An herbal medicine orengedokuto prevents indomethacin-induced enteropathy

Naoko Miura; Masato Fukutake; Masahiro Yamamoto; Nobuhiro Ohtake; Seiichi Iizuka; Sachiko Imamura; Naoko Tsuchiya; Makoto Ishimatsu; Yuichi Nakamura; Atsushi Ishige; Kenji Watanabe; Yoshio Kase; Shuichi Takeda

doi:10.1248/bpb.30.495

An herbal medicine orengedokuto prevents indomethacin-induced enteropathy

Biol Pharm Bull. 2007 Mar;30(3):495-501. doi: 10.1248/bpb.30.495.

Authors

Naoko Miura¹, Masato Fukutake, Masahiro Yamamoto, Nobuhiro Ohtake, Seiichi Iizuka, Sachiko Imamura, Naoko Tsuchiya, Makoto Ishimatsu, Yuichi Nakamura, Atsushi Ishige, Kenji Watanabe, Yoshio Kase, Shuichi Takeda

Affiliation

¹ Central Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. miura_naoko@mail.tsumura.co.jp

PMID: 17329845
DOI: 10.1248/bpb.30.495

Abstract

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.

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Anti-Inflammatory Agents, Non-Steroidal / toxicity
Cyclooxygenase 2 Inhibitors / pharmacology
Dinoprostone / metabolism
Dose-Response Relationship, Drug
Drugs, Chinese Herbal / pharmacology
Drugs, Chinese Herbal / therapeutic use*
Duodenal Ulcer / chemically induced
Duodenal Ulcer / mortality
Duodenal Ulcer / prevention & control*
Female
Gastrointestinal Hemorrhage / prevention & control
Herbal Medicine*
Indomethacin / administration & dosage
Indomethacin / toxicity*
Injections, Subcutaneous
Interleukin-10 / metabolism
Intestinal Mucosa / drug effects
Intestinal Mucosa / metabolism
Intestinal Mucosa / pathology
Intestine, Small / drug effects
Intestine, Small / metabolism
Intestine, Small / pathology
Leukocytes, Mononuclear / drug effects
Leukocytes, Mononuclear / metabolism
Mice
Mice, Inbred BALB C
Nitrobenzenes / pharmacology
Sulfonamides / pharmacology
Survival Analysis
Survival Rate
Treatment Outcome

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Drugs, Chinese Herbal
Nitrobenzenes
Sulfonamides
oren gedoku to
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Interleukin-10
Dinoprostone
Indomethacin