55 population doubling, PD) were compared with those of the young cells(

To explore the mechanism of the absorption of flavonoids from Abelmoschus manihot flowers, in situ intestinal recirculation was performed to study the effect of the absorption at different concentrations and different intestinal regions. To evaluate the conditions of the absorption of six flavonoids from Abelmoschus manihot flowers, the concentrations of Abelmoschus manihot in the perfusion solution were determined by HPLC at predesigned time. And we have investigated the inhibitory effect of six flavonoids from Abelmoschus manihot flowers on P-glycoprotein (P-gp) drug efflux pump. The results demonstrated that the absorption rates of flavonoids from Abelmoschus manihot flowers are not significantly different (P > 0.05) at various drug concentrations, the absorption of flavonoids from Abelmoschus manihot flowers is a first-order process with the passive diffusion mechanism. The absorption rates of each of flavonoids are significantly different. The absorption rate of flavonoid glycoside was lower than that of aglycone; the flavonoids from Abelmoschus manihot flowers could be absorbed in all of the intestinal segments. The best parts of intestine to absorb hyperoside and myricetin are jejunum and duodenum, separately. Verapamil could enhance the absorption of isoquercitrin, hyperoside, myricetin and quercetin-3'-O-glucoside by inhibiting P-glycoprotein (P-gp) drug efflux pump.

The combination of Angelicae sinensis Radix (Danggui, DG) and Astragali Radix (Huangqi, HQ) is a popular herb pair commonly used in clinic for the treatment of blood deficiency syndrome in China. The aim of this paper is to study the interaction of DG and HQ nourishing and tonifying blood effects by response surface method. The blood deficiency mice were induced by injecting N-acetylphenylhydrazine (sc) and cyclophosphamide (ip). The blood deficiency mice were administrated intragastrically with DG-HQ extracts (0:1, 1: 5, 2:5, 2:3, 1:1, 3:2, 5:2, 5:1, 1:0). The changes of the peripheral blood indexes and organ indexes were observed. The indexes were integrated by comprehensive index method; the interactions of DG and HQ were analyzed by the response surface diagram established with Matlab software. The results showed that DG and HQ at most of their combination ratios had synergic effect. Within the range of 1:5 - 5:1, all of the extracts of DG-HQ showed synergic effect, and among which, high-doses had better effects than low-doses. The highest value (-1) of the synergic effect was showed when DG was 10 - 40 g at the same time of HQ as 90 -180 g, and DG was 50 - 100 g at the same time of HQ as 20 - 100 g. DG-HQ at all combination dosages within Chinese Pharmacopeia (DG: 6 - 12 g, HQ: 9 - 30 g) had certain synergic effect, and Danggui Buxue Decoction (DG: 6 g, HQ: 30 g) also was at this range. The results provided scientific basis to the clinical application of DG and HQ. And the response surface method was firstly applied to quantitatively evaluate the bio-activity change of herb combination, which provided a novel way for modern basic research on the interaction of herbs.

Aim To observe the differences of tonify-ing blood effect for the combination of Danggui and Honghua ( GH) with different proportions on blood de-ficiency mice, and choose the proportion of GH which has the optimal tonifying blood effect. Methods The blood deficient mice model was induced by injection of phenylhydrazine and cyclophosphamide. On the basis of multi-attribute comprehensive index method, the op-timal dose was determined through three doses of GH 1: 1 , which was the highest frequency proportion of GH used in the “Dictionary of Chinese Medicine Prescrip-tions”. According to the optimal dose, the change reg-ulation of tonifying blood effect of GH with different proportions was observed. Results Among three do-
ses (1, 3 and 5 times of clinical dose), the tonifying blood effect of GH was best when the dosing concentra-tion of GH was clinical dose. Among nine proportions (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1), GH 1 : 1 had the best effect. Conclusion The results are consistent with regulations of medi-cine usage that GH 1 : 1 has the highest frequency used in Herbal Formulae, which could provide scientif-ic basis for more effective application of Danggui and Honghua in modern clinic medicine.

