Puerarin is a naturally occurring isoflavone C-glycoside,isolated from the root of Pueraria lobata,which has attracted extensive attention in the medical circles because of its various pharmacological effects,such as vasodilation,cardioprotection,neuroprotection,antioxidant,anticancer,anti-inflammation,alleviating pain,promoting bone formation,inhibiting alcohol intake,and attenuating insulin resistance. However,its low oral bioavailability has limited its clinical application. This review gives a comprehensive summary of the researches on physicochemical properties,pharmacokinetics( absorption,distribution,metabolism and excretion,pharmacokinetic parameters) in oral administration,and pharmaceutics research strategies of puerarin in recent years,and the in vivo behavior difference between multicomponent and single component environment was also summarized. The reasons( low water solubility,poor membrane permeability,short half-life,inhibition of P-gp efflux and first-pass metabolic effects of intestinal enzymes,etc.) for low bioavailability were concluded and the idea that multicomponent enviroment would affect the bioavailability was clarified. The aim of this review is to provide literature basis for the development of new dosage forms and new technologies for multivariate compound drug delivery system to improve the bioavailability of oral puerarin,and to propose ways to improve the bioavailability of BCS Ⅳ drugs derived from traditional Chinese medicine by fully enlarging the synergistic effect of multi-components or reasonably using the inhibitory effect between components.
Administration, Oral ; Biopharmaceutics ; Isoflavones ; Pueraria

To decrease the hemolysis side effect of puerarin, the basic formula and preparation of puerarin submicron emulsion were optimized and the physicochemical properties were evaluated. Puerarin submicron emulsions were prepared by phase inversion-ultrasound combining with phospholipids complexes technology. The effects of preparative parameters, such as emulsification time, stirring velocity and ultrasound time, on mean diameter, span of dispersity, entrapment efficiency and overall desirability were investigated. The three dimensional response surface graphs were produced by second-order polynomial and liner equation, which predict the optimal experiment conditions. All response variables were found to be greatly dependent on three independent variables. Second-order polynomial equations were fitter than liner equations for this study. The optimal emulsification time, stirring velocity and ultrasound time was 15 min, 2 000 r x min(-1), 30 min, respectively. The mean diameter, span of dispersity, entrapment efficiency, drug content and zeta potential of emulsions prepared by the method were 228.23 nm, 0.628 4, 84. 32%, 9.98 mg x mL(-1), - 29.03 mV, respectively. Puerarin submicron emulsion was prepared by the optimized preparation method. The narrow particle diameter distribution, high envelopment efficacy and good stability were obtained. The physicochemical properties were suitable for the requirement of the intravenous emulsion.
Emulsions ; Isoflavones ; administration & dosage ; chemistry ; Particle Size

OBJECTIVETo study the effect of phenformin hydrochloride that may be illegally added in traditional Chinese medicine preparations on the pharmacokinetics of puerarin in rats.

METHODRats were randomly divided into the single pueraria group and the phenformin hydrochloride combined with pueraria group. After oral administration in the two groups, their bloods were sampled at different time points to determine the drug concentration of puerarin in rat blood and calculate pharmacokinetic parameters.

RESULTAfter oral administration with pueraria extracts and phenformin hydrochloride combined with pueraria extracts, the two groups showed main pharmacokinetic parameters as follows: Cmax were (2.39 +/- 1.01), (1.03 +/- 0.35) mg x L(-1), respectively; Tmax were (0.50 +/- 0.09), (1.5 +/- 0.5) h, respectively; Ke were (0.153 +/- 0.028), (0.172 +/- 0.042) h(-1), respectively; t(1/2) were (4.65 +/- 0.86), (4.20 +/- 0.81) h, respectively; AUC(0-t), were (5.73 +/- 2.60), (5.45 +/- 1.81) mg x h x L(-1), respectively; AUC(0-infinity) were (6.72 +/- 2.89), (6.26 +/- 1.88) mg x h x L(-1), respectively. Compared with the single puerarin group, the Cmax was significantly decreased (P < 0.05) and the Tmax was markedly longer (P < 0.01) than the hydrochloride combined with pueraria group.

