Oral Administration In Rats Research Articles

Phytochemical analysis and anti-inflammatory effects of Filipendula vulgaris Moench extracts

Filipendula vulgaris Moench (dropwort) is used in traditional medicine for relieving various inflammation-related diseases. In the present study, the phytochemical profile of F. vulgaris aerial part (FVA) and root (FVR) methanolic extracts was evaluated by LC-DAD-HRMS analysis. Furthermore, their in vitro and in vivo anti-inflammatory effects, as well as their potential cytotoxicity, were assessed. Results showed that the extracts mainly contain phenolics like flavonoids, hydrolyzable tannins, procyanidins, and phenolic acid derivatives, including gaultherin. No in vitro cytotoxicity was found at the highest concentration (50 μg/mL). FVA extract (50 μg/mL) significantly inhibited cyclooxygenase-1 and -2 (COX-1 and COX-2) activities in vitro (>50% inhibition), and FVR extract considerably inhibited COX-2 activity (52.5 ± 2.7%) without affecting COX-2 gene expression in LPS-stimulated THP-1 cells. The extracts demonstrated prominent in vivo anti-inflammatory potential upon oral administration in rats. Especially FVA extract at 100 and 200 mg/kg significantly inhibited carrageenan-induced edema formation. From these results, it can be concluded that F. vulgaris extracts possess interesting anti-inflammatory properties.

The Development of New Factor Xa Inhibitors Based on Amide Synthesis.

Background: Factor Xa (FXa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive tar-gets for oral anticoagulants of new generation.Objective: Our approach for the development of directly acting oral anticoagu-lants (DOAC), FXa inhibitors was demonstrated in this work.Method: Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening meth-ods, where R1, R2 and R3 are some chemical groups and (CONH) are amide bonds connecting R1, R2 and R3. The direction of amide bond (CONH) could be arbitrary for R1, R2 and R2, R3.Results: Chemical modifications were made in the frame of the results, taking into account the structure of FXa, chemical synthesis capabilities, as well as pa-tentability of the target compounds. Subnanomolar potency of several devel-oped compounds was achieved. Several analyzers and various testing-suites have been used to measure the concentration that doubled the prothrombin time (PTx2). Moreover, in human plasma the PTx2 concentration of the compound 217 (DD217) turned out to be 80±20 nM. The compound efficacy has proved by in vivo assays including oral administrations in rats, rabbits and monkeys.Conclusion: The pharmacodynamic profile of DD217 for oral administration in cynomolgus monkeys proves the efficacy of the compound, which makes it promising for the future preclinical trials.

Acute and subchronic toxicities of the ethanol and hot-water extracts from Chinese sumac (Rhus chinensis Mill.) fruits by oral administration in rats

In the present work, acute and subchronic toxicities of the ethanol and hot-water extracts from Rhus chinensis Mill. fruits were performed by oral administration in pathogen-free SD rats. Acute toxicity study was performed at a single dose of 5000 mg/kg for 14 consecutive days. And subchronic toxicity test was conducted by daily oral administration of those two extracts at doses of 312, 625, 1250 and 2500 mg/kg for 30 days. Acute toxicity study showed that the LD50 of the ethanol and hot-water extracts were over 5000 mg /kg. The results of subchronic toxicity showed that no significant adverse effect of those two extracts was observed at 312 and 625 mg/kg. However, the weight gains of rats were significantly inhibited at both 2500 mg/kg groups of the ethanol and hot-water extracts. Moreover, those two extracts exhibited toxicities to heart, liver, spleen and kidney in rats determined by hematological, serum biochemical and/or histological analyses when daily oral administration of 1250 mg/kg and 2500 mg/kg. No significant neurotoxicity was observed in all groups. The results concluded that the low concentration of those two extracts from R. chinensis Mill. fruits can be regarded as safe and used in daily life

Pharmacokinetic properties of a novel inosine analog, 4'-cyano-2'-deoxyinosine, after oral administration in rats.

4′-cyano-2′-deoxyinosine (SK14-061a), a novel nucleoside analog based on inosine, has antiviral activity against the human immunodeficiency virus type 1 that has the ability to acquire resistance against many types of reverse transcriptase inhibitors based on nucleosides. The aim of this study was to investigate the pharmacokinetics studies after its oral administration to rats. For this purpose, we first developed and validated an analytical method for quantitatively determining SK14-061a levels in biological samples by a UPLC system interfaced with a TOF-MS system. A rapid, simple and selective method for the quantification of SK14-061a in biological samples was established using liquid chromatography mass spectrometry (LC-MS) with solid phase extraction. The pharmacokinetic properties of SK14-061a in rats after oral administration were then evaluated using this LC-MS method. SK14-061a was found to be relatively highly bioavailable, is rapidly absorbed from the intestinal tract, and is then mainly distributed to the liver and then ultimately excreted via the urine in an unchanged form. Furthermore, the simultaneous administration of SK14-061a with the nucleoside analog, entecavir, led to a significant alteration in the pharmacokinetics of SK14-061a. These results suggest that the SK14-061a has favorable pharmacokinetic properties with a high bioavailability with the potential for use in oral pharmaceutical formulations, but drug-drug interactions should also be considered.

