title: SKI306X, an oriental herbal mixture, suppresses gastric leukotriene B4 synthesis without causing mucosal injury and the diclofenac-induced gastric lesions.
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.
authors.affiliation: Life Science Research Center, SK Chemicals, 600 Jungja-1-Dong, Changan-Ku, Suwon-Si, Kyungki-Do 440-745, Korea.
authors.forename: Joo-Hyon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hae-In
authors.initials: HI
authors.lastname: Rhee
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Jung
authors.forename: Keunho
authors.initials: K
authors.lastname: Ryu
authors.forename: Kiwon
authors.initials: K
authors.lastname: Jung
authors.forename: Chang-Kyun
authors.initials: CK
authors.lastname: Han
authors.forename: Wie-Jong
authors.initials: WJ
authors.lastname: Kwak
authors.forename: Yong-Baik
authors.initials: YB
authors.lastname: Cho
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Joo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003864:Depression, Chemical; D004008:Diclofenac; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D015777:Eicosanoids / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004365:Drugs, Chinese Herbal; D015777:Eicosanoids; D011720:Pyrazoles; C460104:SKI 306X; D013449:Sulfonamides; D004008:Diclofenac; D007975:Leukotriene B4; D009195:Peroxidase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib