Comparative pharmacokinetics of baicalin in plasma after oral administration of Huang-Lian-Jie-Du-Tang or pure baicalin in MCAO and sham-operated rats

A sensitive and specific HPLC method was developed to analyze baicalin in rat plasma. The author had compared the pharmacokinetics of baicalin after oral administration of HLJDT decoction or pure baicalin in MCAO and sham-operated rats. All the rats were divided into two groups, MCAO and sham-operated rats. Each group contained two subgroups: HLJDT decoction and pure baicalin subgroup. The HLJDT subgroup oral administration of HLJDT decoction extract 10.00 g/kg according to body weight (containing baicalin 400.00 mg/kg according to body weight), the pure baicalin subgroup received a gavages at a dosage of baicalin 400.00 mg/kg according to body weight too. The pharmacokinetics parameters were analyzed by kinetica. The results indicated that the pharmacokinetics of baicalin in rat plasma was non-linear and there were significant differences between different groups. No matter in MCAO or sham-operated rats, pure baicalin had shown better absorption than HLJDT decoction. Whether administration of pure baicalin or HLJDT decoction, the MCAO rats show better, quicker absorption of baicalin than sham-operated rats. It was good for baicalin to exert pharmacological effects on healed cerebrovascular diseases. The method had been applied successfully to pharmacokinetics of baicalin in rat plasma after oral administration of pure baicalin or HLJDT decoction.     

Comparative pharmacokinetic study of paeoniflorin and albiflorin after oral administration of Radix Paeoniae Rubra in normal rats and the acute cholestasis hepatitis rats

A comparative study was designed and conducted to compare the pharmacokinetic difference of paeoniflorin and albiflorin after oral administration of Radix Paeoniae Rubra to normal rats and the acute cholestasis hepatitis rats induced by alpha-naphthylisothiocyanate (ANIT). UPLC-ESI-MS/MS method was employed to determine the level of paeoniflorin and albiflorin in rat plasma using geniposide as the internal standard (IS). Unpaired Student's t-test was used for the statistical comparison. The investigation showed that there were significant differences between the normal rats and the acute cholestasis hepatitis rat groups in calculated parameters, such as AUC(0-t), AUC(0-∞), T(max) and CLz/F. The results indicated that acute liver injury in rats could alter the pharmacokinetics of drug. Since patients are the final users of the drug, it is essential to investigate the pharmacokinetics of the drug in disease status. Therefore, we used normal rats and the acute cholestasis hepatitis rats to study pharmacokinetics of Radix Paeoniae Rubra with the purpose of examining the influence of disease on the metabolic course.     

Puerarin exhibits weak estrogenic activity in female rats

A weak estrogenicity of puerarin on reproductive organs was addressed in female rats. In short-term treatment, immature ovariectomized rats were injected with 0.7 mg/kg BW/day of puerarin, for 14 days. Puerarin did not increase uterus weights, endometrium and myometrium areas, and the percent of cornified cells (%Co), but it increased the number of uterine glands. In long-term treatment, mature rats were injected with 7.0 mg/kg BW/day of puerarin for 140 days. Puerarin did not increase uterus weights, endometrium and myometrium areas, and the number of uterine glands, but a significant increase in the %Co was observed from day 98 onwards.     

Pharmacokinetic study of luteolin,apigenin, chrysoeriol and diosmetin after oral administration of Flos Chrysanthemi extract in rats

