Preventive Effect of Mebicar and Ginsenoside Rg1 on Neurobehavioral and Immunological Disruptions Caused by Intermittent Unpredictable Stress in Mice

Objectives: Ginsenoside Rg1 and mebicar have been reported to have broad efficacy spectrum, including anti-anxiety and anti-stress. These drugs have been used not only for treatment but also for the purpose of increasing resistance from disease. A specific aim of this study was to investigate whether mebicar or ginsenoside Rg1 can prevent physiological changes resulting from intermittent unpredictable stress (IUS). Methods: Seven week-old Balb/cByJ mice were administered orally with mebicar (10 mg/kg) or ginsenoside Rg1 (10 mg/kg) starting from a week before they were exposed to IUS until the end of the experiment. IUS, which consists of psychological stress and physical fatigue, was set as 3 bouts (24 h/bout) exposure in a 2-week period. Results: IUS caused hyperactivity and anxiety-like behavior, which were not inhibited by mebicar or ginsenoside Rg1. IUS mice treated with mebicar or ginsenoside Rg1 recovered rapidly from anxiety-like behavior induced by the multiplexed stress compared to the mice not orally treated with mebicar or ginsenoside Rg1. Mebicar or ginsenoside Rg1 could not prevent the decrease of brain-derived neurotropic factor by IUS exposure. However, mebicar or ginsenoside Rg1 prevented elevation of serum corticosterone and secretion of proinflammatory cytokines from splenocytes due to IUS exposure. Conclusions: This study suggests that mebicar or ginsenoside Rg1 may have little preventive effect on neurobehavioral disruption by IUS exposure, but mebicar or ginsenoside Rg1 shortened the lasting duration of the anxiety caused by exposure to a novel environment. The anti-stress effect of mebicar and ginsenoside Rg1 may be restricted in peripheral stress responses.