Pure Heart And Safety Into Account Capsule Anxiolytic Effects Pharmacodynamics And Mechanism

Anxiety is perceived as an unpleasant affect, characterized by a tense and physically exhaustion, focused on an impending and inevitable sense, although not objectively apparent, danger or emergency along with a painful awareness of uncertainty about the possibility of resolving the situation. The occurrence of anxiety as a mental disorder is increasing recently. Diazepam, as an widely used anxiolytic, has serious side effects, such as sedation,hypnosis,muscle relaxation, tolerance ,withdrawn effect, and so on. As the traditional Chinese medicine (TCM) is well known as their little side effect, we studied a new Chinese herb preparation QingXin AnLu Capsule (QX) which have the actions of soothing the liver and relieving the stagnation of liver-qi, clearing heat and resolving phlegm, and nourishing the heart and anchoring the gallbladder. 1.Literature Review: We had reviewed anxiety-related literature in home and abroad, including the following aspects: general situation of anxiety in TCM and western medicine; development of anti-anxiety TCM and animal models. 2. Experimental Study 2.1 Pharmaceutical research Experiment 1,2: According to the differences between water-solubility ingredient and lipid -solubility ingredient and their different actions, we studied the distilling technics, and fixed on the concentrating, drying and molding technics. Furthermore, we studied the quality standards and principium stability. It reveals that the preparation is qualified and stability. 2.2 Pharmacodynamics and toxicology research 2.2.1 Pharmacodynamics research Experiment 3-6: According to elevate plus maze test in mouse, QXⅠ-Ⅲ groups (0.3g/Kg, 0.6g/Kg, 1.2g/Kg) can increase the open entries percent(OE%) and open times percent (OT%)significantly, while the effect of QXⅣ(2.4g/Kg) is not better than QXⅢ's(1.2g/Kg). The anti-anxiety effect of QX in the light-dark box test is similar to the result of EPM. In the test of pentylenetetrazole (PTZ) induced seizure in mice, QX can significantly decrease the death rate of mouse compared with the control group, while has little effect on the seizure latency. It reveals that QX has a relaxative anti-convulsion effect. Experiment 7-9: The result of EPM in rats also verified that QX had a stable antianxiety effect without increasing the activity of the animal. Vogel's conflict test suggested that QX Ⅱ , Ⅲ groups significantly increased the number of licks during the punished period comparing with control group(P<0.05). In PTZ discsimination test, QXⅡ,Ⅲ groups could significantly decrease the right PTZ discrimination rate, and the antianxiety effect was dose and time dependent. 2.2.2 Acute toxicity research Experiment 10: Preliminary experiment showed that the maximally tolerated dose(MTD)of QX is 16.2g/kg. It is 216 times as clinical dose. The result revealed that QX Capsule is safe. 2.3 Mechanism approaches 2.3.1 Effects of QX on the GABA pathway in different model Experiment 11: RT-PCR was used to analyze the effects of QX on GABAA-α2 receptor mRNA expression in hippocampus of PTZ discrimination model rats. The result showed that GABAA-α2 receptor mRNA expression level could be increased by diazepam and QX. Experiment 12: Use the ISH (in situ hybridization histochemistry) technique to analyze the effects on DBImRNA expression of immobilization stress in rats. The DBImRNA expression level and positive cells of model group had elevated significantly. Compared with model group, the number of positive cells significantly decreased in DZP and QXⅡ group. Experiment 13: Use the Radioimmunoassay technique to detect the content of progestin, the result showed that QX did not influence the progestin content in serum, while it could increase the content of progestin in cortex. Based on the above experiments, we can draw a conclusion that QX can elevated the expression level of GABAA-α2 receptor mRNA, inhibit the DBImRNA expression and increase the content of progestin in cortex to influence the GABA pathway to play a role in anti-anxiety. 2.3.2 Effects of QX on the monoamines i...