Huang-lian-jie-du-decoction modulates glucagon-like peptide-1 secretion in diabetic rats.

Aim Of The Study: Huang-lian-jie-du-decoction (HLJDD), a well-known Chinese herbal formula, has been used for diabetic treatment. The purpose of the study was to investigate whether HLJDD affected glucagon-like peptide (GLP)-1 (7-36) amide level in diabetic rats.

Materials And Methods: Streptozotocin (STZ)-induced diabetic rats were treated with HLJDD at low dose (2 g/kg/day) or high dose (4 g/kg/day).

Organic solvent extraction and metabonomic profiling of the metabolites in erythrocytes.

We used erythrocytes as the model tissue to evaluate an optimal solution for the extraction of intracellular metabolites and time-dependent variation of the metabolome in living cells. Projection to latent structure (PLS) of the GC/MS and LC/MS data suggested that the most efficient solution for the extraction of metabolites from wet erythrocytes (50 mg) could be a methanol-chloroform-water mixture (950 microL, 700:200:50, v/v/v). PLS-discriminant analysis (DA) clearly profiled a time-dependent alternation of metabolic phenotype of erythrocytes.

Validation and application of an LC-ESI-MS method for simultaneous determination of astilbin and its major metabolite 3'-O-methylastilbin in rat plasma.

We herein describe the development of an LC-MS method for simultaneous determination of astilbin and 3'-O-methylastilbin in rat plasma. A simple liquid-liquid extraction procedure was followed by injection of the extracts on to a Shim-pack C(18) column (150 mm x 2.0 mm I.

[Thoughts and experimental exploration on pharmacokinetic study of herbal medicines with multiple-components and targets].

The pharmacokinetic research of traditional Chinese medicines (TMC) is an inalienable part of the chain of TCM modernization and plays an important role in the TCM novel drug development. However, the researching method and system that is consistent with the specific characteristics of TCM, i.e.

HIV protease inhibitor lopinavir-induced TNF-alpha and IL-6 expression is coupled to the unfolded protein response and ERK signaling pathways in macrophages.

HIV protease inhibitor (PI)-associated cardiovascular risk, especially atherosclerosis, has become a major concern in the clinic. Macrophages are key players in the inflammatory response and atherosclerosis formation. We have previously shown that HIV PIs induce endoplasmic reticulum (ER) stress, activate the unfolded protein response (UPR), and increase the synthesis of the inflammatory cytokines, TNF-alpha and IL-6, by regulating the intracellular translocation of RNA binding protein HuR in macrophages.

Cutaneous metabolism in transdermal drug delivery.

The skin is the major interface between the body and the environment. The cutaneous metabolic activity has been identified and widely studied in recent years. It is clear that active enzymes in viable skin tissues have a capacity for bio-transforming topically applied compounds, with a consequence of an altered pharmacological effect.

Subchronic toxicity and plasma pharmacokinetic studies on wogonin, a natural flavonoid, in Beagle dogs.

Aim Of The Study: To investigate subchronic toxicity and pharmacokinetic of wogonin using Beagle dog and to provide foundation for clinical applications of this promising anticancer agent.

Materials And Methods: Wogonin was administered via intravenous infusion at dosages of 60, 30 and 15 mg/kg per day for 90 days followed by subchronic toxicity studies including general body parameters, hematological, plasma biochemical, histopathological, and viscera examinations. Dogs were given single intravenous injection of 20mg/kg wogonin followed by pharmacokinetic parameters estimating.

Pharmacokinetic properties of S-adenosylmethionine after oral and intravenous administration of its tosylate disulfate salt: a multiple-dose, open-label, parallel-group study in healthy Chinese volunteers.

Background: S-adenosylmethionine (SAMe) is an endogenous molecule that plays an important role in cellular metabolism. Despite being widely used as a dietary supplement with claimed benefits for numerous conditions, there is little information about the pharmacokinetic properties of exogenous SAMe.

Objectives: One aim of this study was to characterize the pharmacokinetic properties of SAMe after administration of single and multiple doses of orally and intravenously administered SAMe tosylate disulfate (STD) in healthy male and female Chinese volunteers.

Oxidative demethylenation and subsequent glucuronidation are the major metabolic pathways of berberine in rats.

