Biol. Pharm. Bull. 28(8) 1389—1393 (2005)

quence of the production of excess free radicals, such as reactive oxygen species, and provides marked damage to the structure and function of cell membranes in various tissues. Particularly, the brain is susceptible to free radical insults because it contains a high concentration of easily peroxidizable polyunsaturated fatty acids, and is not particularly enriched in protective antioxidant enzymes or other antioxidant compounds. Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been demonstrated to produce oxidative damage to membrane lipid in the brain. In a previous study, mice exposed to psychological stress by a communication box paradigm also showed oxidative membrane damage due to enhanced lipid peroxidation in the brain. On the other hand, protracted social isolation of laboratory animals after weaning has been believed to be stressful because it produces a variety of physiological disturbances such as increases of corticosterone, ACTH and catecholamine levels in the serum and abnormal behaviors such as aggressiveness, hyperlocomotion, and anxietylike behavior as the products of prolonged stress. Moreover, previous studies have demonstrated that protracted social isolation of male mice induces hyperactivity of central noradrenergic and corticotropin releasing factor systems and reduced function of g-aminobutyric acid (GABA)-ergic system in the brain. However, no information is, so far, available if exposure of laboratory animals to protract socially isolation stress, another kind of psychological stress produces oxidative damage in the brain. Vietnamese ginseng (Panax vietnamensis HA et GRUSHV., Araliaceae) extract and total saponin have been shown to exert an inhibitory effect on lipid peroxidation reaction caused by the free radical generating system in the mouse brain and liver homogenates, while its major saponin constituent, majonoside-R2, failed to affect the reaction. However, it was found that when administered systemically, majonoside-R2 produced a protective effect on psychological stress-induced brain cell membrane damage by reducing an increase in thiobarbituric reactive substances (TBARS) in the brain, an index of lipid peroxidation, and that this in vivo antioxidant effect of majonoside-R2 was partly due to facilitation of GABAergic systems in the brain. Thus, in this study, we attempted to investigate: (1) whether social isolation stress induces oxidative damage to the mouse brain, (2) if it does, whether majonoside-R2 produces a protective effect on social isolation stress-induced oxidative stress, and (3) possible mechanisms involved in the antioxidant effect of majonoside-R2.