CONCLUSIONPhenformin hydrochloride can slow down the absorption process of puerarin and change the pharmacokinetic process of puerarin to some extent.

Administration, Oral ; Animals ; Drug Interactions ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Isoflavones ; administration & dosage ; pharmacokinetics ; Male ; Phenformin ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; Vasodilator Agents ; administration & dosage ; pharmacokinetics

The isoflavonol glycoside Talosin A, genistein (GT)-7-alpha-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-beta-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean Cmax of 2.74 microg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being convereted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean Cmax of 0.24 mg/mL at 1.25 h; conjugated GT with a mean Cmax of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.
Actinobacteria/*chemistry ; Administration, Oral ; Animals ; Area Under Curve ; Glycosides/administration & dosage/*metabolism/pharmacokinetics ; Hydrolysis ; Intestinal Absorption ; Isoflavones/administration & dosage/*metabolism/pharmacokinetics ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study pharmacokinetic of puerarin in rats following different methods of administration of Tongqiao Sanyu prescription.

METHODTongqiao Sanyu prescription was administered to rats by caudal vein injection, nasal administration and oral administration. Plasma samples were extracted with methanol and the plasma concentration of puerarin was analyzed by RP-HPLC. The pharmacokinetic parameters and bioavailability were calculated with Kinetica software.

RESULTThe main pharmacokinetic parameters were as follows: AUC(0-infinity) of caudal vein injection was (787.99 +/- 70.44) mg x min x L(-1); AUC(0-infinity) of nasal administration was (376.56 +/- 93.93) mg x min x L(-1); AUC(0-infinity) and oral administration (The dose was decuple higher than that of caudal vein injection and nasal administration) was (491.18 +/- 110.64) mg x min x L(-1). The absolute bioavailability of puerarin was 47.78% by nasal administration and 6.23% by oral administration.

CONCLUSIONThe bioavailability of nasal administration is higher than oral administration significantly, this result can provide some scientific foundantion for the method of administration and the reform of dosage form of Tongqiao Sanyu prescription.

Animals ; Biological Availability ; Drug Administration Routes ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Isoflavones ; administration & dosage ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley

PURPOSE: This study was conducted to explore the relationship between isoflavones intake from soy foods and perimenstrual symptoms among women. METHODS: The research design was a cross sectional study. Subjects consisted of 245 women living in Korea, aged 19-49 years. The measurement tools were MDQ and FFQ. RESULTS: Frequently consumed soy isoflavones foods were rice with soybeans, soybean paste stew, and soy paste with tofu. The amounts of soy isoflavones foods consumed in order from highest to lowest were rice with soybeans, soybean paste stew, seasoned soybean sprouts, and soy paste with tofu. Subjects were divided into three groups by isoflavones intake levels; the small intake group, moderate intake group, and large intake group. There were significant differences in some menstrual symptoms, and postmenstrual symptoms by isoflavones intake levels. In general, the moderate isoflavones intake group showed lower scores in some menstrual symptoms and postmenstrual periods compared to the small and large intake groups. CONCLUSIONS: These results suggest some positive health effects of isoflavones from soy foods on perimenstrual symptoms. More accurate, objective measurement needs to be applied and more investigation of soy isoflavones effects on many aspects of women's health need to be done in a future study.
Adult ; Demography ; Diet Surveys ; Female ; Humans ; Isoflavones/*administration & dosage ; Middle Aged ; Multivariate Analysis ; *Perimenopause ; Questionnaires ; *Soy Foods

OBJECTIVETo investigate the mechanisms of the oil-in-oil nanoemulsions transport through the gastrointestinal tract and the transport efficiency changed with its different particle size in the lymphatic channels.

METHODThe behavior of nanoemulsions in vivo and their absorption via lymph after oral administration was investigated, with the transport efficiency and absorption pathway of nanoemulsions clarified by lymph duct cannulation in rats.