Present study was designed to explore roles of metabolic clearance in the disposition of berberine (BBR) in rats, with a focus on oxidative metabolism and subsequent glucuronidation. Plasma from rats after intravenous administration of BBR was collected to identify and quantify BBR and its major metabolites. The major circulating metabolites of BBR were oxidative metabolites M1 (via demethylation) and M2 (via demethylenation) and their corresponding glucuronides, with M2-glucuronide approximately 24-fold higher than M1-glucuronide.

A sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of echinacoside and its pharmacokinetic application in rats.

A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of echinacoside in rat plasma was established and fully validated. A single step of liquid-liquid extraction with n-butanol was utilized. Chromatographic separation of the analyte and the internal standard (IS), chlorogenic acid, from the sample matrix was performed using a Capcell-MG C(18) analytical column (100 2.

Characterization of pharmacokinetic profiles and metabolic pathways of 20(S)-ginsenoside Rh1 in vivo and in vitro.

20(S)-Ginsenoside Rh1 is one of the important protopanaxatriol ginsenosides and has been reported to be the main hydrolysis product reaching the systemic circulation after oral ingestion of ginseng. However, its pharmacokinetic characteristics and metabolic fate have never been reported. The present study was therefore designed to elucidate its pharmacokinetic profiles and metabolic pathways both in vivo and in vitro.

Determination of 20(S)-ginsenoside Rh1 and its aglycone 20(S)-protopanaxatriol in rat plasma by sensitive LC-APCI-MS method and its application to pharmacokinetic study.

Liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) method has been developed for the measurement of the concentrations of 20(S)-ginsenoside Rh1 and its aglycone 20(S)-protopanaxatriol in rat plasma with panaxatriol as internal standard. The method involved single liquid-liquid extraction of both 20(S)-ginsenoside Rh1 and 20(S)-protopanaxatriol from plasma samples with n-butanol. The limit of quantification (LOQ) was 5 ng mL(-1) for both compounds.

[Study of pharmacokinetics of aristolochic acid I and II in rats].

Objective: To develop an HPLC method for determination of the plasma concentration of aristolochic acid I (AA I ) and aristolochic acid II (AA II) and study their pharmacokinetics in rats.

Method: The plasma samples were extracted with acetonitrile. The analysis involved a C18 column as stationary phase and methanol, water and acetic acid as mobile phase.

A simple and sensitive HPLC-ESI-MS/MS method for the determination of andrographolide in human plasma.

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the determination of andrographolide in human plasma was established. Dehydroandrographolide was used as the internal standard (I.S.

Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway.

Our previous study showed that insulin restored impaired function and expression of P-glycoprotein in diabetic blood-brain barrier, and further study showed that insulin up-regulated P-glycoprotein expression and function in normal blood-brain barrier, so insulin might be one of the factors that regulated the function and expression of P-glycoprotein in blood-brain barrier of diabetes. In this study, the intracellular pathways that insulin regulated the P-glycoprotein were investigated using primarily cultured rat brain microvessel endothelial cells model. The rat brain microvessel endothelial cells were incubated in normal culture medium containing 50 mU/l insulin and different concentrations of inhibitors for 72 h.

Metabolomic investigation into variation of endogenous metabolites in professional athletes subject to strength-endurance training.

Strength-endurance type of sport can lead to modification of human beings' physiological status. The present study aimed to investigate the alteration of metabolic phenotype or biochemical compositions in professional athletes induced by long-term training by means of a novel systematic tool, metabolomics. Resting venous blood samples of junior and senior male rowers were obtained before and after 1-wk and 2-wk training.

Sensitive determination of 20(S)-protopanaxadiol in rat plasma using HPLC-APCI-MS: application of pharmacokinetic study in rats.

20(S)-Protopanaxadiol (PPD), the main metabolite of protopanoxadiol type ginsenosides (e.g. Rg3 and Rh2), is a very promising anti-cancer drug candidate.

Quantitative determination of ophiopogonin d by liquid chromatography/electrospray ionization mass spectrometry and its pharmacokinetics in rat.

A sensitive and rapid liquid chromatography-mass spectrometric method for the determination of ophiopogonin D in rat plasma was developed and validated. Chromatographic separation was performed on a C (18) column using a step gradient program with the mobile phase of 0.5 mmol/L ammonium chloride solution and acetonitrile.

Toxicological studies of wogonin in experimental animals.

Wogonin, one active ingredient extract from the radix of Scutellaria baicalensis Georgi, is known to possess a broad spectrum of pharmacological, medicinal and therapeutic properties, especially the anticancer activity studied recently. However, no extensive safety studies have been conducted to date. In this paper, the acute and sub-chronic toxicity of the agent were determined using albino mice and Sprague-Dawley rats as animal models.

Berberine promotes glucagon-like peptide-1 (7-36) amide secretion in streptozotocin-induced diabetic rats.

Berberine (BBR), a hypoglycemic agent, has shown beneficial metabolic effects for anti-diabetes, but its precise mechanism was unclear. Glucagon-like peptide-1 (GLP-1) is considered to be an important incretin that can decrease hyperglycemia in the gastrointestinal tract after meals. The aim of this study was to investigate whether BBR exerts its anti-diabetic effects via modulating GCG secretion.

A new method for plasma citrate determination by reversed-phase high-performance liquid chromatography after ultrafiltration extraction: an example for bioequivalence evaluation of a medicinal endogenous substance.

Bioequivalence studies of pharmaceutical preparations of medicinal endogenous substances are generally lacking, as the endogenous background is the main obstacle for both experimental design and drug analysis. We conducted a single-dose, self-control, 3-period crossover study to evaluate the bioequivalence of a sustained-release versus an immediate-release preparation of potassium citrate for the treatment of urinary tract stones. This study included a placebo period to monitor the dynamics of endogenous plasma citrate, which could therefore be subtracted during the data processing.

Diagnostic fragment-ion-based extension strategy for rapid screening and identification of serial components of homologous families contained in traditional Chinese medicine prescription using high-resolution LC-ESI- IT-TOF/MS: Shengmai injection as an example.

The paper presents a modified and universally applicable diagnostic fragment-ion-based extension strategy (DFIBES) to efficiently process the information acquired by liquid chromatography-electrospray ionization source in combination with hybrid ion trap and high-resolution time-of-flight mass spectrometry [LC-(ESI)-IT-TOF/MS], facilitating the structural determination of serial components contained in traditional Chinese medicine prescription (TCMP). The key advantage of DFIBES is that it facilitates the rapid classification of the complicated peaks into well-known chemical families, which significantly simplifies the complicated procedures of structural characterization. Moreover, considering that a certain family of compounds usually produces identical fragment ions, the DFIBES would be widely applicable to many other families of compounds identification besides the presently validated ginsenosides and lignans.

Bioequivalence and pharmacokinetic comparison of a single 200-mg dose of meclofenoxate hydrochloride capsule and tablet formulations in healthy Chinese adult male volunteers: a randomized sequence, open-label, two-period crossover study.

Background: Meclofenoxate hydrochloride is a psychostimulant in the nootropic agent group available in capsule and tablet formulations approved for traumatic cataphora, alcoholic poisoning, anoxia neonatorum, and children's enuresis in China. Although these 2 generic formulations are marketed in China, information regarding their pharmacokinetics and bioequivalence in humans has not been published.

Objective: The aim of this study was to compare the pharmacokinetic properties and bioequivalence of the capsule (test) and tablet (reference) formulations of meclofenoxate hydrochloride 200 mg in healthy Chinese volunteers.

Effects of cyclosporin A and itraconazole on the pharmacokinetics of atorvastatin in rats.

Aim: To evaluate the effects of cyclosporin A and itraconazole, which were used as inhibitors of P-glycoprotein (P-gp) and/or cytochrome P450 (CYP) 3A4 on the pharmacokinetics of atorvastatin in rats.

Methods: The pharmacokinetic parameters of atorvastatin were measured after intravenous (2 mg/kg) and intragastric (10 mg/kg) administration of atorvastatin in rats, which were pretreated with cyclosporin A (5, 10, and 20 mg/kg) or itraconazole (5, 10, and 20 mg/kg).

Results: Compared with the control rats, cyclosporin A and itraconazole altered the pharmacokinetics of atorvastatin significantly.

Global detection and identification of nontarget components from herbal preparations by liquid chromatography hybrid ion trap time-of-flight mass spectrometry and a strategy.

Although the current literature has recorded many reports of identifying components from herbal preparations, all of them were largely limited to target components. This paper provides a novel and generally applicable approach to identifying nontarget components from herbal preparations, based on the use of liquid chromatography ion trap time-of-flight mass spectrometry (LC/MS-IT-TOF). A simple program was originally developed for searching the common diagnostic ions from all experimentally generated ions.