The purpose of this study was to prepare the nobiletin-loaded nanoemulsions (NOB-NE) and study its in vivo distribution in mice. The characteristics and stability of the unloaded and drug-loaded nanoemulsions were investigated. The size, apparent viscosity and pH value of NOB-NE were respectively (15.5 +/- 2.9) nm, (3.10 +/- 0.33) mPa x s and 6.56 +/- 0.05, which were all higher than those of unloaded nanoemulsions. The zeta potential of unloaded and drug-loaded nanoemulsions carried negative charge. The NOB-NE after diluted by 5% glucose solution was stable in 8 h, and there was no significant difference in the size, content and diluted stability of its preconcentrate in long-term storage. The concentration of nobiletin in plasma and tissues was determined by HPLC after intravenous administration of NOB-NE. Based on AUC(0-t), MRT and C(max), the nanoemulsions delivered more nobiletin into the brain and kidney compared to those of nobiletin solution. The brain and kidney targeting efficiency was improved. In addition, the results fitting using SAAM II software show that the higher drug concentration of the NOB-NE in the brain might be owed to the quicker transport rate from the blood to the brain, and that in the kidney relate to the probable accumulation effect. These results indicate that the in vivo distribution of NOB-NE with consistent quality in mice could be changed and its brain and kidney targeting absorption capability was enhanced comparing with nobiletin solution.
Animals ; Drug Stability ; Emulsions ; Female ; Flavones ; administration & dosage ; pharmacokinetics ; Male ; Mice ; Nanoparticles ; administration & dosage ; Tissue Distribution

Athletes ; Flavones/administration & dosage* ; Humans ; Hydrocortisone/blood* ; Seasons ; Sports Nutritional Physiological Phenomena ; Testosterone/blood* ; Whey Proteins/administration & dosage*

OBJECTIVETo investigate the intestinal absorption of naringin, hesperidin, neohesperidin and the extract of Fructus Aurantii Immaturus in rats.

METHODThe rat intestinal perfusion and enzymes incubation models were used, together with the determination of the n-octanol/water partition coefficient of the components (P).

RESULTIn perfusion model, the P(eff) of all components were low, and the P(eff) of naringin, hesperidin and neohesperidin were 0.140-0.252, 0.156-0.268 and 0.154-0.285, respectively. In four different regions of intestine of rat and with different concentration, the P(eff) of the components both had no significant difference, whereas the P(eff) of the extract were higher than the P(eff) of the single component. The metabolite of components was not detected in intestine. The P of naringin, hesperidin and neohesperidin were 0.36, 0.40 and 0.48, respectively, and the pH of buffer solution had no influence to its distribution coefficient.

CONCLUSIONPoor permeation contributed to the poor intestinal absorption of naringin, hesperidin and neohesperidin. The absorption of components in extract were increased, and the results suggest that the extract may enhance the intestinal absorption of the components.

Animals ; Citrus aurantiifolia ; chemistry ; Flavones ; administration & dosage ; Fruit ; chemistry ; Intestinal Absorption ; drug effects ; Male ; Plant Extracts ; administration & dosage ; Rats ; Rats, Sprague-Dawley

To prepare self-assemble nobiletin proliposomes and study its pharmacokinetic behavior in rats after ig administration, and nobiletin suspension was used as control, self-assemble nobiletin proliposomes were prepared by a new proliposome preparation method, their physicochemical properties including encapsulation efficiency, particle size and stability of formed liposome were determined. Plasma concentration of nobiletin was determined by HPLC taking nimodipine as internal standard. The pharmacokinetic parameters were calculated by Kinetica 4.4 software. The encapsulation efficiency of nobiletin liposomes was more than 80%, with an average particle size of 212.1 nm and very good stability. Compared to nobiletin suspension, nobiletin liposomes possessed higher absorptive rate and longer MRT, and the relative bioavailability was 264.3% in rats. It could be concluded that self-assemble nobiletin proliposome was a simple and feasible preparation, and showed greater absorption compared with nobiletin suspension.
Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Drug Carriers ; Drug Stability ; Flavones ; administration & dosage ; blood ; pharmacokinetics ; Lecithins ; chemistry ; Liposomes ; chemistry ; Male ; Particle Size ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study drug release of sustained-released tablets of total puerariae flavones and investigate the evaluating method of sustained released preparations Chinese material medica sustained-released preparation.

METHODRotating basket method and HPLC were employed to assess the characteristics of multi-component.

