ECM consists of mainly collageneous materials and aggrecans [1], which are AT13387 mw maintained under the control of a normal turnover process between new ECM synthesis by residing chondrocytes and breakdown by matrix metalloproteinases (MMPs) and aggrecanases. In certain pathological conditions, such as osteoarthritis, however, some MMPs are highly induced and degrade ECM. Among the MMPs, MMP-13 is the most important collagenase to degrade and destabilize ECM in human articular cartilages [2], [3] and [4]. In this regard, it is thought that MMP-13 inhibitor(s) and/or downregulator(s) may play a beneficial therapeutic role of chondroprotection. Korean

Red Ginseng (steamed white ginseng, Panax ginseng Meyer) is famous for possessing various biological effects, including enhancing vital energy, enhancing immune capacity, and inhibition of cancer cell growth. Its major Anti-cancer Compound Library constituents are various ginsenosides that have been reported to exhibit numerous pharmacological activities, including vitality

enhancement, immune modulation, and anticancer activity [5], [6] and [7]. However, few investigations or few clinical studies of ginsenosides on cartilage degradation disorders have been reported. Among the ginsenosides from Korean Red Ginseng, some are not present in white ginseng products [8] and [9]. Examples are ginsenoside Rg3, Rg5, Rk1, and F4 that are only detected in red ginseng extract. Previously, one ginsenoside, Rg3, was found to inhibit MMP-13 expression in human osteoarthritic chondrocytes [10]. We have recently found that certain ginsenosides including Rc, Rd, Rf, F4, Rg1, and Rg3 inhibit MMP-13 induction from human chondrocytes, and some also block glycosaminoglycan (GAG) release from interleukin (IL)-1α-treated cartilage culture to some degree [11]. These previous findings strongly suggest that the Korean Red Ginseng products and/or some ginsenoside-enriched preparations

may possess a significant inhibitory activity of MMP-13 expression and thereby block cartilage degradation. Thus, several ginseng preparations have cAMP been designed and prepared in the present study. They were examined for MMP-13 downregulatory effect and cartilage protection to find a potential for a new chondroprotective agent. This is the first report of the preparations from Korean Red Ginseng and ginseng leaves to show MMP-13 downregulating properties. Human IL-1α, IL-1β, dexamethasone, diclofenac, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and anti-MMP-13 antibody were purchased from Sigma–Aldrich (St Louis, MO, USA). Dulbeccos’s modified Eagle’s medium (DMEM) and other cell culture reagents including fetal bovine serum (FBS) were products of Gibco BRL (Grand Island, NY, USA). The protein assay kit was purchased from Bio-Rad (Hercules, CA, USA).