Discovery of cyclooxygenase inhibitors from medicinal plants used to treat inflammation.
Eleven authenticated botanicals used in the traditional Chinese medicine Huo-Luo-Xiao-Ling Dan were screened for ligands to cyclooxygenase (COX) using pulsed ultrafiltration liquid chromatography-mass spectrometry, and a mass spectrometry-based enzyme assay was used to determine the concentration of each of 17 ligands that inhibited COX-1 or COX-2 by 50% (IC(50)). Acetyl-11-keto-beta-boswellic acid, beta-boswellic acid, acetyl-alpha-boswellic acid, acetyl-beta-boswellic acid, and betulinic acid were COX-1 selective inhibitors with IC(50) values of approximately 10 microM. Senkyunolide O and cryptotanshinone were COX-2 selective inhibitors with IC(50) values of 5 microM and 22 microM, respectively. Roburic acid and phenethyl-trans-ferulate inhibited COX-1 and COX-2 equally. COX inhibition and the IC(50) values of most of these natural product ligands have not been reported previously.
Cao
Hongmei
H
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, IL, USA.
Yu
Rui
R
Choi
Yongsoo
Y
Ma
Zhong-Ze
ZZ
Zhang
Hongjie
H
Xiang
Wei
W
Lee
David Yue-Wei
DY
Berman
Brian M
BM
Moudgil
Kamal D
KD
Fong
Harry H S
HH
van Breemen
Richard B
RB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; C547651:huo luo xiao ling dan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2