An herbal medicine orengedokuto prevents indomethacin-induced enteropathy.
Prostaglandin E2 (PGE2) is a key regulator of gastrointestinal, immunological, and mucosal homeostasis. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the prostaglandin-producing enzyme cyclooxygenases (COXs), and can induce serious complications, such as gastrointestinal damage, with long-term treatment. Orengedokuto (OGT), a Japanese traditional herbal medicine (Kampo medicine), is effective in various animal models of enteropathy. In the present study we examined whether OGT prevents enteropathy induced by NSAIDs in mice. Ulceration in the small intestine was induced with 2 subcutaneous injections of indomethacin (20 mg/kg body weight). Orally administered OGT prevented or reduced lethality, intestinal lesions, bleeding, increased serum nitrate/nitrite levels, and reduction of mucosal PGE2 induced by indomethacin. These beneficial effects of OGT were accompanied by increased production of PGE2 and interleukin 10 by isolated lamina propria mononuclear cells; COX-2 in these cells may be a major source of PGE2 in normal intestines. These findings suggest that OGT could be an effective therapeutic agent for the treatment of inflammatory bowel disease and adverse reactions to NSAIDs.
Miura
Naoko
N
Central Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. miura_naoko@mail.tsumura.co.jp
Fukutake
Masato
M
Yamamoto
Masahiro
M
Ohtake
Nobuhiro
N
Iizuka
Seiichi
S
Imamura
Sachiko
S
Tsuchiya
Naoko
N
Ishimatsu
Makoto
M
Nakamura
Yuichi
Y
Ishige
Atsushi
A
Watanabe
Kenji
K
Kase
Yoshio
Y
Takeda
Shuichi
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D029001:Herbal Medicine; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009578:Nitrobenzenes / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D004365:Drugs, Chinese Herbal; D009578:Nitrobenzenes; D013449:Sulfonamides; C061676:oren gedoku to; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D016753:Interleukin-10; D015232:Dinoprostone; D007213:Indomethacin