Zerumbone-induced antinociception: involvement of the L-arginine-nitric oxide-cGMP -PKC-K+ ATP channel pathways.
This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception.
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Enoch Kumar
EK
Perimal
Muhammad Nadeem
MN
Akhtar
Azam Shah
AS
Mohamad
Mohd Hanief
MH
Khalid
Ong Hui
OH
Ming
Syamimi
S
Khalid
Lee Ming
LM
Tatt
Mohd Nasier
MN
Kamaldin
Zainul Amiruddin
ZA
Zakaria
Daud Ahmad
DA
Israf
Nordin
N
Lajis
Mohd Roslan
MR
Sulaiman
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010147:Pain Measurement; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D000700:Analgesics; D054086:KATP Channels; D026902:Potassium Channel Blockers; D043782:Receptor, Bradykinin B2; D012717:Sesquiterpenes; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D009569:Nitric Oxide; C403304:zerumbone; D001120:Arginine; D011493:Protein Kinase C; D006152:Cyclic GMP