| Stress is a nonspecific response of the body to the external stimulation, including pressures from society and environment, leading to physiological stress and psychological stress. Strong stress is often the most important reason to induce mental disorders, and the different intensity and lasting time of stress can make a difference result in behavior. Suffered from acute stress, individuals showed high arousal and the memory enhancement in fear events related to environment cues, and always resulting in the occurrence of post-traumatic stress disorder, with core symptoms of irritability, anger, sleep disorders, high alert status, and the increase of the startle reflex. While Chronic stress can lead to the results of anhedonia, anxiety, and other depression behavior characteristics. The balance between excitatory amino acids and inhibitory amino acid is broken in the brain when the body was subjected to stress, and it is one of the important neural molecular mechanisms of the mental disorders. By adjusting the excitatory and inhibitory amino acid to restore its balance. Therefore, it is an important way to develop anti-stress drugs by screening the modulators of amino acids content in brain.Cynanchum otophyllum, belonging to genus Cynanchum(Asclepiadaceae), is a folk medicine used in the southwest of China. The active components are total glycosides(QYS) isolated from the roots of the plant. It was reported that QYS can increase GABA content and reduce excitatory amino acids content, including glutamic acid and asparagi glycine in epilepsy patient’s brain, suggesting that C. otophyllum can be used to modulate the balance of amino acids and treat the mental disorders caused by stress.In this research, we use acute stress and chronic stress animal model to evaluate Cynanchum otophyllum’s anti-stress effect.1. The effect of anti-acute stressi) QYS has no significant difference to animals’ startle reflex. Both mid dose(10mg/kg) and high dose(30mg/kg) of QYS could inhibit fear situation startle under 105 d B startle reflex(p=0.045,p=0.045).High dose of QYS could inhibit fear situation startle under 115 d B startle reflex(p=0.05).ii)QYS could inhibit the startle under105 d B,which induced by fear clues[F(3,45)=3.083,p<0.05],with high dose of QYS has significant inhibition effect(p=0.018),but mid dose of QYS only has inhibition trend(p=0.08).The low dose of QYS has no significant inhibition effect(p=0.49). Under the condition of 115 d B noise, QYS has certain inhibition to startle enhancement induced by fear cues(p=0.08).iii)In various dose of QYS cannot enhance startle under fear cues induced by 95 d B.iv) In the open field test,QYS cannot change the percentage of immobility time(p>0.05),but different doses have different effects on it. At 0-2.5min and 5-7.5min period,the mid dose of QYS can enhance the immobility time significantly(p=0.048;p=0.025).In the final 2.5min of 10min(7.5-10min),with the higher dose, the immobility has a downward trend[F(2,33)=3.006,p=0.063].In 7.5 minutes, the dose 10mg/kg of QYS can significantly inhibit the activity of the animal(p=0.016;p=0.041;p=0.01).At 7.5-10 min period, the activity of animal become enhancement by the increase concentration of QYS.Acute stress effect of the experimental results show that QYS could significantly inhibit startle enhanced induced by fear context and fear cue. It reveal that QYS has inhibitory effect on mental disorder induced by acute stress.2. The effect of anti-chronic stress: social defeat strong chronic stress and chronic unpredictable mild stress animal modeli) After social defeat chronic stress 8 days, the high dose(45mg/kg) of QYS could be able to reverse the sugar preference(p=0.024),which shows QYS can restore the symptoms of lack of pleasure induced by social defeat stress. In the social interaction experiment,QYS has no significant effect on both social female preference [F(3,37)=0.48,P=0.698>0.05]and social avoid LE[F(3,32)=0.94,p=0.434>0.05],but low dose and high dose QYS has downward trend to reduce social time.The mid dose of QYShas a tendency to inhibit startle induced by 95 d B,the same tendency to high dose of QYS induced by 105 d B.ii) In the CUMS experiment,the high dose of QYS has a tendency to restore the sugar water preference(p=0.066) at the 3rd week.At the forth week,45mg/kg QYS can significantly restored the sugar water preference after CUMS(p=0.016<0.05).At the 5th week,both mid and high dose QYS can significantly restore sugar water preference(p=0.003<0.01;p=0.005<0.01).In the open field test,45mg/kg QYS can significantly enhance the immobility time(p=0.005<0.01),which increase with the rising concentration of QYS,the same situation to animal activity(p=0.006<0.01;p=0.002<0.01).But QYS has no effect on crossing the central area of open field[F(3,41)=0.496,P=0.687>0.05].The social behavior of animal in CUMS,QYS has no significant effect.The above results show that QYS has good effect on both acute stress and chronic stress. |
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