Effects of licorice extracts on the pharmacokinetics of brucine in rats and its possible mechanism.

The detoxification effects of licorice are believed to be related to its pharmacokinetic (PK) interference. This paper aimed to evaluate the effects of licorice water extracts (LWE) on the pharmacokinetics of brucine. Rats were administered brucine and/or LWE.

Changes in clinical trials of endocrine disorder and metabolism and nutrition disorder drugs in mainland China over 2010-2019.

With the improvements in relevant policies, laws, and regulations regarding drug clinical trials in China, the quantity and quality of drug clinical trials have gradually improved, and the development prospects of drug clinical trials for endocrine disorders and metabolism and nutrition disorders are promising. Based on information from the clinical trials from the online drug clinical trial registration platform of the National Medical Products Administration, we aimed to review and evaluate the development of clinical trials of drugs for endocrine disorders and metabolism and nutrition disorders in mainland China from 2010 to 2019, as well as the trends over time. A total of 861 trials were carried out on 254 types of drugs for endocrine disorders and metabolism and nutrition disorders, among which 531 (61.

Licorice Extracts Attenuate Nephrotoxicity Induced by Brucine Through Suppression of Mitochondria Apoptotic Pathway and STAT3 Activation.

Licorice, one of the most widely used medicinal herbs in East Asia, has effects such as anti-inflammation, antioxidant, and detoxifying. This study aimed to evaluate the protective effect of licorice on brucine-induced nephrotoxicity. Sprague Dawley rats were administered with brucine intraperitoneally for 7 consecutive days with or without treatment with licorice.

Quantitative monitoring of a panel of stress-induced biomarkers in human plasma by liquid chromatography-tandem mass spectrometry: an application in a comparative study between depressive patients and healthy subjects.

Using a metabolomic approach, we have found that stress can induce oxidative damage by disturbing the creatine/phosphocreatine shuttle system and purinergic pathway, leading to an excessive membrane breakdown. To further validate our findings and to monitor the biological impact of stress in research of clinical psychiatry, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously determine a panel of biomarkers comprising choline, creatine, purinergic metabolites, neurosteroids, lysophosphatidylcholines, and phosphatidylethanolamines in human plasma. After optimization of the extraction protocol, all the 15 analytes plus 4 internal standards with distinct polarities were extracted into an organic phase using methyl tert-butyl ether/methanol (1:1, v/v).

Topical treatments for diabetic neuropathic pain.

Diabetic neuropathic pain (DNP) has a huge impact on quality of life and can be difficult to treat. Oral treatment is the most frequently used method for DNP, but its use is often limited by systemic side effects. Topical use of drugs as an alternative option for DNP treatment is currently gaining interest.

European versus Asian differences for the associations between paraoxonase-1 genetic polymorphisms and susceptibility to type 2 diabetes mellitus.

Many studies have examined the associations between paraoxonase-1 (PON1) genetic polymorphisms (Q192R, rs662 and L55M, rs854560) and the susceptibility to type 2 diabetes mellitus (T2DM) across different ethnic populations. However, the evidence for the associations remains inconclusive. In this study, we performed a meta-analysis to clarify the association of the two PON1 variants with T2DM risk.

The Associations between Apolipoprotein E Gene Epsilon2/Epsilon3/Epsilon4 Polymorphisms and the Risk of Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus.

Apolipoprotein E (APOE) plays important roles in lipoprotein metabolism and cardiovascular disease. Evidence suggests the gene epsilon2/epsilon3/epsilon4 (ε2/ε3/ε4) polymorphisms might be associated with the susceptibility of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, no clear consensus has yet been established.

The Ethanol Extract of Licorice Protects against Triptolide-Induced Oxidative Stress through Activation of Nrf2.

To investigate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2) in licorice ethanol extract (LEE) against triptolide- (TP-) induced hepatotoxicity, HepG2 cells were exposed to LEE (30, 60, and 90 mg·L) for 12 h and then treated with TP (50 nM) for 24 h. Besides, an acute liver injury model was established in ICR mice by a single dose of TP (1.0 mg·kg, i.