AIM:To study the influence of material and configuration of microfiltration membranes on preparation of mono-ammonium glycyrrhizinate liposome(MGL) by membrane extrusion. METHODS: MGL were preparated by conventional rotary-evaporated film dispersion method and sonication,and MGL were extruding through 9 kinds of microfiltration membranes with 3 kinds of aperture specs of 0.1,0.2,0.45 ?m.The methods were evaluated by the filtration efficiency and the leakage rate of drug from liposomes. RESULTS: MGL were easily extruding through microfiltration membranes of NY6,PTFE,PVDF,PP and PC.MGL could not extruding through microfiltration membranes of PES,CN,CA and CA-CN.MGL become hardly to extrude through microfiltration membranes when increasing in the concentration of liposomes or the content of cholesterol.The leakage rate of drug from MGL was small when extruding through microfiltration membranes. CONCLUSION: The material and configuration of microfiltration membranes can remarkably influence the preparation of MGL by membrane extrusion method,and PC microfiltration membrane was selected.

The combination of Danggui and Honghua (GH) is a popular herb pair commonly used in clinic for the treatment of blood stasis syndrome in China. To evaluate the activating blood circulation and dissipating blood stasis effects of the combination of different proportions of Danggui and Honghua on acute blood stasis rats, and optimize the proportion of GH to have the best activating blood circulation and dissipating blood stasis effect. Acute blood stasis rat model was induced by subcutaneous injection of adrenaline and ice water bath. The blood stasis rats were administrated intragastrically with GH (1 : 0, 4 : 1, 2 : 1, 3 : 2, 1 : 1, 2 : 3, 1: 2, 1 : 4 and 0 : 1) extracts. The whole blood viscosity (WBV), plasma viscosity (PV), and high shear whole blood relative index (HSWBRI), low shear whole blood relative index (LSWBRI), and erythrocyte aggregation index (EAI) were tested to observe the effects of GH on hemorheology of blood stasis rats. And the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of GH on platelet aggregation index of blood stasis rats. In addition, the prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and plasma fibrinogen (FIB) were tested to observe the effects of GH on blood coagulation function of blood stasis rats. Then principal component analysis and multi-attribute comprehensive index methods were both used to comprehensively evaluate the total activating blood circulation and dissipating blood stasis effects of GH. The results showed that the hemorheological indexes and coagulation parameters of model group both had significant differences with normal group. Compared with model group, GH (1 : 0, 4 : 1, 2: 1, 3 : 2, 1 : 1, 2 : 3, 1 : 2, 1 : 4 and 0 : 1) could improve all the blood hemorheology indexes and regulate part indexes of blood coagulation function and platelet aggregation in acute blood stasis rats. Based on principal component analysis and multi-attribute comprehensive index methods, GH 1 : 1 and GH 3 : 2 both had the best effect of blood circulation and dissipating blood stasis, and the effect of GH 1 : 1 was slightly better than GH 3 : 2. These results suggest that GH could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats. The optimized proportion of GH was consistent with regulations of medicine usage that GH 1 : 1 had the highest frequency used in traditional Chinese formulae. It could provide scientific basis for more effective application of the compatibility between Danggui and Honghua in modern clinic medicine.

