Effect of SKI 306X, a New Herbal Anti-Arthritic Agent, in Patients with Osteoarthritis of the Knee: A Double-Blind Placebo Controlled Study

Jung, Young Bok; Roh, Kwon-Jae; Jung, Jina; Jung, Kiwon; Yoo, Han‐Ill; Cho, Yong-Baik; Kwak, Wie-Jong; Kim, Dae‐Kee; Kim, Key H.; Han, Chang-Kyun

doi:10.1142/s0192415x01000502

Cited by 52 publications

(53 citation statements)

References 7 publications

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“…In previous studies, we reported the protective effects of SKI306X on rabbit articular cartilage and compared it with other OA drugs using in vivo models (9). A double blind and placebo-controlled study also confirmed the clinical efficacy and good tolerability of SKI306X in patients with OA in the knee (10). In another clinical study, this herbal extract was well tolerated by patients and demonstrated to have clinical efficacy comparable to that of diclofenac SR (slow released) (11).…”

Section: Introductionmentioning

confidence: 62%

SKI306X Suppresses Cartilage Destruction and Inhibits the Production of Matrix Metalloproteinase in Rabbit Joint Cartilage Explant Culture

et al. 2005

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Abstract. SKI306X was previously found to have cartilage protective effects in the experimental osteoarthritis (OA) model. To investigate the chondro-protective benefits of SKI306X for its capacity in altering changes in cartilage metabolism and molecular mechanisms of cartilage protective action, SKI306X is studied in rabbit cartilage explants culture. To investigate the protective effect of SKI306X on cartilage catabolism, we assessed collagen degradation in rabbit cartilage explants treated with interleukin-1α up to 3 weeks. To examine the reaction mechanism, matrix metalloproteinase (MMPs) were investigated by fluorimetric and Western blotting analysis. In addition, its effects on the activation process of proenzyme MMP-3 were determined by gelatin zymography. SKI306X significantly inhibited collagen degradation and inhibited the activities of several MMPs. Total MMPs activities in cultured medium were substantially increased in the third week at the time of collagen degradation with the absence of SKI306. However, the introduction of SKI306X decreased MMPs activities in cultured medium. Furthermore, Western blotting analysis proved that these inhibitory effects of this drug were the result of inhibiting MMPs expression. SKI306X also inhibited the activation of proenzyme MMP-3 to the active form of MMP-3. These results indicate that SKI306X inhibits matrix degradation by down regulating MMPs expression and secretion, inhibition of MMPs activity, and inhibiting activation of MMP-3 during the collagen breakdown process.

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Section: Introductionmentioning

confidence: 62%

SKI306X Suppresses Cartilage Destruction and Inhibits the Production of Matrix Metalloproteinase in Rabbit Joint Cartilage Explant Culture

et al. 2005

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“…Recent clinical trial suggested that extracted mixture of Clematis exerted protective effects on OA 13. However, the precise mechanism and responsible molecules for this effect are not obvious presently.…”

Section: Introductionmentioning

confidence: 99%

Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL‐1β/NF‐κB pathway

Wang¹,

Huang²,

Zhou³

et al. 2017

J Cellular Molecular Medi

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The osteoarthritis (OA) progression is now considered to be related to inflammation. Anemonin (ANE) is a small natural molecule extracted from various kinds of Chinese traditional herbs and has been shown to inhibiting inflammation response. In this study, we examined whether ANE could attenuate the progression of OA via suppression of IL‐1β/NF‐κB pathway activation. Destabilization of the medial meniscus (DMM) was performed in 10‐week‐old male C57BL/6J mice. ANE was then intra‐articularly injected into joint capsule for 8 and 12 weeks. Human articular chondrocytes and cartilage explants challenged with interleukin‐1β (IL‐1β) were treated with ANE. We found that ANE delayed articular cartilage degeneration in vitro and in vivo. In particular, proteoglycan loss and chondrocyte hypertrophy were significantly decreased in ANE ‐treated mice compared with vehicle‐treated mice. ANE decreased the expressions of matrix metalloproteinase‐13 (MMP13), A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), collagen X (Col X) while increasing Aggrecan level in murine with DMM surgery. ANE treatment also attenuated proteoglycan loss in human cartilage explants treated with IL‐1β ex vivo. ANE is a potent protective molecule for OA; it delays OA progression by suppressing ECM loss and chondrocyte hypertrophy partially by suppressing IL‐1β/NF‐κB pathway activation.

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“…SKI306X had been reported to have protective effects in articular cartilage. 5) The double blind, placebo-controlled study also confirmed the clinical efficacy and good tolerability of SKI306X in patients with OA in the knee 6) and in another clinical study, this herbal extract was well tolerated and demonstrated clinical efficacy comparable to that of diclofenac SR (slow released). Another clinical study is underway to determine the efficacy of SKI306X in RA patients.…”

mentioning

confidence: 66%

Effects of SKI306X on Arachidonate Metabolism and Other Inflammatory Mediators

Kim

Ryu

Jung

et al. 2005

Biological & Pharmaceutical Bulletin

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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.

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Effect of SKI 306X, a New Herbal Anti-Arthritic Agent, in Patients with Osteoarthritis of the Knee: A Double-Blind Placebo Controlled Study

Cited by 52 publications

References 7 publications

SKI306X Suppresses Cartilage Destruction and Inhibits the Production of Matrix Metalloproteinase in Rabbit Joint Cartilage Explant Culture

SKI306X Suppresses Cartilage Destruction and Inhibits the Production of Matrix Metalloproteinase in Rabbit Joint Cartilage Explant Culture

Anemonin attenuates osteoarthritis progression through inhibiting the activation of IL‐1β/NF‐κB pathway

Effects of SKI306X on Arachidonate Metabolism and Other Inflammatory Mediators

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