title: Validation of cyclooxygenase-2 as a direct anti-inflammatory target of 4-O-methylhonokiol in zymosan-induced animal models.
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.
authors: College of Pharmacy, Chungbuk National University, 52 Naesoodong, Heungduk, Cheongju, Chungbuk, 361-763, South Korea.
authors: Hyung Sook
authors: HS
authors: Kim
authors: Hwa Sun
authors: HS
authors: Ryu
authors: Ji Sung
authors: JS
authors: Kim
authors: Yong Guk
authors: YG
authors: Kim
authors: Hong Kyung
authors: HK
authors: Lee
authors: Jae Kyung
authors: JK
authors: Jung
authors: Young Shin
authors: YS
authors: Kwak
authors: Kiho
authors: K
authors: Lee
authors: Seung Yong
authors: SY
authors: Seo
authors: Jieun
authors: J
authors: Yun
authors: Jong Soon
authors: JS
authors: Kang
authors: Jin Tae
authors: JT
authors: Hong
authors: Youngsoo
authors: Y
authors: Kim
authors: Sang-Bae
authors: SB
authors: Han
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology; D017705:Lignans / Q000008:administration & dosage / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015054:Zymosan / Q000633:toxicity*
chemical_list: C542058:4-O-methylhonokiol; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D017705:Lignans; D015054:Zymosan; D051546:Cyclooxygenase 2