Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.
Administration, Oral ; Alkaloids/analysis* ; Animals ; COVID-19 ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/pharmacokinetics* ; Flavonoids/analysis* ; Mice ; SARS-CoV-2 ; Saponins/analysis* ; Triterpenes/analysis*

The study aimed to establish an UPLC-MS/MS method for the determination of baicalin in rat plasma,in order to study the effect of PEG400 on pharmacokinetics of baicalin and baicalein in normal and gut microbiotadysbiosis rats. Plasma was precipitated with ethyl acetate and determined by UPLC-MS/MS method,with genistein as an internal standard. In terms of specificity,linearity,range,accuracy,precision and stability,the method was suitable for the determination of baicalin in plasma. The gut microbiotadysbiosis rat model was induced through the oral administration with lincomycin hydrochloride(5 g·kg-1·d-1) for one week. Samples of plasma of rats were obtained at different time points,after the rats were administrated with baicalin,baicalin and PEG400. Baicalin in rats were detected by UPLC-MS/MS method,and pharmacokinetic parameters were calculated by DAS 3. 2. 2 software. The results showed that the β-glucosidase activity and the number of colonies in the feces of gut microbiotadysbiosis rats induced by lincomycin hydrochloride were significantly reduced. The Cmaxand AUC0-tof the baicalinand PEG400 group in the intestinal flora were significantly lower than those in the normal rat baicalin and PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the baicalin group and the baicalin+PEG400 group of gut microbiotadysbiosis rats. The Cmaxand AUC0-tof the normal rats baicalin group were significantly higher than those of the gut microbiotadysbiosis rats baicalin group and the baicalin + PEG400 group. There was no significant difference in Cmaxand AUC0-tbetween the normal rat baicalein and PEG400 group and the baicalein group. The Cmaxand AUC0-tof the baicalein group in the gut microbiotadysbiosis rats were lower than those in the normal baicalein group,but significantly higher than those in the baicalein and PEG400 group. PEG400 could increase the absorption of baicalin in normal rats,but is ineffective in gut microbiotadysbiosis rats,with no impact on the absorption of baicalein in rats.
Animals ; Chromatography, Liquid ; Dysbiosis ; drug therapy ; Flavanones ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Gastrointestinal Microbiome ; drug effects ; Polyethylene Glycols ; Rats ; Tandem Mass Spectrometry

The fried method with suet oil,which can strengthen the effect of Epimedium in warming kidney and enhancing Yang,has been widely used in the processing of Epimedium in traditional Chinese medicine. Based on the formation mechanism of Epimedium flavonoids self-assembled micelles in vivo,the synergistic mechanism of processing excipient suet oil was investigated in this paper from the perspective of pharmaceutics. Baohuoside Ⅰ,as representative component of processed Epimedium,was selected as model drug.Average size and zeta potential were measured and the morphology of micelles was observed under transmission electron microscopy. Caco-2 monolayer cell model,rat intestinal perfusion model and in vivo serum drug concentration method were established to investigate the effect of suet oil on the formation and absorption of the baohuosideⅠ bile salt self-assembled micelles. Baohuoside Ⅰ can form selfassembled micelles under the action of sodium deoxycholate. While,adding suet oil into the baohuoside Ⅰ-bile salt micelles( BSDOC) can make it form a more stable system with a smaller average size,higher Zeta potential,lower polydispersity index( PDI) value,significantly improved encapsulation efficiency and drug loading,indicating that suet oil could significantly improve the micelle formation in vivo. In addition,the permeability coefficient of baohuoside Ⅰ in Caco-2 monolayer cells and the four intestinal organs( duodenum,jejunum,ileum and colon) was increased and the oral bioavailability was also improved after adding the suet oil to BS-DOC.All the results demonstrated that the suet oil can promote the formation and absorption of baohuoside Ⅰ self-assembled micelles,so as to enhance its synergistic effects.
Animals ; Caco-2 Cells ; Drugs, Chinese Herbal/pharmacokinetics* ; Epimedium/chemistry* ; Excipients/chemistry* ; Flavonoids/pharmacokinetics* ; Humans ; Intestinal Absorption ; Micelles ; Oils/chemistry* ; Rats

