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.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Duodenal Ulcer/prevention & control , Herbal Medicine , Indomethacin/toxicity , 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 , Duodenal Ulcer/chemically induced , Duodenal Ulcer/mortality , Female , Gastrointestinal Hemorrhage/prevention & control , Indomethacin/administration & dosage , 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 OutcomeABSTRACT
The aqueous extract of the Chinese crude drug Alismatis rhizoma, a dried rhizome of Alisma orientale Juzepczuk, exhibited in vitro inhibitory activities on angiotensin II and arginine vasopressin binding to their receptors. A fractionation study on the extract clarified that the known terpenoidal constituents; i.e., alisols A and B, 23-O-acetylalisol B, and alismol, were responsible for the activities. Furthermore, investigation of commercial samples of the crude drug demonstrated striking differences in their activities dependent on their locality of origin due to a difference in the amounts of these active principles. Therefore, the content of these principles could be utilized as a criteria of quality of the crude drug Alismatis rhizoma.