Anti-apoptotic Activity of Ginsenoside Rb1 in Hydrogen Peroxide-treated Chondrocytes: Stabilization of Mitochondria and the Inhibition of Caspase-3원문보기
Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide ($H_2O_2$), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside $Rb_1$ (G-$Rb_1$) is the p...
Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide ($H_2O_2$), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside $Rb_1$ (G-$Rb_1$) 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-$Rb_1$ on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by $H_2O_2$. Cultured rat articular chondrocytes were exposed to $H_2O_2$ with or without G-$Rb_1$ and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-$Rb_1$ 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 $H_2O_2$ treatment alone. The results of this study demonstrate that G-$Rb_1$ protects chondrocytes against $H_2O_2$-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-$Rb_1$ is a potentially useful drug for the treatment of OA patients.
Chondrocyte apoptosis has been recognized as an important factor in the pathogenesis of osteoarthritis (OA). Hydrogen peroxide ($H_2O_2$), which produces reactive oxygen species, reportedly induces apoptosis in chondrocytes. The ginsenoside $Rb_1$ (G-$Rb_1$) 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-$Rb_1$ on the mitochondrial permeability transition (MPT) and caspase-3 activity of chondrocyte apoptosis induced by $H_2O_2$. Cultured rat articular chondrocytes were exposed to $H_2O_2$ with or without G-$Rb_1$ and assessed for viability, MPT, Bcl-xL/Bax expression, caspase-3 activity, and apoptosis. The co-treatment with G-$Rb_1$ 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 $H_2O_2$ treatment alone. The results of this study demonstrate that G-$Rb_1$ protects chondrocytes against $H_2O_2$-induced apoptosis, at least in part via the inhibition of MPT and caspase-3 activity. These results demonstrate that G-$Rb_1$ is a potentially useful drug for the treatment of OA patients.
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문제 정의
The results of previous studies have also demonstrated that G-Rb1 may function as a scavenger of toxic species, such as H2O2 [6,11]. The principal objective of the present study, therefore, was to determine whether G-Rb1 treatment results in the inhibition of both the mitochondrial permeability transition (MPT) and caspase-3 in H2O2-treated chondrocytes.
제안 방법
The blots were then incubated with peroxidase-conjugated goat anti-rabbit IgG (1:5,000; Millipore, Bedford, MA, USA) for 1 h. The immunoreactions were visualized with SuperSignal West Dura Extended Duration Substrate (Thermo Scientifi c, San Jose, CA, USA) and analyzed using a chemiImager analyzer system (Alpha Innotech, San Leandro, CA, USA).
데이터처리
The data were analyzed via Student’s t-test and a repeated measures ANOVA followed by a Bonferroni test.
성능/효과
Bcl-xL has been reported to maintain cell viability after the activation of caspases [20]. In conclusion, the results of this study demonstrated the protective effect of G-Rb1 with anti-apoptotic effects in chondrocytes and suggested that G-Rb1 might prove useful as a novel preventive agent against H2O2-induced cytotoxicity.
MPT caused by ROS is dependent on non-selective inner membrane permeabilization that may precede actual apoptotic cell death [14,15]. Our results demonstrated that G-Rb1 had strong MPT inhibition effects similar to C3, the caspase-3 inhibitor, in H2O2-treated chondrocytes (Fig. 2). Additionally, the expression of the antiapoptotic protein Bcl-xL was increased in H2O2-treated chondrocytes after G-Rb1 treatment (Fig.
Ginsenosides are unique saponins that exist only in ginseng, and they have a variety of pharmacological effects, such as anticancer activities [10]. The results of the present study demonstrated that Rb1, one of the principal active ingredients in ginseng, can protect chondrocytes against H2O2-induced apoptotic insults. Thus, we demonstrated that in vitro treatment with G-Rb1 exerted protective effects against H2O2-induced cytotoxicity in rat articular chondrocytes (Fig.
참고문헌 (20)
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