RESULTUnder the selected chromatographic conditions, good HPLC fingerprint of the release of sustained-released tablets of total puerariae flavones were obtained. Through the determination of 8 time-point samples,the release of sustained-released tablet of total puerariae flavones had a well-balanced release behavior.

CONCLUSIONThe HPLC-UV fingerprint method was simple and reproducible, quality of tablets of total puerariae flavones can be controlled effectively by the method. The method could be applied to evaluate the release of sustained-released tablets of total puerariae flavones.

Chromatography, High Pressure Liquid ; Delayed-Action Preparations ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; metabolism ; Flavones ; chemistry ; metabolism ; Pueraria ; chemistry ; Reproducibility of Results ; Tablets

In this study, metabolism of nobiletin in rats was studied using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). As a result, seven major metabolites were found in bile, urine and serum of rats. Three phase I products were assigned to be demethyl and di-demethyl products, and other four phase II products were assigned to be glucuronic and sulfonic conjugates. The four phase II metabolites were reported for the first time. Among the metabolites found in the present study, the glucuronic conjugates of demethyl-nobiletin played a predominant role in the metabolic pathway, indicating that its potential role for glucuronidation-related factors, such as gene polymorphism, drug-drug interaction, etc., in changing the active and toxic effect of nobiletin and that it should be paid more attention in further development.
Administration, Oral ; Animals ; Antioxidants ; administration & dosage ; metabolism ; Bile ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Flavones ; administration & dosage ; blood ; metabolism ; urine ; Male ; Mass Spectrometry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

The goal of the study is to evaluate the self-microemulsifying drug delivery system (SMEDDS) which enhances the oral bioavailability of the poorly water-soluble drug, total flavones of Hippophae rhamnoides (TFH). It is orally administered for the protection of human cardiovascular system. Self-microemulsifying time, particle size, polydispersity index (PDI), morphological characterization, in vitro dispersity, stability, in situ intestinal absorption and relative bioavailability were investigated in detail. The TFH-SMEDDS rapidly formed fine oil-in-water microemulsions with 0.1 mol x L(-1) hydrochloride solution, with average size of which was less than 40 nm, PDI was below 0.2, and the particles of which were observed round-shaped under transmission electron microscope. Almost 90% of TFH (expressed with quercetin) was released from SMEDDS within 20 min, which was remarkably higher than that from common capsules. The stability test showed the TFH-SMEDDS maintained stable in 6 months under accelerated condition. In situ absorption study demonstrated the absorption rate constant of TFH-SMEDDS (expressed with quercetin) was significantly higher than that of TFH in ethanolic solution (P < 0.05). The absorption of TFH from SMEDDS showed a 4.18-fold increase in relative bioavailability (expressed with quercetin) compared with that of the suspension. The results suggest that SMEDDS is a promising drug delivery system to increase the oral bioavailability of TFH.
Administration, Oral ; Animals ; Biological Availability ; Drug Carriers ; Drug Delivery Systems ; Emulsions ; Flavones ; administration & dosage ; isolation & purification ; pharmacokinetics ; Fruit ; chemistry ; Hippophae ; chemistry ; Intestinal Absorption ; Male ; Particle Size ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the effect of total flavones of Epimedium leptorrhizum (YYH-C) on osteoporosis in ovariectomized rats.

METHODOvariectomized female rats were randomly divided into the model group, YYH-C lower, middle and high dose (0.7, 1.4, 2.8 g x kg(-1)) groups, the positive drug Bujiale (0.15 mg x kg(-1)) group, and the sham group. The rats were orally ad-ministrated with drugs for three months. Parathyroid hormone (PTH), procollagen I N-terminal peptide (PINP), alkaline phosphatase (ALP), calcium (Ca) and phosphrous (P) in serum were detected. Femur bones and vertebrae bones of left side were collected to determined bone metrological indexes, including bone mineral density (BMD), bone Ca, and bone ash weight/dry weight percentage. Femur bones of right side were collected to for a morphological observation of bone.

RESULTCompared with the sham group, the model group showed significantly higher PTH and ALP content but obviously lower PINP and Ca content. The three YYH-C 3 groups could resist the decrease of PINP. Specifically, low and middle dose groups could remarkably inhibit the increase of PTH, and the high dose group could increase the Ca content in serum, but without significant effect on the rise in ALP. There was no significant difference in P content in serum in each group. BMD, ash weight/dry weight percentage, Ca and P content of the model group were significantly lower than those in the sham group. The high dose YYH-C group could significantly increase BMD. All of the three YYH-C groups could notably increase ash weight/dry weight percentage and Ca, P content in femur bones and vertebrae bones. YYH-C could significantly increase average thickness, area, area percentage of bony trabeculae, cortical bone area percentage of femoral shaft and the number of osteoblasts on the surface of bony trabeculae, and decrease the number of osteoclasts.