Danshen modulates Nrf2-mediated signaling pathway in cisplatin-induced renal injury.

Danshen, an efficacious agent for cardiovascular diseases, has been found to play an essential role in kidney injury. In the present study, the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model. Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment.

Pharmacokinetics and relative bioavailability of a generic amisulpride tablet in healthy Chinese volunteers
.

Objective: To assess and compare the pharmacokinetic properties and bioavailability of a newly developed formulation of amisulpride with those of a conventional formulation in healthy Chinese volunteers under fasting state.

Materials And Methods: A single-dose, two-sequence crossover study was designed. 20 healthy subjects (14 males and 6 females) were randomized into two groups.

Impact of CYP2C19 Genotype and Liver Function on Voriconazole Pharmacokinetics in Renal Transplant Recipients.

Background: Invasive fungal infection (IFI) is one of the leading causes of early death after renal transplantation. Voriconazole (VRC) is the first-line drug of IFI. Because of the large inter- and intraindividual variability in VRC plasma concentrations and the narrow therapeutic window for treating patients with IFIs, it is crucial to study the factors which could influence pharmacokinetic variability.

An LC-MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study.

Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Liquorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid chromatography-mass spectrometric method (LC-MS) was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma.

Quantitative analysis of valsartan by two-dimensional liquid chromatography (2D-HPLC) and its application in a bioequivalence study in Chinese volunteers
.

Purpose: To develop a sensitive, two-dimensional liquid chromatography (2D-LC) method for determination of valsartan, applied to investigate bioequivalence of two valsartan tablets in Chinese volunteers under fasting condition.

Methods: A full automatic 2D-HPLC system was used to quantify valsartan in human plasma. The analytes were extracted by protein precipitation, using telmisartan as internal standard.

A sensitive LC-MS/MS method for analysis of pericyazine in presence of 7-hydroxypericyazine and pericyazine sulphoxide in human plasma and its application to a comparative bioequivalence study in Chinese healthy volunteers.

A robust and highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of pericyazine in human plasma. The plasma sample was alkalized with sodium hydroxide solution and handled by liquid-liquid extraction with ethyl acetate after adding perphenazine as an internal standard (IS). The analytes were separated on an Ultimate™ AQ-C18 analytical column at 40°C, with a gradient elution consisting of A (aqueous phase: 5mM ammonium acetate buffer solution containing 0.

Isoliquiritigenin protects against triptolide-induced hepatotoxicity in mice through Nrf2 activation.

Isoliquiritigenin, a flavonoid found in licorice, has been considered as an antioxidive and hepato-protective agent. Recent studies have shown that a possible mechanism for triptolide-induced hepatotoxicity is related to oxidative damage induced by reactive oxygen species. This study was done to investigate the protection effect of isoliquiritigenin against triptolide-induced hepatotoxicity and the mechanism involved.

The Protective Effects of Isoliquiritigenin and Glycyrrhetinic Acid against Triptolide-Induced Oxidative Stress in HepG2 Cells Involve Nrf2 Activation.

Triptolide (TP), an active ingredient of Tripterygium wilfordii Hook f., possesses a wide range of biological activities. Oxidative stress likely plays a role in TP-induced hepatotoxicity.

Progress on mechanism of Tripterygium wilfordii-induced liver injury and detoxification mechanism of licorice.

Tripterygium wilfordii has exihibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anti-tumor and anti-fertility. T. wilfordii have been used for the therapy of inflammation and autoimmune diseases including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus clinically.

A protective mechanism of licorice (Glycyrrhiza uralensis): isoliquiritigenin stimulates detoxification system via Nrf2 activation.