Flos Chrysanthemi (the flower of Chrysanthemum morifolium Ramat.) is widely used in China as a food and traditional Chinese medicine for many diseases. Luteolin and apigenin are two main bioactive components in Flos Chrysanthemi, and chrysoeriol and diosmetin are two methylated metabolites of luteolin in vivo by cathechol-O-methyltransferase (COMT). However, there was lack of pharmacokinetic information of chrysoeriol and diosmetin after oral administration of Flos Chrysanthemi extract (FCE). The present study aimed to develop an HPLC-UV method for simultaneous determination of rat plasma concentration of luteolin, apigenin, chrysoeriol and diosmetin and utilize it in pharmacokinetic study of the four compounds after orally giving FCE to rats. The method was successfully validated and applied to the pharmacokinetic study when oral administration of FCE to rats with or without co-giving a COMT inhibitor, entacapone. Chrysoeriol and diosmetin were detected in rat plasma after oral administration of FCE and their concentrations were significantly decreased after co-giving entacapone. Furthermore, AUC of luteolin was significantly increased by entacapone, while that of chrysoeriol was decreased by entacapone, which revealed COMT might play an important role in the disposition of luteolin in rats after dosing of FCE. In conclusion, a sensitive, accurate and reproducible HPLC-UV method for simultaneous determination of luteolin, apigenin, chrysoeriol and diosmetin in rat plasma were developed, pharmacokinetics of chrysoeriol and diosmetin combined with luteolin and apigenin were characterized after oral administration of FCE to rats, which gave us more information on pharmacokinetics and potential pharmacological effects of FCE in vivo.     

Comparative pharmacokinetics of baicalin in normal and the type 2 diabetic rats after oral administration of the Radix scutellariae extract

Radix scutellariae was used alone or in combination with other medicinal herbs in the treatment of type 2 diabetes mellitus in China. At present, the pharmacokinetics of baicalin in type 2 diabetic rats following oral administration of Radix scutellariae extract was investigated. The results showed that the pharmacokinetics (especially AUC) of baicalin in type 2 diabetic rats after oral administration of Radix scutellariae extract was remarkably different from that in normal rats. Then the mechanism which resulted in the increased AUC of baicalin in diabetic rats was investigated from system clearance and presystemic metabolism. And it was found that the increased AUC of baicalin in diabetic rats at least partly resulted from higher production of baicalein in the intestinal tract of type 2 diabetic rats. Moreover, the activity of β-glucuronidase in intestinal mucosa of type 2 diabetic rats was demonstrated to be higher than that in normal rats, which confirmed the results above. In conclusion, the pharmacokinetic behavior of baicalin was significantly altered in type 2 diabetic rats after orally administrated Radix scutellariae extract, which may partly result from the increased activity of intestinal β-glucuronidase under the pathological state of type 2 diabetes mellitus.     

分子印记技术在葛根素分离中的应用及溶剂对聚合物识别能力的影响

通过合成分子印记聚合物以实现葛根素的高效分离。通过静态吸附实验对聚合物的吸附性能进行了评价。使用量子化学的方法对模板分子与功能单体的结合构象进行了计算机模拟,采用UV、IR、1HNMR一系列光谱学分析了分子印记聚合物形成的机理,通过固相萃取考察了聚合物对葛根素的选择性能。该分子印记聚合物对葛根素具有高度选择性,一次性处理葛根素的回收率达到78.0%,纯度可达到86.5%。为从葛根中高效分离富集异黄酮活性成分葛根素提供了一种新方法。     

The studies of anti-inflammatory and analgesic activities and pharmacokinetics of Oxytropis falcate Bunge extraction after transdermal administration in rats

The aim of this study was to evaluate the activities of anti-inflammatory and analgesic of the total flavonoids extraction from Oxytropis falcate Bunge (FEO) after transdermal administration. The pharmacokinetics and absolute bioavailability of FEO in rat, furthermore, was studied. Firstly, the anti-inflammatory and analgesic effects of the FEO were studied by xylene-induced ear edema, adjuvant-induced joint inflammation law in rats, acetic acid-induced writhing and hot-plate tests in mice. Secondly, we developed a sensitive and specific HPLC method to analyze 2′, 4′-dihydroxychalcone (TFC, the mainly ingredient of FEO) in rat plasma to study the pharmacokinetic of TEC. The results showed FEO has anti-inflammatory and analgesic property in a dose-dependent manner, and that the high dose group (90.6 mg/kg) of FEO appeared more significantly effective than the positive drug. From the pharmacokinetic studies of TFC in rats, we got the main pharmacokinetic parameters of TFC, providing a basis for the future studies in clinic.     

