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

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• 作者：Kim ; Joo-Hyon ; Rhee ; Hae-In ; Jung ; In-Ho ; Ryu ; KeunHo ; Jung ; Kiwon ; Han ; Chang-Kyun ; Kwak ; Wie-Jong ; et. al.
• 关键词：SKI 306X ; Gastric mucosa ; Prostaglandin ; Leukotriene
• 刊名：Life Sciences
• 出版年：2005
• 出版时间：July 29, 2005
• 年：2005
• 卷：77
• 期：11
• 页码：1181-1193
• 全文大小：2.16 M

文摘

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 B₄ (LTB₄) production. However, SKI306X showed either no effect or a slight increase in levels of prostaglandin E₂ (PGE₂). 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.