analgesics, Non-Narcotic; D016227:Benzoquinones; D010938:Plant Oils; D009270:Naloxone; D009271:Naltrexone; C055382:naltrindole; C003466:thymoquinone