Pharmacokinetics of brucine after intravenous and oral administration to rats

The toxicity depending on both dose and administration route is the major obstacle to the development of brucine, a bioactive alkaloid from Semen Strychni. In this study, the apparent partition coefficient and plasma protein binding extent of brucine were determined. In addition, the dose-dependency of the pharmacokinetics of brucine was investigated. Three intravenous (2.5, 5 and 10 mg/kg) and three oral (10, 20 and 40 mg/kg) doses were administered to rats. After intravenous administration, the systemic clearance was reduced and AUC was nonlinearly increased as a function of dose. Upon oral administration, brucine was rapidly absorbed (T_max < 0.5 h), which was consistent with previously reported high Caco-2 P_app values. The increase in AUC was proportional to the increase in dose. The oral bioavailability (F) did not vary with the dose (F = 40.31%, 47.15% and 43.02% for 10, 20, 40 mg/kg doses, respectively). However, the dose-proportionality was not observed with C_max. The values of C_max/Dose were calculated to be 92.92 ± 45.83, 55.73 ± 24.01 and 36.29 ± 22.44 μg/L for 10, 20 and 40 mg/kg, respectively. The results of dose-dependent pharmacokinetic behavior under different administration routes may account for the significantly different toxicities of brucine between intravenous and oral administration.     

棉酚饵剂和莪术醇饵剂对小白鼠抗生育药效试验

在棚舍笼养环境下,使用0.05%棉酚饵剂和0.2%莪术醇饵剂对小白鼠的抗生育效果进行了对比试验研究。结果表明：交配前喂饲0.05%棉酚饵剂和0.2%莪术醇饵剂,与对照组相比较,怀胎下降率、平均胎仔下降率分别为20.0%、9.1%和60.0%、37.5%;交配后喂饲0.05%棉酚饵剂和0.2%莪术醇饵剂,与对照组相比较,怀胎下降率、平均胎仔下降率分别为25.0%、28.1%和33.3%、9.1%;两种抗生育剂对小白鼠均有显著的抗生育作用,但以0.2%莪术醇在交配前喂饲效果最佳;两种抗生育剂对小白鼠无毒性反应。     

葛根提取物的快速提取工艺研究

对葛根的快速提取工艺方法进行了考察,为工业化生产提供可靠的实验数据和理论依据。采用正交实验设计提取方法,HPLC法测定葛根素含量。最佳提取工艺为A2B2C3;影响因素的大小依次为:料液比、脉冲数、电场强度。此法提取葛根中的葛根素达1.91%,得膏率达8.32%。提取工艺可行,经济、省时、回收率高。     

湘葛一号葛根活性物质提取制备葛根功能饮品研究

以葛根为原料,以葛根素为主要评价指标,研究了葛根中各主要活性成分的含量、葛根黄酮的制备、葛根黄酮饮品的稳定性及极端条件的破坏性、葛根黄酮饮品口感及感官指标、葛根黄酮饮品生产工艺等。结果表明:与泰国葛根、粉葛等相比,湘葛一号葛根中葛根素等活性成分含量明显较高。不同浓度乙醇提取葛根总黄酮,以65%乙醇提取效果最好。湘葛一号天然葛根饮品的制备过程中,低浓度(21.6 mg/500 mL)、中浓度(216 mg/500 mL)饮品在不同温度条件下的葛根黄酮均无明显变化,含量稳定;高浓度(360 mg/500 mL)饮品葛根黄酮含量均有不同程度减少,稳定性稍差;中、高浓度饮品葛根黄酮高温易氧化变色,低温易沉淀析出,故低浓度饮品稳定性最佳。在各浓度葛根饮品中,每500 mL含葛根素100 mg及以下的葛根饮品颜色透明清亮;每500 mL含葛根素2.16 mg等低浓度的饮品与纯净水无明显口感差异,21.6 mg级别的饮品口感微苦,并有一种清凉感,适合饮用。     

