Effects of SKI306X on Arachidonate Metabolism and Other Inflammatory Mediators

Abstract

SKI306X was previously reported to have good anti-inflammatory and analgesic efficacy in various studies. To determine its mode of action, an investigation was carried out for some representative mediators. Arachidonic acid metabolism and its products are particularly important in inflammation and pain. The pro-inflammatory cytokines, especially interleukin-1 (IL-1) and tumor necrosis factor (TNF-a a), and induced nitric oxide (NO) appear to be most involved in the inflammatory process such as osteoarthritis (OA). Thus SKI306X was tested to determine the effects on enzymes related to arachidonic acid metabolism and the release or synthesis of inflammatory mediators. SKI306X did inhibit the expression of cyclooxygenase-2 (COX-2) enzyme without affecting COX-1 and COX-2 activity. Leukotriene B 4 (LTB 4 ) production also was inhibited by SKI306X (IC 50 ‫62.4؎7.89؍‬ m mg/ml). SKI306X inhibited significantly TNF-a a release (IC 50 ‫8.71؎6.79؍‬ m mg/ml) and NO production (IC 50 ‫؍‬ 280؎17.8 m mg/ml). But IL-1a a release was not attenuated by SKI306X. This study suggests that inhibition of these mediators by SKI306X may be one of the mechanisms responsible for its anti-inflammatory effects.

Saponin-rich fraction from Clematis chinensis Osbeck roots protects rabbit chondrocytes against nitric oxide-induced apoptosis via preventing mitochondria impairment and caspase-3 activation

“…Recently, a great variety of herbal remedies have been proposed for OA therapy, such as Capparis spinosa extracts (Panico et al 2005), green tea polyphenols (Ahmed et al 2004), genistein (Hooshmand et al 2007), resveratrol (Csaki et al 2008), curcumin (Shakibaei et al 2007), etc. Many plants from Clematis species have been demonstrated to possess anti-inflammatory and chondro-protective effects (Choi et al 2002;Kim et al 2005a;Kim et al 2005b; Lee et al 2005;Li et al 2006;Park et al 2006). Among them, Clematis chinensis Osbeck (Ranunculaceae), which is mainly distributed in southern China and contains several triterpenoid saponins (Mimaki et al 2004), has long been used in traditional Chinese medicine to treat joint diseases including OA.…”

Comparison of pharmacokinetics and safety of fixed-dose combination of SKI306X and aceclofenac versus separate tablets in healthy subjects

“…[1] SKI306X has been widely used in combination with aceclofenac in Korea for pain control in OA. [6] Even though the active moiety of SKI306X and its metabolites has not been established and its pharmacokinetic (PK) characteristics are unknown, [7] SKI306X has demonstrated efficacy in pain control and protective effects in articular cartilage through its anti-inflammatory and immunomodulatory actions without notable side effects. [1,[7][8][9] In addition, SKI306X did not influence the PK and safety of aceclofenac when it was concomitantly administered.…”

“…[10,16] SKI306X is used commonly in Korea for pain control in OA. [17] It has demonstrated efficacy in pain control and protective effects in articular cartilage [1,8,9] In a randomized, double-blinded study in which the efficacy and safety of SKI306X were compared with those of diclofenac in patients with OA, SKI306X demonstrated efficacy statistically comparable to that of diclofenac and was well tolerated. [18] In addition, SKI306X did not influence the PK and safety of aceclofenac in co-administration.…”

The Role of Chondroprotectants, Nutraceuticals, and Nutrition in Rehabilitation

“…[298][299][300][301][302][303] Extracts from Clematis vitalba exhibit antiinflammatory, antinociceptive, and antipyretic effects in induced osteoarthritis in mice. In vitro studies show SKI 306X or Clematis inhibits cartilage degradation, chondrocyte apoptosis, and production of tumor necrosis factor α and interleukin-1 β.…”