Moss Black Phenolic Glucoside In Rats Of Different Body State Pharmacokinetics And Organizational Distribution Of Differences In Study

Background:The study is a part of "Essential study of the property of TCM base on three factors theory", which is supported by the Major State Basic Research Development Program of China (National Project 973) (No.2007CB512605). A hypothesis is proposed that the property of TCM derives from its bioactivity, which is related to the status of organism and chemical constituents. Therefore, the status of organism, chemical constituents and bioactivity are considered to be three factors of the property of TCM. The organism plays a role in expression of bioactivity of drugs. The body in different states processes the drug differently, resulting in different biological effects. Orcinol glucoside has been identified as component absorbed in plasma of curculiginis rhizome that is pungent in taste and hot in nature. This study is searching for the differences of orcinol glucoside's absorption, distribution and elimination rates in rats of asthenia cold, normal and asthenia hot by means of pharmacokinetic (PK) method, and focus on mechanism of bioactivity of drugs in different organism states.Aim:To study the differences of orcinol glucoside's absorption, distribution and elimination processes in rats of Yang-deficiency, normal and Yin-deficiency, provide some experimental basis for the mechanism of bioactivity of drugs in different organism states.Methods:Experiment I:Thirty-six SD male rates were randomly divided into normal group, Yang-deficiency group induced by hydrocortisone, and Yin-deficiency group induced by dexamethasone. Water extraction of curculiginis rhizome was administered to rats by intragastric administration once at 20g crude drug·kg-1 doses and then blood samples were obtained from fossa orbitalis at eleven time points. All the plasmas concentrations were analyzed by HPLC diode array detector after removal of proteins by methanol and other treatments, and Concentration-time data was treated by DAS2.1.1 software.ExperimentⅡ:Sixty SD male rates were also randomly divided into normal, Yang-deficiency, and Yin-deficiency group. On the basis of the experimentⅠ, the rats were killed seperately at 20min (during absorption Phase),50min (during equilibrium Phase), 90min and 180min (during elimination Phase) post dose, liver and kidney were removed at once. The tissue concentrations were analyzed by HPLC diode array detector after cleaning, homogenation, proteins removal, etc.Results:Experiment I:The concentration-time curves of orcinol glucoside in all the three groups fitted open one compartment model by fitting the Concentration-time data using DAS2.1.1 software. In normal, Yang-deficiency and Yin-deficiency rats, Cmax (mg/L) were 16.15±4.13,15.42±1.86,20.08±4.44; Tmax (min) were 48±27,46±32,38±16; AUC(0-t) (mg/L*min) were 2017.748±222.517,2355.246±300.729,2130.231±233.724; t1/2 (min) were 126.396±142.32,102.115±60.006,63.454±28.925; CL/F (L/min/kg) were 0.027±0.011,0.025±0.005,0.032±0.002; MRT(0-t) (min) were 94.336±28.545,96.069±10.634,84.245±17.131; V1/F (L/kg) were 3.329±2.046,3.379±1.076,2.928±1.334. ExperimentⅡ:The content of orcinol glucoside was higher in kidney tissue than in others. Among the three group rats, it is significantly different in the absorption Phase and equilibrium Phase in kidney with the order CYin-deficiency>CYang-deficiency>Cnonnal; and in the elimination Phase in liver with the order CYang-deficiency>Cnormal>CYang-deficiency. Conclusion:The orcinol glucoside's volume absorbed by Yang-deficiency rats is biggest, absorbed faster and eliminated slower; while the volume absorbed by Yin-deficiency rats is samallest,absorbed slower and eliminated faster. The organism status has significantly affected orcinol glucoside's PK characteristics and distribution in liver and kidney tissues. It is speculated that activity of drug-related metabolic enzymes has changed because of Yang-deficiency and Yin-deficiency states, which led to the changes.