Pharmacokinetics and tissue distribution study of scoparone in rats by ultraperformance liquid-chromatography with tandem high-definition mass spectrometry

Scoparone is an important constituent of Yinchenhao (Artemisia annua L.), a famous Chinese medicinal plant, and has several known bioactivities, and displayed bright prospects in prevention and therapy of jaundice and liver disorders. The aim of this study was to investigate the in vivo plasma pharmacokinetic and tissue distribution characteristics of scoparone after oral administration. The levels of scoparone in plasma, and tissues were measured by a rapid and sensitive UPLC-MS/MS method. The biosamples were prepared using methanolic precipitation and the separation of scoparone was achieved on a UPLC HSS T3 column by linear gradient elution using water (containing 0.1% formicacid) and acetonitrile (containing 0.1% formic acid) as the mobile phase at a flow rate of 0.5mL/min The total run time was only 3.9min. Our results successfully demonstrate that this method has excellent and satisfactory selectivity, sensitivity, linearity, precision, accuracy and recovery. The estimated pharmacokinetic parameters (i.e., C(max), AUC and CL), were C(max)=14.67mg/L, AUC=81.15mg*h/L, CL=1.23L/h for scoparone. The pharmacokinetic study found that scoparone was distributed and eliminated rapidly in rats. Tissue distribution showed the highest level was observed in liver, followed by the kidney and spleen; the lower level appeared in the muscle, thyroid, and adrenal. It was not detected in the brain which indicated that scoparone does not cross the blood-brain barrier after oral administration. Our developed method was suitable for the study on pharmacokinetics and tissue distribution of scoparone after oral administration.     

Comparative pharmacokinetics of paclitaxel after oral administration of Taxus yunnanensis extract and pure paclitaxel to rats

Taxus yunnanensis (T. yunnanensis) is endemic to China and has been used in traditional medicine for the treatment of cancer, diabetic ailments and others. Paclitaxel is a representative antitumor compound in the Taxus species. The pharmacokinetic behavior of paclitaxel after oral administration of the crude extract of T. yunnanensis has not been investigated. This study attempts to compare the pharmacokinetics of paclitaxel after an oral administration of the crude extract of the twigs and leaves of T. yunnanensis and pure paclitaxel. A UPLC and a UPLC/MS/MS analysis method were developed for the determination of paclitaxel in T. yunnanensis extract and in the comparative pharmacokinetic study. Caco-2 cells were used to investigate the transport profile of paclitaxel in vitro. In the pharmacokinetic study, rats were randomly grouped and administered with T. yunnanensis extract or pure paclitaxel. The results showed that the AUC and C_max of paclitaxel in rats receiving the T. yunnanensis extract were significantly increased than those receiving the pure paclitaxel, and the in vitro Caco-2 cell monolayer transport study found that the coexisting constituents in the extract of T. yunnanensis could inhibit the efflux of paclitaxel. These findings suggested that the oral absorption and bioavailability of paclitaxel in T. yunnanensis extract were remarkably higher when compared with the pure paclitaxel, and the coexisting constituents in the T. yunnanensis extract might play an important role for the enhancement of the oral absorption and bioavailability of paclitaxel.     