Ethnopharmacological Relevance: Licorice (Glycyrrhizae radix), the root of Glycyrrhiza uralensis Fisch. (Leguminosae), is mainly used to moderate the characteristics of toxic herbs in Traditional Chinese Medicine, which could be partly interpreted as detoxification. However, the underlying mechanism is still not fully elucidated.

Quantitative analysis of trazodone in human plasma by using HPLC-fluorescence detector coupled with strong cation exchange chromatographic column: application to a pharmacokinetic study in Chinese healthy volunteers.

A simple, selective, and sensitive high performance liquid chromatography (HPLC) procedure has been developed for determination of trazodone in human plasma. Prazosin was employed as the internal standard (IS). Sample preparation involved liquid-liquid extraction by methyl tert-butyl ether after alkalinization with ammonia.

Validated UPLC-MS/MS method for determination of moclobemide in human brain cell supernatant and its application to bidirectional transport study.

A simple and sensitive analytical method based on ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for determination of moclobemide in human brain cell monolayer as an in vitro model of blood-brain barrier. Brucine was employed as the internal standard. Moclobemide and internal standard were extracted from cell supernatant by ethyl acetate after alkalinizing with sodium hydroxide.

Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics of the P-glycoprotein substrate talinolol in healthy volunteers.

Purpose: To investigate the effects of repeated glycyrrhizin ingestion on the oral pharmacokinetics of talinolol, a probe drug for P-glycoprotein (P-gp) activity in humans.

Methods: Fourteen healthy adult male subjects were enrolled in a two-phase randomized crossover-design study. In each phase the volunteers received placebo or compound glycyrrhizin tablets (75 mg glycyrrhizin three times daily) for 6 days.

Metabolomic analysis of biochemical changes in the plasma and urine of first-episode neuroleptic-naïve schizophrenia patients after treatment with risperidone.

Early findings propose that impaired neurotransmission in the brain plays a key role in the pathophysiology of schizophrenia. Recent advances in understanding its multiple etiologies and pathogenetic mechanisms provide more speculative hypotheses focused on even broader somatic systems. Using a targeted tandem mass spectrometry (MS/MS)-based metabolomic platform, we compared metabolic signatures consisting of monoamine and amino acid neurotransmitter (NT) metabolites in plasma/urine simultaneously between first-episode neuroleptic-naïve schizophrenia patients (FENNS) and healthy controls before and after a 6-week risperidone monotherapy, which suggest that the patient NT profiles are restoring during treatment.

Influence of P-glycoprotein on brucine transport at the in vitro blood-brain barrier.

Brucine is a central agonist that can pass through the blood-brain barrier (BBB). The goal of this study is to examine whether brucine is one of the substrates of the drug transporter P-glycoprotein (P-gp) and to examine the effects of P-gp on the brucine transport at the in vitro BBB model. The P-gp ATPase assay was utilized to investigate the in vitro affinity of P-gp to brucine.

Development and validation of a sensitive U-HPLC-MS/MS method with electrospray ionization for quantitation of ranolazine in human plasma: application to a clinical pharmacokinetic study.

A simple, sensitive and high-throughput ultra high-performance liquid chromatography electrospray ionization mass spectrometry (U-HPLC-ESI-MS/MS) method has been developed and validated for the determination of ranolazine in human plasma. Propafenone was employed as the internal standard (I.S.

Abnormal plasma monoamine metabolism in schizophrenia and its correlation with clinical responses to risperidone treatment.

Abnormalities in plasma monoamine metabolism reflect partly the illness of schizophrenia and sometimes the symptoms. Such studies have been repeatedly reported but have rarely taken both metabolites and parent amines or inter-amine activity ratios into account. In this study, the monoamines, their metabolites, turnovers and between-metabolite ratios in plasma were measured longitudinally in 32 schizophrenic patients treated with risperidone for 6 weeks, to examine possible biochemical alterations in schizophrenia, and to examine the association between treatment responses and psychopathology assessed according to the Positive and Negative Syndrome Scale (PANSS).