Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O-methylhonokiol in zymosan-induced animal models

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Title
Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O-methylhonokiol in zymosan-induced animal models
Author(s)
H S Kim; H S Ryu; J S Kim; Y G Kim; H K Lee; J K Jung; Y S Kwak; K Lee; S Y Seo; Ji Eun Yun; Jong Soon Kang; J T Hong; Y Kim; S B Han
Bibliographic Citation
Archives of Pharmacal Research, vol. 38, no. 5, pp. 813-825
Publication Year
2015
Abstract
4-O-methylhonokiol (MH) is known to inhibit inflammation by partially understood mechanisms. Here, the anti-inflammatory mechanisms of MH were examined using enzymatic, cellular, and animal assays. In enzymatic assays, MH inhibited COX-2 activity with an IC50 of 0.062 μM, and also COX-1 with an IC50 of 2.4 μM. In cellular assays, MH was immunotoxic above 10 μM. At non-toxic concentrations (below 3 μM), MH strongly inhibited COX-2-mediated prostaglandin production with an IC50 of 0.1 μM, whereas did not or slightly affect other functions of B cells, T cells, dendritic cells, and macrophages. In an animal model, MH inhibited the increase in footpad thickness and popliteal lymph node weight in zymosan-injected mice. When analyzed the draining pLNs of zymosan-injected mice on day 5, MH inhibited the overall inflammatory responses. However, MH inhibited cyclooxygenase (COX)-2-mediated prostaglandin production without affecting tumor necrosis factor-α production in inflamed tissues within 6 h after zymosan injection. In summary, our data suggest that COX-2 may be a direct anti-inflammatory target of MH in vitro and in vivo.
Keyword
4-O-methylhonokiolAnti-inflammatory targetCyclooxygenase-2
ISSN
0253-6269
Publisher
Pharmaceutical Soc Korea
DOI
http://dx.doi.org/10.1007/s12272-014-0456-8
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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