RESULTIt suggested about 36.8% of puerarin nanoemulsions was transported into systematic circulation via lymph. Nanoparticles with different size absorbed by the lymphatic channels varied as the degree of transportion.

CONCLUSIONThe degree of absorption and particle transport is inversely proportional to the size.

Absorption ; Animals ; Biological Transport ; Emulsions ; Female ; Isoflavones ; administration & dosage ; pharmacokinetics ; Lymph ; metabolism ; Male ; Nanoparticles ; Particle Size ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the distribution process of puerarin contained in Zige freeze-dried powder injection in rat liver and kidney and the safety of Zige freeze-dried powder injection.

METHODRats were divided into the Zige freeze-dried powder injection group and the puerarin freeze-dried powder injection control group randomly. The liver and kidney samples were collected at 5, 10, 20, 30, 45, 60 and 120 min after intravenous administration of puerarin (26.7 microg x g(-1)) through caudal vein and detected by HPLC.

RESULTThe concentration of puerarin in kidney reached the max value of 58.12 microg x g(-1) for the Zige freeze-dried powder injection group and 71.28 microg x g(-1) for the Puerarin freeze-dried powder injection group. The value of AUC(0-2h) was 26.24 microg x h x g(-1) for the Zige freeze-dried powder injection group and 35.24 microg x h x g(-1) for the puerarin freeze-dried powder injection group, MRT(0-2h) was 0. 39 h for the Zige freeze-dried powder injection group and 0. 42 h for the puerarin freeze-dried powder injection control group. Compared with the control group, the Zige freeze-dried powder injection group showed a significant decrease in Cmax and AUC(0-2h) (P < 0.05), with no notable difference in peak time tmax and MRT(0-2h). The two groups showed no obvious difference in tmax Cmax, AUC(0-2h) and MRT(0-2h) of puerarin in rat kidney.

CONCLUSIONCompared with Zige freeze-dried powder injection, Zige freeze-dried powder injection can reduce the distribution of puerarin in rat kidney, with no obvious change in the elimination of puerarin in rat kidney. It also showed no significant change in distribution and elimination in liver. This indicates that Zige freeze-dried powder injection is safer to kidney than puerarin freeze-dried powder injection.

Animals ; Freeze Drying ; Injections ; Isoflavones ; administration & dosage ; adverse effects ; pharmacokinetics ; Kidney ; metabolism ; Liver ; metabolism ; Male ; Powders ; Rats

Animals ; Hemorheology ; Isoflavones ; administration & dosage ; pharmacology ; Male ; Pulmonary Artery ; physiopathology ; Pulmonary Heart Disease ; blood ; physiopathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To examine the effect of genistin on traumatic proliferative vitreoretinopathy (PVR) in rabbits. METHODS: Traumatic PVR was induced in pigmented rabbits by intravitreal injection of platelet rich plasma. The eyes then received an intravitreal injection of dimethyl sulfoxide (0.1 mL), 2 or 40 μg genistin (0.1 mL), and 1 mg fluorouracil(0.1 mL), respectively to form 4 groups. The eyes were examined ophthalmoscopically on distinct days after the surgery and the stage of PVR was evaluated. The model eyes and normal eyes in the 40 μg genistin group carried ERG test on the 28th day. All model eyes in the 4 groups were observed by light microscope on the 28th day. RESULTS: In the control eyes, the retina was detached after 10 d, the PVR had progressed to higher stages with time. In the eyes injected 40 μg genistin or fluorouracil, the PVR also developed; however, the severity of PVR was lower than that in the control eyes. PVR was significantly inhibited in the 40 μg genistin group compared with the control eyes after 14 d (P<0.05). Histological examination of the genistin-treated eyes disclosed no morphological changes, and ERG analysis revealed no significant functional changes. CONCLUSION Intravitreal injection of genistin is safe and effective in reducing traumatic PVR in clinical treatment.
Animals ; Eye Injuries ; complications ; Female ; Intravitreal Injections ; Isoflavones ; administration & dosage ; Male ; Rabbits ; Vitreoretinopathy, Proliferative ; drug therapy ; etiology