Scutellariae baicalensis is one of the most important traditional Chinese medicinal herbs, mainly distributed in Shandong and Hebei provinces. It has significant pharmacological effects such as antimicrobial activity, anti-inflammatory and antioxidation. Baicalin is one of its main effective components. However, baicalin's low bioavailability has restricted its clinical application. In recent decades, extensive studies have been carried out on the metabolism of baicalin at home and abroad. In order to provide scientific references for baicalin's further studies, this paper would not only review the advances in pharmacokinetics research of baicalin and Chinese herbal preparations containing baicalin, but also make a summary on research status of baicalin.
Drugs, Chinese Herbal ; pharmacokinetics ; Flavonoids ; pharmacokinetics ; Scutellaria baicalensis

OBJECTIVETo study the pharmacokinetics of puerarin (PUE) in Gegen Qinlian Decoction (, GQD), and the effects of PUE dosage variations on the pharmacokinetics of baicalin (BAL) in mice.

METHODSGQD is composed of the concentrated granules of four Chinese herbs. Three dosages with different levels of PUE, including GQD, GQD co-administered with PUE, and GQD co-administration with two times the amount of PUE, were used to research the pharmacokinetics of PUE and BAL in mice. The indirect competitive enzyme-linked immunosorbent assay (icELISA) methods based on an anti PUE-monoclonal antibody (MAb)and BAL-MAb were employed to determine the concentration of PUE and BAL in mice blood.

RESULTSAfter the co-administration of GQD with PUE, the area under the curves (AUC) of PUE increased 2.8 times compared with GQD. At the dose of GQD co-administration at two times that of PUE, the (AUC) of PUE was almost equal to that of GQD co-administration of PUE, showing non-linear pharmacokinetics. The (AUC) of BAL showed a good dose-related increase of PUE (r=0.993) in the range from 100 to 300 mg/kg, indicating that PUE dramatically affects the absorption of BAL in mice. There was no significant difference in the other pharmacokinetic parameters, such as the first time of maximum concentration (T), the second T, or the mean residence time.

CONCLUSIONSThe icELISA methods were successfully applied to pharmacokinetic studies of PUE and BAL in GQD in mice. The dosage variability of PUE of the main ingredient in GQD affects its own pharmacokinetic characteristics and the absorption characteristics of BAL.

Animals ; Drugs, Chinese Herbal ; pharmacokinetics ; Enzyme-Linked Immunosorbent Assay ; Flavonoids ; pharmacokinetics ; Herb-Drug Interactions ; Isoflavones ; pharmacology ; Male ; Mice ; Vasodilator Agents ; pharmacology

Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher C and AUC values (P < 0.05) in type 2 diabetic rats than that in normal rats and the tissue-distribution behaviors of the six flavonoid compounds in hearts, livers, spleens, lungs, kidneys, brains, pancreas, fat and muscle of the type 2 diabetic rats showed obviously differences from the normal rats (P < 0.05). In conclusion, the differences in the pharmacokinetics of oroxyloside and tissue distribution of the six flavanoids in Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.
Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; physiopathology ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Flavonoids ; analysis ; chemistry ; pharmacokinetics ; Male ; Molecular Structure ; Plant Roots ; chemistry ; Rats ; Rats, Wistar ; Reproducibility of Results ; Scutellaria baicalensis ; chemistry ; Tandem Mass Spectrometry ; Tissue Distribution ; physiology

The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection (XXI) in rat plasma, including quercetin 3-O-rutinoside (QCR), kaempferol 3-O-rutinoside (KFR), isorhamnetin 3-O-rutinoside (ISR), bilobalide (BB), and ligustrazine (LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C analytical column (2.1 mm × 100 mm, 3.5 μm) with a mobile phase of 0.1% aqueous formic acid (A)-acetonitrile (B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard (IS). All the calibration curves showed good linearity (r > 0.996) over the concentration range, with the lowest limit of quantification (LLOQ) between 2-18 ng·mL. The intra- and inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries (90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI.
Animals ; Bilobalides ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Disaccharides ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Flavonoids ; blood ; pharmacokinetics ; Glucosides ; blood ; pharmacokinetics ; Kaempferols ; blood ; pharmacokinetics ; Pyrazines ; blood ; pharmacokinetics ; Quercetin ; analogs & derivatives ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

