| Chrysophanol is an anthraquinone compound monomer from rhubarb. The previous studies confirmed that chrysophanol could significantly reduce lipid peroxide formation in the liver and brain of rats, and showed anti-aging effects. At present, the perpration process of chrysophanol polybutylcyanoacrylate nanocapsule, chrysophanol hydroxypropyl-β-cyclodextrin inclusion compound and chrysophanol liposomes three formulations have been finished by our research group. In order to compare the differences of the tissue distribution in vivo of the chrysophanol three formulations, the tissues and plasma in mice were taken according to different time with the different formulations of the same dose by trail intravenous injection. The tissues distribution of the chrysophanol was measured by using high performance liquid chromatography. And then the impairment model of mice was prepared by injecting the scopolamine,the model of cerebral ischemia reperfusion was prepared and the Alzheimer’s disease (AD) model was prepared by the injection of β-amyloid peptide (beta-amyloid peptide fragment25-35, Aβ25-35) only once at lateral ventricle. The chrysophanol formulation of the most significant brain tissue targeting were injected respectively, and the study on pharmacodynamics of the chrysophanol formulations would improve futher. At the same time,the optimum dose was chosen, and the a good foundation will be offered for clinical application for the future.1Tissue distribution of three chrysophanol formulations 144male mice were divided into twenty-four groups randomly, chrysophanol [N,N-Dimethylformamide (DMF) dissolved] and three kinds of chrysophanol formulations solution were taken with the same dose of10mg-kg-1by trail intravenous injection in each six groups. Administration of drug in0.25,1,2,4,8,12h, samples of plasma and tissue were taken. The content of the chrysophanol on plasma and tissue were measured by high performance liquid chromatography. And the drug concentration of drug were calculated.Results showed that the tissue distribution of three kinds of chrysophanol formulations were wider than chrysophanol DMF solution of tissue distribution with doses of10mg-kg-1by trail intravenous injection, and higher content in brain and liver tissue distribution.They could be easily transported through the blood brain barrier and could reduce the distribution of the heart and kidneys, and can increase the duration of drug action in the body. Chrysophanol liposomes is the most significant formulations of tissue distribution.2Pharmacodynamic experiment of chrysophanol liposomes220male mice were divided into twenty-four groups randomly:Group1were normal control group, scopolamine induced memory impairment model group, chrysophanol liposomes solvent control group, chrysophanol DMF group (10mg·kg-1), chrysophanol liposomes groups (10,1,0.1mg·kg-1); Group2were normal control group, sham-operated group, cerebral ischemia reperfusion modal group, chrysophanol liposomes solvent control group, chrysophanol DMF group (10mg·kg-1), chrysophanol liposomes groups (10,1,0.1mg·kg-1); Group3were normal control group, AD modal group, chrysophanol liposomes solvent control group, chrysophanol DMF group (10mg·kg-1), chrysophanol liposomes groups (10,1,0.1mg·kg-1). The appropriate drug or solvent were administered injection for each group of mice. And each group of mice had behavioral experiments of Y-maze and step down test. After the behavioral experiments, decapitated and taken blood, at the same time the number of were recorded mouth open and decapitation hypoxia tolerance survival time.Preparation of tissue samples, with spectrophotometric detection of liver, brain malondialdehyde (MDA) content, of liver, brain tissue superoxide dismutase (SOD) activity,of liver glutathione peroxidase (GSH-Px) inactivity, the activity of brain tissue cholinesterase (ACh), of brain, liver organized activity of catalase (CAT); fluorescence spectrometry of brain tissue lipofuscin (LF) content.Results showed that all of these three models could cause significant memory impairment in mice (P<0.01), the survival of the mice were decapitated and hypoxia tolerance time and the number of mouth breathing were significantly reduced (P<0.05), brain, liver, plasma the activity of CAT, GSH-Px and SOD were decreased (P<0.01), MDA contents in brain and liver tissue rising (P<0.01), increased AChE and LF content of brain tissue (P<0.01). Compared with the corresponding model group, chrysophanol DMF and high, medium are of two different doses of liposomes have varying degrees of improvement (P<0.05-P<0.01). But low dose group of liposome on these indicators did not significantly improve (P>0.05).These results showed, among these chrysophanol formula-tions,chrysophanlol liposomes was the most widely and highest concentration in brain. Study on the pharmacodynamics of chrysophanol liposomes though experimental learning and memory behavior, and oxidative enzyme activity and metabolite content determination and decapitation hypoxia tolerance experiments. The results showed that chrysophanol liposome can improve the scopolamine-induced memory impairment and cerebral ischemia-reperfusion injury, can reduce a neural toxicity of Aβ25-35.Chrysophanol liposome enhance antioxidant ability of organizations though reduce tissue MDA, LF content, increase of CAT, GSH-Px and SOD activity. Chrysophanol liposome aslo can enhance cholinergic function though inhibition of AChE activity in brain tissue, enhance the hypoxic tolerance of brain tissue, improve cerebral ischemia-reperfusion injury. Therefore the chrysophanol liposomes is expected to become the clinical application of new formulations for clinical treatment. |
PDF Full Text Request