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: Joo-Hyon Kim, Hae-In Rhee, In-Ho Jung, Keunho Ryu, Kiwon Jung, Chang-Kyun Han, Wie-Jong Kwak, Yong-Baik Cho, Hee-Jae Joo
• Journal: Life sciences (Life Sci) Vol. 77 Issue 11 Pg. 1181-93 (Jul 29 2005) ISSN: 0024-3205 [Print] Netherlands
• PMID: 15935401 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Drugs, Chinese Herbal
• Eicosanoids
• Pyrazoles
• SKI 306X
• Sulfonamides
• Diclofenac
• Leukotriene B4
• Peroxidase
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Celecoxib

Topics

• Animals
• Anti-Inflammatory Agents (adverse effects, pharmacology, therapeutic use)
• Anti-Inflammatory Agents, Non-Steroidal
• Celecoxib
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Depression, Chemical
• Diclofenac
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (adverse effects, pharmacology, therapeutic use)
• Eicosanoids (biosynthesis)
• Gastric Mucosa (drug effects, metabolism, pathology)
• Leukotriene B4 (biosynthesis)
• Male
• Peroxidase (metabolism)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pyrazoles (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Stomach Ulcer (chemically induced, drug therapy, pathology)
• Sulfonamides (pharmacology)