Anti-inflammatory activity of 4,4'-dihydroxy-alpha-truxillic acid.
The oral anti-inflammatory activity of 4,4'-dihydroxy-alpha-truxillic acid (1) was compared with that of two other nonsteroidal anti-inflammatory drugs, loxoprofen sodium (LOX) and diclofenac sodium (DIC). The activity of 1 against the inflammatory pain response induced by formalin was comparable to that of LOX, but weaker than that of DIC. In the monosodium urate (MSU)-induced acute inflammatory model, 1 showed stronger anti-inflammatory activity than both LOX and DIC. The ED50 value for 1 was 4.5 micromol/kg, while the values for LOX and DIC were 65 and 25 micromol/kg, respectively. Otherwise, the oral single-dose toxicity of 1 was investigated in both sexes of Sprague-Dawley rats administered once at a dose of 2000 mg/kg. 1 showed no death, clinical signs, changes in body weight or pathological findings related to the treatment. In addition, no mutagenicity was observed in the reverse mutation assay. Furthermore, 1 did not show any ulcerogenic activity at doses ranging from 30 to 300 mg/kg in rat. Thus, 1 might be considered to be an effective anti-inflammatory agent with no deleterious adverse effect.
Chi
Yu-Ming
YM
Seiwa Pharmaceutical Ltd., Kitaibaraki, Ibaraki, Japan. chi-59@unimatec.co.jp
Nakamura
Motoyuki
M
Zhao
Xi-Ying
XY
Yoshizawa
Toyokichi
T
Yan
Wen-Mei
WM
Hashimoto
Fumio
F
Kinjo
Junei
J
Nohara
Toshihiro
T
Sakurada
Shinobu
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D003503:Cyclobutanes / Q000494:pharmacology* / Q000633:toxicity; D004008:Diclofenac / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005557:Formaldehyde; D007213:Indomethacin / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D009152:Mutagenicity Tests; D010147:Pain Measurement / Q000187:drug effects; D010666:Phenylpropionates / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D014527:Uric Acid
C510228:4,4'-dihydroxy-alpha-truxillic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003503:Cyclobutanes; D010666:Phenylpropionates; D004008:Diclofenac; D005557:Formaldehyde; D014527:Uric Acid; C040656:loxoprofen; D007213:Indomethacin