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SKI306X, an oriental herbal mixture, suppresses gastric leukotriene B4 synthesis without causing mucosal injury and the diclofenac-induced gastric lesions.

Authors
Kim, JH; Rhee, HI; Jung, IH; Ryu, K; Jung, K; Han, CK; Kwak, WJ; Cho, YB; Joo, HJ
Citation
Life sciences, 77(11):1181-1193, 2005
Journal Title
Life sciences
ISSN
0024-32051879-0631
Abstract
SKI306X compound is a herbal mixture. This plant was in oriental medicine and was clinically approved for the treatment of osteoarthritis (OA) in Korea. SKI306X was previously found to have anti-inflammatory, analgesic and cartilage protective effects in several experimental models. In this study, SKI306X was investigated for its gastro-sparing effects on the gastric mucosa comparing with those of diclofenac, a conventional NSAID, and celecoxib, a cyclooxygenase-2 (COX-2) specific inhibitor. To investigate acute gastric damaging properties of SKI306X, the stomach of the animals was histologically and immuno-histochemically examined after single or repeated administration, and SKI306X demonstrated excellent gastric tolerability. SKI306X did not cause significant gastric irritation, erosion, or ulceration up to the orally administered dose of 2 g/kg and the intraperitoneal (i.p.) dose of 125 mg/kg. In contrast, diclofenac caused mucosal erosion, ulceration and bleeding at clinically effective doses. To determine the mode of gastro-sparing action, eicosanoid synthesis was examined in gastric mucosa and blood. SKI306X significantly decreased gastric and blood leukotriene B(4) (LTB(4)) production. However, SKI306X showed either no effect or a slight increase in levels of prostaglandin E(2) (PGE(2)). In addition, gastro-protective effects of SKI306X were exhibited by suppressing diclofenac-induced erosion and ulceration of gastric mucosa in a rat model and the possible mechanism of these effects were investigated. These studies demonstrated that SKI306X did not produce any significant damage up to dose of 2 g/kg and was effective in significantly protecting the damage associated to diclofenac-induced gastric ulcerations. SKI306X could spare the gastric mucosa through significantly suppressing gastric leukotriene (LT) synthesis.
MeSH terms
AnimalsAnti-Inflammatory Agents/adverse effectsAnti-Inflammatory Agents/pharmacology*Anti-Inflammatory Agents/therapeutic useAnti-Inflammatory Agents, Non-Steroidal*Cyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase Inhibitors/pharmacologyDepression, ChemicalDiclofenac*Dose-Response Relationship, DrugDrugs, Chinese Herbal/adverse effectsDrugs, Chinese Herbal/pharmacology*Drugs, Chinese Herbal/therapeutic useEicosanoids/biosynthesisGastric Mucosa/drug effectsGastric Mucosa/metabolismGastric Mucosa/pathology*Leukotriene B4/biosynthesis*MalePeroxidase/metabolismProstaglandin-Endoperoxide Synthases/metabolismPyrazoles/pharmacologyRatsRats, Sprague-DawleyStomach Ulcer/chemically induced*Stomach Ulcer/drug therapyStomach Ulcer/pathology*Sulfonamides/pharmacology
DOI
10.1016/j.lfs.2004.11.040
PMID
15935401
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
AJOU Authors
주, 희재
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