CONCLUSIONYYH-C can effectively control the bone mass loss of rats with ovariectomy-induced osteoporosis, prevent the changes in bone microstructure, and inhibit bone absorption, so as to resist high turn-over osteoporosis after ovariectomy. [Key words] total flavones of Epimedium leptorrhizum; ovariectomized rat; osteoporosis

Alkaline Phosphatase ; metabolism ; Animals ; Bone Density ; drug effects ; Calcium ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Epimedium ; chemistry ; Female ; Flavones ; administration & dosage ; Humans ; Osteoporosis, Postmenopausal ; drug therapy ; metabolism ; physiopathology ; Ovariectomy ; Parathyroid Hormone ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the effects of total flavone of Abelmoschl Manihot L. Medic (TFA) on the function of platelets and to explore its mechanism.

METHODSRat models of artery-veins bypassing thrombus formation were used. The platelets of rabbits were collected. Platelet aggregation was induced by collagen and intracellular calcium ion concentration ([Ca(2+)]i) was assayed by Fura-2 method.

RESULTSTFA (25, 50, 100 mg/kg) significantly and dose-dependently reduced the weight of thrombus. TFA (0.025, 0.05, 0.1 mg/ml) possessed dose-dependant inhibitory effects on rabbits' platelet aggregation induced by collagen. TFA significantly reduced the resting and CaCl(2)-induced increase of free intracellular calcium concentration ([Ca(2+)]i) in rabbit platelet in vitro.

CONCLUSIONTFA has an antiplatelet effect via the inhibition on the influx of Ca(2+).

Animals ; Blood Platelets ; drug effects ; Calcium ; blood ; Calcium Channel Blockers ; administration & dosage ; pharmacology ; Calcium Chloride ; pharmacology ; Carotid Artery Thrombosis ; blood ; etiology ; Collagen ; pharmacology ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Flavones ; administration & dosage ; pharmacology ; Glycosides ; administration & dosage ; pharmacology ; Intracellular Membranes ; metabolism ; Osmolar Concentration ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; administration & dosage ; pharmacology ; Platelet Function Tests ; Rabbits ; blood ; Rats ; Rats, Wistar

OBJECTIVETo study the impact of total flavones from Artemisia anomala (TFAS) on activation of macrophages, cell oxidative stress, auto-nitration of CuZn-SOD, platelet aggregation and isolated vascular tension.

METHODLPS and IFN-gamma induced activation of macrophages and oxidative stress in rats; H2O2 and nitrite induced auto-nitration of CuZn-SOD; ADP, AA and collagen induced platelet aggregation in vitro in mice; PE stimulates isolated vascular tension; nitrite content of macrophages was measured by Griess assay; MTT assay and FRAP assay was applied for cell viability and total cell antioxidant capacity; auto-nitration of CuZn-SOD was measured by Western blot and colorimetric methods; platelet aggregation was detected by turbidimetry; and aorta ring relaxation was recorded by isolated vascular function experience devices for rats.

RESULTTFAS demonstrated dose dependence (25, 50, 100, 200 mg x L(-1)) on inhibiting induced macrophages NO production from generating, while increasing cell viability and total anti-oxidant capacity. Auto-nitration of CuZn-SOD was suppressed by TFAS in dose dependence (0.5, 5, 50 mg x L(-1)). TFAS showed an inhibitory effect on collagen-induced platelet aggregation at 50 mg x L(-1) and an endothelium-dependent relaxation effect on PE-induced vasoconstriction at 1 g x L(-1).

CONCLUSIONTFAS shows effect on anti-inflammation, anti-oxidation, anti-nitration, anti-platelet aggregation and vasodilatation in experiment in vitro, which may inhibit vascular inflammatory by regulating multiple target points. It is among material bases for promoting blood circulation and removing blood stasis.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Aorta ; drug effects ; immunology ; physiology ; Artemisia ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Flavones ; administration & dosage ; Humans ; Macrophages ; drug effects ; immunology ; Mice ; Oxidative Stress ; drug effects ; Rats ; Vasodilation ; drug effects