The abnormal maturation and ossification of articular chondrocytes play a central role in the pathogenesis of osteoarthritis (OA). Inhibiting the enzymatic degradation of the extracellular matrix and maintaining the cellular phenotype are two of the major goals of interest in managing OA. Ginseng is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. Ginsenoside Rb1, a major component of ginseng that contains an aglycone with a dammarane skeleton, has been reported to exhibit various biological activities, including anti-inflammatory and anti-tumor effects. However, a chondroprotective effect of ginsenoside Rb1 related to OA has not yet been reported. The purpose of this study was to demonstrate the chondroprotective effect of ginsenoside Rb1 on the regulation of pro-inflammatory factors and chondrogenic genes. Cultured rat articular chondrocytes were treated with 100 μM ginsenoside Rb1 and/or 500 μM hydrogen peroxide (H2O2) and assessed for viability, reactive oxygen species production, nitric oxide (NO) release, and chondrogenic gene expression. Ginsenoside Rb1 treatment resulted in reductions in the levels of pro-inflammatory cytokine and NO in H2O2-treated chondrocytes. The expression levels of chondrogenic genes, such as type II collagen and SOX9, were increased in the presence of ginsenoside Rb1, whereas the expression levels of inflammatory genes related to chondrocytes, such as MMP1 and MMP13, were reduced by approximately 50%. These results suggest that ginsenoside Rb1 has potential for use as a therapeutic agent in OA patients.
BackgroundThe beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress.MethodsRaw 264.7 cells were pretreated with GRo (up to 200μM) for 1 h before treatment with 1 μg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated.ResultsGRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells.ConclusionGRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.
Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide (H2O2), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside Rb1 (GRb1) is the principal component in ginseng and has been shown to have a variety of biological activities, such as anti-arthritis, anti-inflammation, and anti-tumor activities. In this study, we evaluated the effects of G-Rb1 on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by H2O2. Cultured rat articular chondrocytes were exposed to H2O2 with or without G-Rb1 and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-Rb1 showed an inhibition of MPT, caspase-3 activity, and cell death. Additionally, the levels of the apoptotic protein Bax were significantly lower and the levels of the anti-apoptotic protein Bcl-xL were higher compared with H2O2 treatment alone. The results of this study demonstrate that G-Rb1 protects chondrocytes against H2O2-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-Rb1 is a potentially useful drug for the treatment of OA patients.
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