Suppressive effect of the herbal medicine Oren-gedoku-to on cyclooxygenase-2 activity and azoxymethane-induced aberrant crypt foci development in rats.
The present study is part of a program to obtain effective chemopreventive agents with low toxicity from medicinal herbs and traditional herbal medicines. We previously reported that Oren (Coptidis rhizoma) and Ogon (Scutellariae radix) inhibit azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation. In the present investigation, we found Sanshishi (Gardeniae fructus) and the traditional herbal medicine Oren-gedoku-to (OGT), composed of Ogon, Oren, Sanshishi and Obaku, also have preventive potential. Sanshishi and OGT decreased the numbers of ACF to 25.2 and 59.4% of the control value at 2% in the diet, respectively. Adverse effects, evidenced by body weight loss, were weaker with OGT than component herbs. To investigate their mechanisms of action, the influence on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities was studied. Both OGT and Sanshishi inhibited COX-2 but not COX-1, this presumably contributing to their suppressive effects on ACF development. The results suggest that OGT may be useful for colon cancer chemoprevention in terms of efficacy and toxicity.
Fukutake
M
M
Kampo & Pharmacognosy Laboratory, R & D Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, Japan. fukutake_musato@mail.tsumura.co.jp
Miura
N
N
Yamamoto
M
M
Fukuda
K
K
Iijima
O
O
Ishikawa
H
H
Kubo
M
M
Okada
M
M
Komatsu
Y
Y
Sasaki
H
H
Wakabayashi
K
K
Ishige
A
A
Amagaya
S
S
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use* / Q000633:toxicity; D001397:Azoxymethane / Q000037:antagonists & inhibitors; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use* / Q000633:toxicity; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D010936:Plant Extracts / Q000627:therapeutic use / Q000633:toxicity; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D008565:Membrane Proteins; D010936:Plant Extracts; C061676:oren gedoku to; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D001397:Azoxymethane