Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain.
The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2 (PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered.
Lin
Yi-Ruu
YR
Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan. lin9135104@yahoo.com.tw
Chen
Hwei-Hsien
HH
Lin
Yu-Chin
YC
Ko
Chien-Hsin
CH
Chan
Ming-Huan
MH
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D018683:Excitatory Amino Acid Agents / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000737:chemistry; D010648:Phenylacetates / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
D000700:Analgesics; D000890:Anti-Infective Agents; D001713:Biphenyl Compounds; D015232:Dinoprostone; D018683:Excitatory Amino Acid Agents; D005998:Glycine; D017705:Lignans; D016202:N-Methylaspartate; D010648:Phenylacetates; D016760:Proto-Oncogene Proteins c-fos; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C107349:2-chloro-5-hydroxyphenylglycine; C578936:Grm5 protein, mouse; C005498:magnolol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols