Protective Effect of DA-9601, an Extract of Artemisiae Herba, against Naproxen-induced Gastric Damage in Arthritic Rats

  • Oh, Tae-Young (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Ryu, Byong-Kweon (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Ko, Jun-Il (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Ahn, Byoung-Ok (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Kim, Soon-Hoe (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Kim, Won-Bae (Research Laboratories, Dong-A Pharm. Co. Ltd) ;
  • Lee, Eun-Bang (Natural Products Institute, Seoul National University) ;
  • Jin, Joo-Hyun (Department of Gastroenterology, College of Medicine, Ajou University) ;
  • Hahm, Ki-Baik (Department of Gastroenterology, College of Medicine, Ajou University)
  • Published : 1997.10.01

Abstract

Gastrointestinal irritation is the most frequent adverse effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAIDs) for the treatment of arthritic conditions. Gastroprotective effect of DA-9601, a new antiulcer agent from Artemisiae Herba extract, against NSAID was evaluated in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of naproxen (30 mg/kg), one of the most commonly used NSAID, induced apparent gastric lesions as well as a significant decrease in mucosal prostagiandin $E_2;(PGE_2)$ and prostagiandin F_${1{\alpha}}$$(PGF_{1{\alpha}})$ levels. Coadministration of DA-9601 prevents naproxen-induced mucosal injury and depletion of prostaglandins, in a dose-related manner. DA-9601 did not alter the antiinflammatory or analgesic effect of naproxen. The present results suggest that DA-9601 may be useful as a mucoprotectant against NSAIDs in clinical practice.

Keywords

References

  1. Ann. Intern. Med. v.115 Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. Agrawal,N.M.;Roth,S.;Graham,D.Y.;White,R.H.;Germain,B.;Brown,J.A.;Stromatt,S.C.
  2. Dig. Dis. v.12 Cytoprotection with misoprostol: use in the treatment and preventions of ulcers Ballinger,A.
  3. Ann. Intern. Med. v.85 Aspirin induced ultrastructural changes in human gastric mucosa Baskin,W.N.;Ivey,K.J.;Krause,W.J.;Jeffrey,G.E.;Gemmell,R.T.
  4. New Engl. J. Med. v.325 Comparison of an anti-inflammatoty dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee Bradley,J.D.;Brandt,K.D.;Katz,B.P.;Kalasinski,L.A.;Ryan,S.I.
  5. J. Pharm. Exp. Ther. v.214 Suprofen, a new peripheral analgesic Capetola,R.J.;Shriver,D.A.;Rosenthale,M.E.
  6. Br. Med. J. v.280 Gastroscopic evaluation of antiinflammatory agents Caruso,J.;Porro,G.B.
  7. Asia Pacific J. Pharmacol v.2 Potentiation of indomethacin-induced gastric ulcers in rats by nordihydroguaiaretic acid (VDGA), an inhibitor of lipoxygenase Cho,C.H.;Ogle,C.W.
  8. J.Clin. Pharm. Ther. v.16 Misoprostol: a logical therapeutic approach to gastroduodenal mucosal injury induced by non-steroidal anti-inflammatory drugs? Fenn,G.C.;Robinson,G.C.
  9. Gastroenterology v.96 Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Fries,J.F.;Miller,S.R.;Spitz,B.W.;Williams,C.A.;Hubert,H.B.;Bloch,D.A.
  10. Ann. Intern. Med. v.115 Risk for serious gastrointestinal complications related use of nonsteroidal anti-inflammatory drugs: a meta-analysis Gabriel,S.E.;Jaakkimainen,L.;Bombardier,C.
  11. Gastroenterology v.96 Prevention of gastroduodenal injury induced by chronic nonsteroidal antiinflammatory drug therapy Graham,D.Y.
  12. Lancet v.ⅱ Prevention of NSAID-induced gastric ulcer with misoprostol: Multicentre, double blind, placebo-controlled trial Graham,D.Y.;Agrawal,N.M.;Roth,S.H.
  13. Ann. Intern. Med. v.119 Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Graham,D.Y.;White,R.H.;Moreland,L.W.;Schubert,T.T.;Katz,R.;Jaszewski,R.;Tindall,E.;Triadafilopoulos.G.;Stromatt,S.C.;Teoh,L.S.
  14. Gastroenterology v.89 Prostaglandins and the gastrointestinal mucosa: are they important in in its function, disease or treatment? Hawkey,C.J.;Rampton,D.S.
  15. Drug Safety v.12 Misoprostol/NSAID fixed combination: Help or hindrance in clinical practice? Isdale,A.;Wright,V.
  16. Facts and Comparison Kastrup,E.K.
  17. J. Rheumatol. v.13 Rioprostill prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dogs and atrhritic rats Katz,L.B.;Capetola,R.J.;Argentieri,D.C.;Moore,L.E.;Genna,T.;Porter,M.C.;Jasty,V.;Hartnagel,R.E.;Abrutyn,D.;Shriver,D.A.
  18. J. Appl. Pharmacol. v.4 Four-week oral toxicity study of DA-9601, an antiulcer agent of Artemisia spp. extract, in rats Kim,O.J.;Kang,K.K.;Kim,D.H.;Baik,N.G.;Ahn,B.O.;Kim,W.B.;Yang,J.
  19. Gastroenterology v.93 Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation Kitahora,T.;Guth,P.H.
  20. J. Appl. Pharmacol. v.4 General pharmacology of Artemisia extract powder, DA-9601 Lee,E.B.;Cheon,S.A.;Lee,E.S.;Kim,O.K.;Ko,S.T.;Yu,K.J.;Shin,D.S.;Kang,S.Y.;Kim,S.H.;Sohn,M.H.
  21. Aliment. Pharmacol. Ther. v.10 Gastric mucosal injury and adaptation to oral and rectal administration of naproxen Lipscomb,G.R.;Rees,W.D.W.
  22. Gastroenterology v.109 Indomethacin-induced gastric injury and leukocyte adherence in arthritic versus healthy rats McCafferty,D.M.;Granger,D.N.;Wallace,J.L
  23. J. Appl. Pharmacol. v.4 Studies on antiulcer effects of DA-9601, an Artemisiae Herba extract against experimental gastric ulcers and its mechanism Oh,T.Y.;Ryu,B.K.;Park,J.B.;Lee,S.D.;Kim,W.B.;Y,J.;Lee,E.B.
  24. J. Appl. Pharmacol. v.5 Studies on protective effect of DA-9601, an Artemisiae Herba extract, against ethanol-induced gastric mucosal damage and its mechanism Oh,T.Y;Ahn,B.O.;Ko,J.I.;Ryu,B.K.;Son,M.W.;Kim,S.H.;Kim,W.B.;Lee,E.B.
  25. Agents Actions v.44 Mechanisms of gastrointestinal damage by NSAIDs Rainsford,K.D.
  26. Arch. Intern. Med. v.147 Nonsteroidal anti-inflammatory drugs gastropathy. Recognition and response Roth,S.H.;Bennett,R.E.
  27. Am. J. Med. v.86 Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage Schoen,R.T.;Vender,R.J.
  28. New Engl. J. Med. v.302 Drug therapy: nonsteroidal antiinflammatory drugs Simon,L.S.;Mills,J.A.
  29. Ann. Intern. Med. v.114 Nonsteroidal anti-inflammatory drugs and peptic ulcer disease Soll,A.H.;Weinstein,W.M.;Kurata,J.;Mc Carthy,D.
  30. Can. J. Physiol. Pharmacol. v.71 Gastric ulceration: critical events at the neutrophil-endothelium interface Wallace.J.L.
  31. DA-9601, antiulcer agent, Final report of Good Health R&D Program Yang,J.