Experimental Studies On The Pharmacodynamic Effect Of Xiangshao Capsules

Xiangshao capsules,consisting of 10 herbs,such as Baishao and Xiangfu,is a new form drugs improved from Xiangshao particles,a listed species of a pharmaceutical group.It can suppress the liver,regulate qi and relieve distention and pain,assisting to harmonize the stomach.The indications of this new drugs are mainly premenstrual syndrome,which manifests many symptoms concluding premenstrual irritability, breast tenderness,headache,insomnia,abdominal pain,epig-astric pain,nausea and vomiting,and menopausal syndrome.In this thesis,based on the pharmacodynamic studies of Xiangshao particles,we evaluated the Xiangshao capsules' pharmacodynamics effect from its function and indications. Two animal disease model were used in this study:the models of premenstrual syndrome which is evaluated by Analgesic antispasmodic (writhing, uterine smooth muscle spasm experiment in vivo), sedative -hypnotic (impact on sleep time of threshold dose of sodium pentobarbital and spontaneous activities),and sound- electrical stimulation combining with social-isolated raise and intrusion in rat;the models of menopausal syndrome which is evaluated by Analgesic antispasmodic, sedative-hypnotic, and the influence on hypothalamus - pituitary - ovarian axis of aging female.Using the two animal models,we objectively evaluated the main characteristics and efficacy about Xiangshao capsules,which will provide references for it's clinical studies. The main ways and results of this study are as follows:1. Analgesic antispasmodic effects:The acetic acid-induced writhing response times was reduced by 6.6,13.2g/kg of Xiangshao capsules.The degressive frequency of uterine contractions by oxytocin was increased after giving 2.75,5.50,11.00g/kg of Xiangshao capsules.The degressive tension and peak are of uterine contractions by oxytocin was increased after giving 5.50,11.00g/kg of Xiangshao capsules.2. Sedative and hypnotic effects:The number of stangding time was reduced after giving 3.3,6.6 and 13.2g/kg of Xiangshao capsules 30 and 60 minutes.The sleeping time was extended under the threshold dose of pentobarbital sodium in mice by 3.3,13.2g/kg of Xiangshao capsules.3. The effects on the rat model of sound-electrical stimulation combining with social-isolated raise and intrusion of premenstrual syndrome(PMS):The lever of GnRH, LH, PRL were increased by 11.00g/kg of Xiangshao capsules.The lever of FSH was decreased by 5.50 and 11.00g/kg of Xiangshao capsules. The lever of P was increased by 2.75 and 11.00g/kg of Xiangshao capsules.The lever of 5-HT and NE were improved by 11.00g/kg of Xiangshao capsules.The uterus coefficint was increased by 11.OOg/kg of Xiangshao capsules.The ovary coefficint was improved by 2.75,11.OOg/kg of Xiangshao capsules.The preputial gland coefficint was improved by 2.75g/kg of Xiangshao capsules.The expression level of 5-HT receptors expression in rat hypothalamus was increased by 11.OOg/kg of Xiangshao capsules.The expression level of GABAB1,GABAB2 receptors expression in rat hypothalamus were increased by 5.50 and 11.OOg/kg of Xiangshao capsules.The expression level of 5-HT,GABAB1,GAB AB2 receptors expression in rat hippocampus were improved by 11.00g/kg of Xiangshao capsules.The expression level of 5-HT,GABAB2 receptors expression in rat frontal region were improved by 5.50 and 11.OOg/kg of Xiangshao capsules.The expression level of GABAB1 receptors expression in rat frontal region was increased by 11.00g/kg of Xiangshao capsules.4. The effects on hypothalamus - pituitary - ovarian axis of older female rats:Compared with the model group, the lever of GnRH,PRL,E2,P were improved by 11.OOg/kg of Xiangshao capsules. The lever of GnRH,P were improved by 5.50g/kg of Xiangshao capsules. The thymus coefficient was improved by 11.OOg/kg of Xiangshao capsules.The uterus coefficient was improved by 2.75g/kg of Xiangshao capsules.The lever of 5-HT and NE in brain homogenate were improved by 2.75,11.00g/kg of Xiangshao capsules. The lever of 5-HT in brain homogenate was increased by 5.50g/kg of Xiangshao capsules.The lever of SOD in serum was increased by Xiangshao capsules. The expression level of 5-HT receptors expression in rat hypothalamus was increased by 11.00g/kg of Xiangshao capsules.The expression level of 5-HT,GABAB2 receptors expression in rat hippocampus were improved by 11.00g/kg of Xiangshao capsules.The expression level of 5-HT receptors expression in rat hippocampus was improved by5.50g/kg of Xiangshao capsules.The expression level of GABAB1 and GABAB2 receptors expression in rat frontal region were improved by 11.OOg/kg of Xiangshao capsules.In summary,these studied results indicate that Xiangshao capsules have inhibitory effect on acetic acid-induced writhing and the spontaneous activities of mice under the experiment dosage range. Xiangshao capsules have a role in reducing the independent tension for rat uterus and have impact on prolonging sleeping time under thethreshold dose of sodium pentobarbital. Additionally, Xiangshao capsules have effect on improving sex hormones and neurotransmitters in the rats model of premenstrual syndrome and the older female rats.For PMS and menopausal syndrome,the main mechanisms of action of the new drugs may be related to not only the regulation of hypothalamus -pituitary - ovarian axis and neurotransmitters but also 5-HT,GABAB1,GABAB2 receptors expression in different brain regions.