To study the pharmacokinetic effect of different combined administration with monarch drug Ziziphi Spinosae Semen on its main components in rats. Sprague-Dawley (SD) rats were randomly divided into Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi spinosae Semen-Salviae Miltiorrhize Radix et Rhizoma group and Zaoren Ansheng prescription group. After oral administration, HPLC was eluted with the mobile phase of acetonitrle-0.03% phosphate acid water in a gradient mode. The detection wavelength was 280 nm. The pharmacokinetic parameters of spinosin and ferulic acid were calculated by DAS 2. 0 software. Compared with Ziziphi Spinosae Semen group, Ziziphi Spinosae Semen-Fructus Schisandrae Chinensis group, Ziziphi Spinosae Semen-Salviae miltiorrhizae Radix et Rhizoma group showed a lower maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but higher clearance speed (CL/F); whereas the Zaoren Ansheng prescription group showed higher maximum plasma concentration (C(max)) and area under curve (AUC(0-t)) for spinosin and ferulic acid but lower clearance speed (CL/F). Compared with Ziziphi Spinosae Semen group, prescription group showed slower metabolism of spinosin and ferulic
Animals ; Chromatography, High Pressure Liquid ; Coumaric Acids ; administration & dosage ; blood ; pharmacokinetics ; Drug Interactions ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Female ; Flavonoids ; administration & dosage ; blood ; pharmacokinetics ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Ziziphus ; chemistry

The paper aims to study the pharmacokinetic parameters of gastrodin in rats effected by compound compatibilitiy and different doses of Tiangou Jiangya capsule. The extracts from Gastrodiae Rhizoma( equivalent to gastrodin 16.82 mg x kg(-1) and Tiangou jiangya capsule (equivalent to gastrodin 8.410, 16.82, 33.64 mg x kg(-1)) were oral administrated to rats respectively. The plasma were taken at various time points and treated with acetonitrile to measure the contents of gastrodin by HPLC method. The mean plasma concentration-time data were analyzed by 3P97 pharmacokinetic software and the pharmacokinetic parameters between groups were treated by SPSS 16.0. The results showed that gastrodin in rat was fitted to one-compartment model, Cmax and AUC of Tiangou Jiangya capsule were in direct proportion to oral administration, and t1/2Ka had nothing to do with doses, which indicated that gastrodin was fitted first-order rate transfter process in vivo. Morever, comparison with the Gastrodiae Rhizoma extract, isodose gastrodin in Tiangou Jiangya capsule showed a significant decrease for Cmax, Ke and increase for t1/2Ke, V/Fc, this indicated that compound compatibility can delay the absorbtion of gastrodin, prolong the resident time and promote the distribution in vivo, but its bioavailability is not significantly effected.
Administration, Oral ; Animals ; Benzyl Alcohols ; administration & dosage ; chemistry ; pharmacokinetics ; pharmacology ; Blood Pressure ; drug effects ; Female ; Flavonoids ; chemistry ; pharmacology ; Furans ; chemistry ; pharmacology ; Gastrodia ; chemistry ; Glucosides ; administration & dosage ; chemistry ; pharmacokinetics ; pharmacology ; Lignans ; chemistry ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Software

The Qinbai Qingfei concentrated pellets by traditional Chinese medicine theoryand party and group, the rats were given the drugs group, comparison of pharmacokinetics parameters changes of baicalin , discusses the rationality of Qinbai prescription. The rats were gavaged monarch drug group (Huang Qincu extract, mainly forbaicalin), and official medicine group, adjuvant group, medicine group and Qinbai group (Quan Fangzu) the content of baicalin equal as the monarch drug group, in the 28 h collection in rat plasma at different time point, application of HPLC determination of baicalin glycosides in rat plasmaconcentration time curve, with 3P97 practical pharmacokinetics program to process the data Based on the data analysis, baicalin in rat plasma of Qinbai group Cmax is 4 times as big as monarch druggroup, AUC is 6 times as big as monarch drug group; the content of baicalin in plasma of rats the highest is Qinbai group, the minister drug group, adjuvant group, medicine group of baicalin in rat plasma content of less than the Qinbai group, but was significantly higher than that of monarch drug group; the medicine group is slightly higher than that adjuvant the content of baicalin in plasma of rats. The pharmacokinetic results show that the measured plasma concentration in rats that Qinbai can significantly increase Cmax and AUC of baicalin, other components of qinbai can promoted the baicalin absorption in vivo. It showed that the reasonable of Qinbai compound compatibility. The minister drug can promote the absorption of baicalin in vivo.
Animals ; Area Under Curve ; Drugs, Chinese Herbal ; analysis ; pharmacokinetics ; Flavonoids ; blood ; pharmacokinetics ; Intestinal Absorption ; Male ; Rats ; Rats, Wistar