Determination and pharmacokinetic study of dauricine in rat plasma by UPLC–MS/MS

Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C., a bisbenzylisoquinoline alkaloid derivative, and has shown multiple pharmacological properties. In this work, a sensitive and selective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed for determination of dauricine in rat plasma and its application to pharmacokinetic study of dauricine after intravenous and oral administration in rats. After addition of daurisoline as an internal standard (IS), protein precipitation by acetonitrile was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification. Calibration plots were linear throughout the range 2–600 ng mL−1 for dauricine in rat plasma. Relative standard deviation (RSD) of intra-day and inter-day precision was less than 13%. The accuracy of the method was between 95.8% and 105.9%. Matrix effect of dauricine in rat plasma ranged from 88.0% to 90.3%. Mean recoveries of dauricine in rat plasma ranged from 91.5% to 95.1%. The method was successfully applied to pharmacokinetic study of dauricine after intravenous and oral administration in rats. The bioavailability of dauricine was found to be 55.4% for the first time.

HPLC-MS Determination and Pharmacokinetic Study of 7, 8- Dihydroxyflavone, a Naturally-Occurring Neuroprotective Agent after a Single Oral Administration in Rats

HPLC-MS Determination and Pharmacokinetic Study of 7, 8- Dihydroxyflavone, a Naturally-Occurring Neuroprotective Agent after a Single Oral Administration in Rats

In Vitro and In Vivo Activities of DS-2969b, a Novel GyrB Inhibitor, against Clostridium difficile.

DS-2969b is a novel GyrB inhibitor that is currently under clinical development for the treatment of Clostridium difficile infection (CDI). In this study, the in vitro and in vivo activities of DS-2969b were evaluated. DS-2969b inhibited the supercoiling activity of C. difficile DNA gyrase. DS-2969b showed potent in vitro activity against C. difficile clinical isolates with a MIC90 of 0.06 μg/ml, which was 2-, 32-, and 16-fold lower than the MIC90s of fidaxomicin, vancomycin, and metronidazole, respectively. DS-2969b did not select spontaneously resistant mutants of various C. difficile strains at 4× MIC, and the frequency of resistance development was less than 4.8 × 10-9 In a hamster CDI model, 5-day oral administration of DS-2969b conferred complete protection from recurrence and mortality at 0.3 mg/kg of body weight once a day, in contrast to a 50% survival rate with fidaxomicin at 3 mg/kg once a day and 0% with vancomycin at a 50-mg/kg/dose twice a day. Even a single oral administration of 1 mg/kg of DS-2969b in the CDI model exhibited 100% animal survival without recurrence. DS-2969b was also efficacious by 5-day subcutaneous administration in the CDI model. DS-2969b showed similar levels of fecal excretion after intravenous and oral administrations in rats. These data support further development of DS-2969b as a drug for oral and intravenous treatment of CDI.

YL143, a novel mutant selective irreversible EGFR inhibitor, overcomes EGFRL858R, T790M -mutant resistance in vitro and in vivo.

YL143 was identified as a novel wild‐type sparing EGFRT790M inhibitor with good pharmacokinetic properties. It potently suppresses EGFRL858R/T790M with an 50% inhibitory concentration (IC50) value of 2.0 ± 0.3 nmol/L, but is approximately 92‐folds less potent against EGFRWT kinase. YL143 suppresses cellular proliferation and induces G0/G1 phase arrest and apoptosis in H1975 cells with EGFRL858R/T790M mutation at 30 nmol/L. It also exhibits acceptable pharmacokinetics (PK) parameters with an oral bioavailability value of 25.0% after oral administration in rats and exhibits promising antitumor efficacy in a gefitinib‐resistant human H1975 xenografted model after oral administration of 30 mg/kg/day. These data supported that YL143 could be a promising lead compound for overcoming clinical EGFRT790M resistance of patients with non‐small‐cell lung cancer (NSCLC).

Development of cryptotanshinone-loaded pellets for angina chronotherapy: In vitro/in vivo prediction and evaluation

The clinical manifestations of variant angina is unevenly distributed during the 24 h, thus the in vivo performance of drugs should be tailored according to the angina circadian rhythm. Cryptotanshinone (CTN) is one of the representative bioactive lipid-soluble components of Danshen which has been commonly used for cardiovascular diseases such as angina pectoris. The aim of this study was to develop a novel CTN sustained-released pellets (CTN-SRPs) to precisely synchronize the CTN plasma concentrations with predicted occurrence of angina pectoris for angina chronotherapy. A deconvolution-based method was applied to develop and optimize the CTN-SRPs. The plasma concentration-time curve of CTN immediate-released formulation after oral administration in rats was used as the weight function. The predicted plasma concentration-time curve of CTN-SRPs simulated according to the incidence of variant angina during 24 h was used as the response function. Then the desired drug release profile of CTN-SRPs was calculated based on deconvolution using weight function and response function, and subsequently used for guiding the formulation optimization. CTN-SRPs were prepared with the combinations of PVP, poloxamer 127 and EC as matrix using fluidized bed technology. An orthogonal design was employed to obtain the optimal formulation with its release profile similar with the desired one. Pharmacokinetic studies validated that the actual plasma concentration-time curve of these optimized CTN-SRPs was similar with the predicted one. In addition, the percent errors (%PE) of CTN plasma concentrations in 8–12 h were less than 10%. In conclusion, this deconvolution-based method could be applied to adjust the in vivo performance of drugs for angina chronotherapy.

Experimental study of the anti-tumour activity and pharmacokinetics of arctigenin and its valine ester derivative

Arctigenin (ARG) is a functional active component that has important physiological and pharmacological activities. The anti-tumour and anti-inflammatory activities of ARG show good potential for application and development, but this material has the defect of low water solubility. In this experiment, the valine derivative of ARG (ARG-V) was designed and synthesized to overcome this disadvantage. The ARG amino acid, EDCI and DMAP were raw materials in the addition reaction, with a molar ratio of 1:2:2:0.5. The yield of ARG-V was up to 80%. ARG-V has strong anti-tumour activity in vivo and in vitro. The inhibitory rate of ARG-V was 69.2%, with less damage to the immune organs and different degrees of increased serum cytotoxicity. Moreover, the pharmacokinetics of ARG following oral administration and ARG-V following oral administration in rats were also studied. The Cmax and AUC values of ARG-V showed significant differences compared to ARG. The relative bioavailabilities of three doses of ARG-V compared to ARG were 664.7%, 741.5% and 812.9%. These pharmacokinetic results may be useful for further studies of the bioactive mechanism of ARG and provide a theoretical basic for clinical use.

Pharmacokinetic comparisons of six components from raw and vinegar-processed Daphne genkwa aqueous extracts following oral administration in rats by employing UHPLC–MS/MS approaches

A sensitive UHPLC–MS/MS approach was developed and validated for the quantification of genkwanin, 3′-hydroxygenkwanin, apigenin, luteolin, yuanhuacine and genkwadaphnin in biological samples after oral administration of raw and vinegar-processed Daphne genkwa. Liquiritin and glycyrrhetinic acid were employed as internal standards. Six components were extracted by using protein precipitation with acetonitrile. Chromatographic separation was achieved on a Waters BEH C18 column (50 mm × 2.1 mm, 1.7 μm) by using a mobile phase composed of water (containing 0.1% formic acid) and acetonitrile. Mass spectrometric detection was conducted using multiple reaction monitoring (MRM). The intra- and inter-day precisions of the six analytes were below 4.87%, and the accuracies were within ±5.0%. The extraction recoveries of the six constituents were determined between 97.5% and 105.4% and the matrix effects ranged from 97.3% to 103.7%. All the samples showed satisfactory precision and accuracy after various stability tests. The established approach was successfully applied to the comparative pharmacokinetic study. Compared to the raw group, the parameters of Cmax and AUC0−t of genkwanin, 3′-hydroxygenkwanin, apigenin and luteolin elevated remarkably (p < 0.05) after oral delivery of vinegar-processed Daphne genkwa while the parameters of Cmax and AUC0−t of yuanhuacine and genkwadaphnin decreased significantly (p < 0.05). The results revealed that vinegar-processing could enhance bioavailability of genkwanin, 3′-hydroxygenkwanin, apigenin and luteolin but reduce the bioavailability of yuanhuacine and genkwadaphnin.

Crosslinked poly(vinyl alcohol) hydrogel microspheres containing dispersed fenofibrate nanocrystals as an oral sustained delivery system

Poorly water soluble drugs often show low oral bioavailability due to their low dissolution rate. In the present study, cross-linked poly(vinyl alcohol) hydrogel microspheres were prepared. Nanocrystals of fenofibrate as a model of poorly water soluble drugs were dispersed within the poly(vinyl alcohol) hydrogel microspheres by swelling the microspheres with fenofibrate/methanol solution, followed by evaporation of the solvent methanol. The fenofibrate dissolution rate from the fenofibrate-loaded hydrogel microspheres in a medium simulating gastrointestinal tract conditions was much higher than the dissolution rate of free fenofibrate. And the dissolution assay also showed that fenofibrate released from the hydrogel in a sustained manner. In vivo pharmacokinetic study showed that the fenofibrate-loaded hydrogel microspheres showed much higher bioavailability compared with free fenofibrate, and similar bioavailability but longer half-lives and mean residence time and lower maximum plasma concentration compared with a marked fenofibrate formulation Lipanthyl® after oral administration in rats, indicating that the fenofibrate-loaded PVA hydrogel exhibited lower fluctuation in plasma drug concentration and more sustained release behavior.

Metabolism and pharmacokinetics studies of allyl methyl disulfide in rats

1. Allyl methyl disulfide (AMDS) is one of the main compounds in garlic, whereas its metabolism has not been studied yet.2. In this work, we first identified the metabolites of AMDS in rat erythrocytes and rats using GC–MS. The transformation mechanism study among different metabolites was then conducted. The apparent kinetics of AMDS in rat erythrocytes and pharmacokinetics of AMDS by oral administration in rats were also studied.3. The metabolic pathway study showed that AMDS was mainly metabolized in rats to allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2) through mechanisms of reduction, methylation and oxidation. The transformation mechanism study indicated that AMDS was firstly reduced to allyl mercaptan (AM) in rat erythrocytes, and then methylated to allyl methyl sulfide (AMS) by S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and finally oxidized to AMSO and AMSO2 by liver microsomes. The half-life of AMDS in rat erythrocytes was 6.285 ± 0.014 min while the half-lives of its active metabolites AMSO and AMSO2 in vivo were 18.17 and 17.50 h, respectively. Also, the large AUCs of the two active metabolites were observed, indicating potential applications of AMDS for certain pharmacological effects.

Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model.

Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions.

Pharmacokinetic modeling of single dose Kratom (mitragynine) in rats

Event Abstract Back to Event Pharmacokinetic modeling of single dose Kratom (mitragynine) in rats Yuvenesan Jagabalan1, Hadzliana Zainal1*, Ammar Imad Hazim Al Ganaby2, Vikneswaran Murugaiyah1 and Surash Ramanathan2 1 School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia 2 Center for drug research, University of Science, Malaysia, Malaysia Background Mitragynine the principal alkaloid of M. speciosa leaf has been reported to be responsible for most of its pharmacological effects. Earlier studies have reported the pharmacokinetic properties of mitragynine (MG) following single oral dose administration. However, the selection of MG doses employed in these studies was derived empirically without proper scientific basis. In view of this, the present study was undertaken to determine MG dose-proportionality properties after repeated oral administration in rats. Methods In this study, eighteen rats were randomly assigned into three experimental groups (n = 6, each). The first group rats were orally treated with a single dose of 20 mg/kg MG. The second group was given a single oral dose of 40 mg/kg MG whereas the third group of rats received the 80 mg/kg MG dose orally. Blood was collected from the tail vein before the dosing and thereafter at specific time-points after drug administration. Blood samples were centrifuged and separated plasma samples were frozen prior to analysis using HPLC. Results The pharmacokinetics was best described by two-compartment distribution models with first order absorption. Estimated typical clearance (CL/F) value was 2.21 L.h-1 , absorption rate (Ka) of of 0.82 h-1 and volume of distribution (Vd) of 30.8 L. The stability of the model and predicted performance were confirmed by bootstrap method and numerical predictive check. Conclusion Based on the single dosing experimental rat data, the model provides a useful tool to quantify the pharmacokinetic parameters to propose an optimal dosing regimen in rats. Subsequently, the pharmacokinetic parameter can be modeled to the pharmacodynamics of MG for extrapolation into human use. Keywords: mitragynine, single dosing study, Two-compartment, Pharmacodynamic (PD), pharmacokinetic Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Miscellaneous Citation: Jagabalan Y, Zainal H, Al Ganaby A, Murugaiyah V and Ramanathan S (2019). Pharmacokinetic modeling of single dose Kratom (mitragynine) in rats. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00087 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: PhD. Hadzliana Zainal, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, 11700, Malaysia, hadz@usm.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan Google Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan Google Scholar Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan PubMed Yuvenesan Jagabalan Hadzliana Zainal Ammar Imad Hazim Al Ganaby Vikneswaran Murugaiyah Surash Ramanathan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Glucuronidation is the dominating in-vivo metabolism pathway of herbacetin: Elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats

Glucuronidation is the dominating in-vivo metabolism pathway of herbacetin: Elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats

Toxicological safety evaluation of freeze-dried Protaetia brevitarsis larva powder

White-spotted flower chafer (Protaetia brevitarsis) is an edible insect and its larva was used as a traditional Asian medicine. It's a promising material as a novel food source because of its nutritional components. In this study, as part of the preclinical toxicity program, we evaluated the toxicity of freeze-dried P. brevitarsis larva powder to develop a novel food material. In a single-dose oral toxicity study in rats, there were no changes in mortality, clinical observations, and body weight in rats administered 5000 mg/kg P. brevitarsis larva powder. In a 13-week oral repeated dose toxicity study in rats, there were no adverse effects or changes in mortality, clinical observations, body weight, food consumption, ophthalmology, clinical pathology, necropsy, organ weight, and histopathology at doses of 300, 1000, and 3000 mg/kg/day. In identification of allergic reactions, P. brevitarsis larva powder induced no increases of serum immunoglobulin E and histamine concentrations over 13 weeks of oral administration in rats. In a genotoxicity assessment, P. brevitarsis larva powder didn't provoke bacterial reverse mutations, chromosomal aberrations, and micronucleated reticulocytes. Therefore, freeze-dried P. brevitarsis larva powder shows no evidence of toxic and mutagenic changes under the experimental conditions of the present in vitro and in vivo studies.

Development and Validation of an UPLC-MS/MS Method for Pharmacokinetic Comparison of Five Alkaloids from JinQi Jiangtang Tablets and Its Monarch Drug Coptidis Rhizoma.

JinQi Jiangtang (JQJT) tablets, a Chinese patent medicine approved by the State Food and Drug Administration, are composed of Coptidis Rhizoma, Astragali Radix, and Lonicerae Japonicae Flos, and have a significant effect on diabetes. Coptidis Rhizoma is monarch drug in the prescription. The aim of the present study was to investigate and compare the pharmacokinetics of multiple ingredients from JQJT tablets and Coptidis Rhizoma extract (CRE) following oral administration in rats. Five alkaloids: coptisine chloride, epiberberine chloride, berberine chloride, jatrorrhizine chloride, and palmatine chloride, were simultaneously determined in rat plasma using established and validated ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS). Significant pharmacokinetic differences were observed for the five alkaloids after a single administration of CRE and JQJT tablets. Compared with CRE, the Cmax values of palmatine chloride and jatrorrhizine chloride were decreased significantly, the AUC0–t values of four alkaloids (all except jatrorrhizine chloride) were notably decreased, and the mean residence times of all five alkaloids were significantly decreased after administration of JQJT tablets. The results indicated that the absorption characteristics of the five alkaloids from Coptidis Rhizoma would be influenced by the compatibility of Astragali Radix or Lonicerae Japonicae Flos from JQJT tablets, such that absorption was inhibited and elimination was accelerated. In conclusion, the developed strategy was suitable for the comparison of five alkaloids from JinQi Jiangtang tablets and its monarch drug, which could be valuable for compatibility studies of traditional Chinese medicines.

Glucuronidation is the dominating in vivo metabolism pathway of herbacetin: Elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats

The promising potential benefits of herbacetin in human entail its pharmacokinetic investigations, but the metabolic fate of this natural compound in vivo remains a field of unknown so far. The current study, for the first time, identified and quantified seven herbacetin-metabolites from rat urine, feces and bile after administration of herbacetin to rats. It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin-glucuronides in systemic circulation. The clearance, t1/2 and bioavailability of herbacetin in rats were determined as 16.4 ± 1.92 ml·kg/min, 11.9 ± 2.7 min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed, which was crucial for the further assessments of herbacetin therapeutic effects and mechanism of pharmacological action.

Pre-administration of rats with Helicobacter pylori γ-glutamyl-transpeptidase alleviates osteoarthritis.

To determine the efficacy of Helicobacter pylori γ-glutamyl-transpeptidase (GGT) in osteoarthritis (OA) therapy. Oral administration of rats with rGGT alleviated joint pain in the acute phase of iodoacetate (IA)-induced OA. The CXCL1/IL-6 in blood and in articular tissue as well as circulating granulocytes in the recipients of GGT, were reduced. This might be associated with the expansion of regulatory T cells in the inguinal lymph nodes and increased articular IL-10. We provide preclinical evidence that H. pylori GGT may represent a promising candidate for OA therapy.