An HPLC-ESI-MS method for analysis of loureirin A and B in dragon's blood and application in pharmacokinetics and tissue distribution in rats

A sensitive HPLC-ESI-MS method for the simultaneous determination of loureirin A (LA) and loureirin B (LB) in rat plasma and tissues was developed, and the pharmacokinetic and tissue distribution characteristics of LA and LB were investigated after gavage administration. The samples were pretreated by protein precipitation with ethyl acetate and then separated on a Welch Ultimate XB-C18 column with water-acetonitrile (42:58, v/v) containing 0.1% glacial acetic acid as the mobile phase. The analytes were detected with no interference in multiple reaction monitoring (MRM) mode on an electrospray ionization ion trap mass spectrometer. The analytes showed good linearity over a wide concentration range and the lowest limit of quantification (LLOQ) was 5 ng/mL for LA and 2 ng/mL for LB in matrices. The pharmacokinetic curves of both analytes were best fitted to one-compartment model. It suggested that the analytes absorbed and distributed very quickly in rats. Tissue distribution results showed that the analytes had a wide distribution in tissues and the highest levels for LA and LB were observed in liver followed by kidney, lung, spleen, heart and cerebrum. This work provided the pharmacokinetics and tissue distribution characteristics of LA and LB, which would be instructive for their clinical regiment design.     

Hypoglycemic effect of Mucuna pruriens seed extract on normal and streptozotocin-diabetic rats

The hypoglycemic effect of the aqueous extract of the seeds of Mucuna pruriens was investigated in normal, glucose load conditions and streptozotocin (STZ)-induced diabetic rats. In normal rats, the aqueous extract of the seeds of Mucuna pririens (100 and 200 mg/kg body weight) significantly (P<0.001) reduced the blood glucose levels after an oral glucose load from 127.5+/-3.2 to 75.6+/-4.8 mg% 2 h after oral administration of seed extract. It also significantly lowered the blood glucose in STZ diabetic rats from 240.5+/-7.2 to 90.6+/-5.6 mg% after 21 days of daily oral administration of the extract (P<0.001). Thus, this study shows that M. pruriens has an anti-hyperglycemic action and it could be a source of hypoglycemic compounds.     

Comparative pharmacokinetic and bioavailability studies of three salvianolic acids after the administration of Salviae miltiorrhizae alone or with synthetical borneol in rats

Salviae miltiorrhizae is one of the most commonly used herbal plants in the treatment of numerous ailments including cardiovascular diseases for hundreds of years. According to the theory of traditional Chinese herbal medicine, S. miltiorrhizae is always used in combination with borneol to obtain better pharmacological effects. The purpose of this study was to investigate the effects of borneol on the pharmacokinetic and bioavailability of S. miltiorrhizae. The pharmacokinetics studying on rosmarinic acid, salvianolic acid A and salvianolic acid B which are the main active compounds of S. miltiorrhizae in rat plasma, was achieved using a optimal high-performance liquid chromatographic technique coupled with liquid-liquid extraction method. After administration of either single salvianolic acids or salvianolic acids in combination with borneol, plasma concentrations of rosmarinic acid, salvianolic acid A and salvianolic acid B of male Sprague-Dawley rats were determined at different time points (5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min). In comparison with salvianolic acid extract alone, there were statistically significant differences in pharmacokinetic parameters of rosmarinic acid, salvianolic acid B and salvianolic acid A, and the bioavailability of the three salvianolic acids increased by different degrees when the salvianolic acid extract and borneol were administered together. These results indicated that borneol could enhance the intestinal absorption, decrease the distribution and inhibit the metabolism of salvianolic acids.     

Swietenine: A potential oral hypoglycemic from Swietenia macrophylla seed

Swietenine, a tetranortriterpenoid, was isolated from the Swietenia macrophylla seeds. The in vivo hypoglycemic activity was evaluated against neonatal-streptozotocin induced type 2 diabetic rats. Oral administration of swietenine at 25 and 50 mg/kg body weight per day to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity in type 2 diabetic rats.     

Acute and long-term effects of alkaloid extract of Mitragyna speciosa on food and water intake and body weight in rats

Acute administration of Mitragyna speciosa (MS) extract (45 and 50 mg/kg) significantly resulted in dose-dependent decreases in food and water intakes (P<0.05) in rats. Prolonged suppressing effects were observed following administration of the MS extract (40 mg/kg) for 60 consecutive days. Moreover, the long-term administration also significantly suppressed weight gaining.