Ginsenoside-Rd attenuates oxidative damage related to aging in senescence-accelerated mice

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Abstract
Among the various theories of the aging process, the free radical theory, which proposes that deleterious actions of free radicals are responsible for the functional deterioration associated with aging, has received widespread attention. The theory suggests that enhancement of the antioxidative defence system to attenuate free‐radical‐induced damage will counteract the aging process. We used senescence‐accelerated mice (SAM) to investigate the relationship between aging and the antioxidative defence system and evaluated the effects of ginsenoside‐Rd, the saponin from ginseng, by measuring antioxidative defence system parameters, including the glutathione (GSH)/glutathione disulfide (GSSG) redox status, antioxidative enzyme activity and level of lipid peroxidation. SAM at 11 months of age (old SAM) showed a significantly lower hepatic GSH/GSSG ratio, due to decreased GSH and increased GSSG levels, than SAM at 5 weeks of age (young SAM). However, the administration of ginsenoside‐Rd at a dose of 1 or 5 mg kg−1 daily for 30 days to 10‐month‐old SAM significantly increased GSH, but decreased GSSG, resulting in elevation of the GSH/GSSG ratio. In addition, ginsenoside‐Rd increased the activity of glutathione peroxidase (GSH‐Px) and glutathione reductase that were both significantly lower in old SAM than in young SAM. This suggests that ginsenoside‐Rd could play a crucial role in enhancing the defence system through regulation of the GSH/GSSG redox status. Moreover, decreases in the superoxide dismutase (SOD) and catalase activity in old SAM compared with young SAM were also revealed, indicating that the aging process resulted in suppression of the antioxidative defence system. However, ginsenoside‐Rd did not affect SOD and catalase activity. As catalase is localized in peroxisome granules and GSH‐Px is present in the cytoplasm and mitochondrial matrix, the site of ginsenoside‐Rd action may be the cytoplasm and mitochondrial matrix. Furthermore, the serum and liver malondialdehyde levels, indicators of lipid peroxidation, were elevated with aging, while ginsenoside‐Rd inhibited lipid peroxidation. This study indicates that the aging process leads to suppression of the antioxidative defence system and accumulation of lipid peroxidation products, while ginsenoside‐Rd attenuates the oxidative damage, which may be responsible for the intervention of GSH/GSSG redox status.