The metabolic effect of Fo-Shou-San on blood deficiency mice was studied by using metabolomic method. UPLC-QTOF/MS was used to analyze the plasma metabolome in blood deficiency mice. MS data were processed by MarkerLynx software. With multivariate statistical analysis of plasma metabolite profiles, a clear separation among control, blood deficiency model, and Fo-Shou-San groups was achieved. Potential biomarkers were selected according to the parameters of variable importance in the projection (VIP) and identified according to MS information and database retrieval. The metabolic network of blood deficiency was predicted via MetPA database. Twenty-two potential biomarkers were identified and used to explain the thiamine metabolism, arachidonic acid metabolism, sphingolipid metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, nicotinate and nicotinamide metabolism, cysteine and methionine metabolism, tryptophan metabolism, starch and sucrose metabolism, tyrosine metabolism and citrate cycle (TCA cycle). Those metabolic pathways were disturbed in blood deficiency mice, but which could be regulated nearly to normal state after Fo-Shou-San administration. In this study, the metabolomics of blood deficiency mice and the action mechanism of nourishing blood effect of Fo-Shou-San were evaluated. The physiological and metabolic state of the organism could be represented comprehensively by using metabolomics. And metabolomics can be used to evaluate the pharmacodynamics and related mechanisms of Chinese medicine and formulae.

Object To define suitable gathering season of Ginkgo biloba L. leaves. Methods The content of total flavonoids and total terpene lactones in G. biloba leaves were determined by HPLC DAD and HPLC ELSD. Results The content of total flavonoids and total terpene lactones in G. biloba were distinct in different ages of tree and collecting seasons. Conclusion The content of total flavonoids and total terpene lactones in G. biloba are the highest in 2 3 ages of tree. The total flavonoid is the highest in May and total terpene lactone is the highest in September.

Objective To investigate the effects of quiet respiratory intrathoracic pressure changes on ventricular dimensions and left ventricular systolic function,and to further verify our newly proposed hypothesis of the mechanism of respiratory effects on hemodynamics.Methods Twenty healthy volunteers aged 18 to 40 years average(24?7) years were included.The respiratory curve and electrocardiogram were simultaneously recorded.The interventricular septum movement,ventricular dimensions and ventricular systolic excursions were recorded by two-dimensional and M-mode echocardiography during quiet respiration.The respiratory variations of the above parameters were derived,and the parameters for assessing ventricular systolic function were calculated.Results With quiet respiration,the interventricular septum moved towards the left ventricle on inspiration,and then towards the right ventricle on expiration.The right ventricular diastolic dimension increased significantly on inspiration compared with those on expiration.The opposite changes occurred with left ventricular diastolic dimensions.The left ventricular posterior wall systolic excursion and the left ventricular stroke volume significantly increased during expiration compared with those during inspiration.No significant differences were found in left ventricular ejection fraction and fractional shortening between inspiration and expiration.Conclusions The respiratory intrathoracic pressure change is one of the factors influencing the reciprocal changes of the left and right ventricular parameters related to ventricular dimensions and systolic function.

OBJECTIVETo analyze naringin, naringenin and its metabolites in rat plasma after intragastric administration of exocarpium Citri grandis alcohol extract.

METHODRat blood samples were collected 1.0 hour after oral administration of 50 g x kg(-1) exocarpium Citri grandis alcohol extract and analyzed by UPLC-Q-TOF with MS(E) function. The post-acquisition data were processed using Metabolynx.

RESULTNaringin (M1), naringenin (M2), naringin-5-O-glucuronide (M3), naringin-4-O-glucuronide (M4), glucuronide conjugate of naringenin (M5), naringin-4-O-sulfate (M6), methylated conjugate of hydroxylated naringenin (M7), glucuronide and sulfate conjugate of naringenin (M8), glucuronide conjugate of hydroxylated naringenin (M9) in rat plasma were detected. M3, M4, M6 were first reported as the metabolites of naringin. M7, M9 were first reported as the metabolites of naringenin.

CONCLUSIONThe results indicated that naringin, naringenin can be metabolited as the forms of glucuronidation, sulfation and naringenin can also be metabolited as the forms of methylation with hydroxylation and glucuronidation with hydroxylation in vivo after administration.

Animals ; Chromatography, High Pressure Liquid ; Citrus ; chemistry ; Drug Administration Routes ; Flavanones ; blood ; metabolism ; Male ; Mass Spectrometry ; Plant Extracts ; administration & dosage ; blood ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley