Quality transitivity of Danhong Huayu Koufuye: A study on chemical profiles of medicinal herbs, compound preparation and dosed rat plasma using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Danhong Huayu Koufuye (DHK), an effective Chinese medicine preparation, is mainly used for the treatment of blurred vision and sudden blindness caused by qi stagnation and blood stasis, as well as the absorption period of central retinal vein occlusion. However, the current quality standard is relatively low, only stipulating the content of protocatechualdehyde. Chemical transitivity is the basis for discovering quality markers and is used in quality process control of Chinese medicines.

Effects of total iridoid glycosides of against non-alcoholic steatohepatitis rats induced by high-fat and high-sugar diet through regulation of lipid metabolism.

Objective: To investigate the therapeutic effect of total iridoid glycosides of (TIGP) on non-alcoholic steatohepatitis (NASH).

Methods: SD rats were fed with high-fat and high-sugar diet for 8 weeks to establish NASH. TIGP were given orally at doses of 20, 40 and 80 mg/kg/d for 4 weeks.

Nobiletin potentiates paclitaxel anticancer efficacy in A549/T xenograft model: Pharmacokinetic and pharmacological study.

Background: Nobiletin (N), a polymethoxylated flavone from citrus fruits, enhanced anti-cancer effects of paclitaxel (PTX) in multi-drug resistance (MDR) cancer cells via inhibiting P-glycoprotein (P-gp) in our previous report. But the in vivo chemo-sensitizing effect of nobiletin is unknown. Moreover, considering the nonlinear pharmacokinetics and narrow therapeutic window of PTX, drug-drug interaction should be explored for using nobiletin with PTX together.

Induction of developmental toxicity and cardiotoxicity in zebrafish embryos/larvae by acetyl-11-keto-β-boswellic acid (AKBA) through oxidative stress.

Acetyl-11-keto-β-boswellic acid (AKBA), a triterpenoid from , is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its developmental toxicity and cardiotoxicity.

Direct quantification of intact FIM in monkey plasma using a selective chromatography-tandem mass spectrometry method: Application in a pharmacokinetic study.

FIM protein, which consists of 155 amino acids, was developed as a novel GLP-1 analog to reduce blood glucose, and pharmacodynamic results showed that it had a certain effect when used in treating Alzheimer's disease. The molecular weight of FIM is 16,304 Da. In theory, the concentration of FIM in biological samples should be determined by the ligand binding assay method or indirectly quantified using LC-MS/MS instrumentation.

Paracrine-endocrine FGF chimeras as potent therapeutics for metabolic diseases.

Background: The development of a clinically useful fibroblast growth factor 21 (FGF21) hormone has been impeded by its inherent instability and weak FGF receptor (FGFR) binding affinity. There is an urgent need for innovative approaches to overcome these limitations.

Methods: We devised a structure-based chimerisation strategy in which we substituted the thermally labile and low receptor affinity core of FGF21 with an HS binding deficient endocrinised core derived from a stable and high receptor affinity paracrine FGF1 (FGF1).

Terrestrosin D from attenuates bleomycin-induced inflammation and suppresses fibrotic changes in the lungs of mice.

Terrestrosin D (TED), from L. (Zygophyllaceae), exhibits anti-tumour and anti-inflammatory activities. However, its effects on bleomycin (BLM)-induced pulmonary inflammation and the subsequent fibrotic changes remain unclear.

[Collaborative innovation boosting the safe and rational use of traditional Chinese medicines].

As entering a new era,our country has introduced a series of favorable policies,which may provide the powerful and new momentum for the development of traditional Chinese medicine( TCM). However,more and more attentions have been paid to the safety and effectiveness of TCM. Tripterygium wilfordii Hook.

Diosgenyl Saponin Inducing Endoplasmic Reticulum Stress and Mitochondria-Mediated Apoptotic Pathways in Liver Cancer Cells.

Diosgenin and diosgenyl saponins as the major bioactive compounds isolated from dietary fenugreek seeds, yam roots, etc. possessed strong antitumor effects. To understand their detailed antitumor mechanisms, a fluorophore-appended derivative of diosgenin [Glc/CNHphth-diosgenin (GND)] was synthesized, starting from diosgenin and glucosamine hydrochloride in overall yields of 7-12% over 7-10 steps.

Virtual identification of novel peroxisome proliferator-activated receptor (PPAR) α/δ dual antagonist by 3D-QSAR, molecule docking, and molecule dynamics simulation.

The therapeutic potential of PPARs antagonists extends beyond diabetes. PPARs antagonists represent a new drug class that holds promise as a broadly applicable therapeutic approach for cancer treatment. Thus, there is a strong need to develop a rational design strategy for creating PPARs antagonists.

TEMPO-Catalyzed Direct Conversion of Primary Alcohols to α-Chloroacetals with TCCA Both as an Oxidant and a Chlorination Reagent.

Multistep reactions are often required for the transformation of alcohols to α-chloroacetals via the unstable intermediates aldehydes or α-halo aldehydes. Herein, we report a simplified procedure for practical synthesis of α-chloroacetals using 2,2,6,6-tetramethylpiperidine-1-oxyl as a catalyst and trichloroisocyanuric acid both as an oxidant and a chlorination reagent. The reaction is one-pot, solvent-free and high-yielding.

Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol.

Kaempferol is a natural flavonol that possesses various pharmacological activities, including anti-arthritis effects, yet the underlying mechanisms remain controversial. To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol, collagen-induced arthritis (CIA) mice were treated with kaempferol intragastrically (200 mg · kg · d) and intraperitoneally (20 mg · kg · d). Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index, arthritis index, paw thickness, and inflammatory factors; the bioavailability (1.

Virtual identification of novel PPARα/γ dual agonists by 3D-QSAR, molecule docking and molecular dynamics studies.

Peroxisome proliferator-activated receptors (PPARs) are considered important targets for the treatment of Type 2 diabetes (T2DM). To accelerate the discovery of PPAR α/γ dual agonists, the comparative molecular field analysis (CoMFA) were performed for PPARα and PPARγ, respectively. Based on the molecular alignment, highly predictive CoMFA model for PPARα was obtained with a cross-validated value of 0.

Penetration enhancement of menthol on quercetin through skin: insights from atomistic simulation.

Menthol is an often used skin penetration enhancer because of its high efficiency and relative safety, but the mechanism how it works has not been fully understood up to date. In this study, quercetin was used as a model molecule to investigate the permeability enhancement of menthol through skin lipids. The skin is modeled as a ceramide (CER2) bilayer.

metabolism and pharmacokinetics of bentysrepinine (Y101), an investigational new drug for anti-HBV-infected hepatitis: focus on interspecies comparison.

The objective of this study was to clarify the species differences of pharmacokinetics of Y101 (N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol hydrochloride), a derivative of herbal ingredient with anti-HBV hepatitis activity, in rats, dogs, monkeys and humans.The metabolic stability and metabolite identification studies using liver microsomes , plasma protein binding using a rapid equilibrium dialysis , pharmacokinetic studies were carried out to evaluate the interspecies differences. The toxicokinetic study in monkeys was also investigated.

Discovery of novel and highly selective PI3Kδ inhibitors based on the p110δ crystal structure.

Communicated by Ramaswamy H. Sarma.

Comparative research on the metabolism of metoprolol by four CYP2D6 allelic variants in vitro with LC-MS/MS.

Specific study about the effect of cytochrome P450 2D6 (CYP2D6) polymorphisms on the metabolism of clinic drugs is of great significance for drug safety investigation. Here, the interaction between CYP2D6 variants (*1, *2, *10, *39) and metoprolol (MET) was intensively researched in vitro from the aspect of drug-enzyme kinetic study. To obtain quantitative data, α-hydroxymetoprolol (main metabolite of MET) was selected as an ideal analyte and an LC-MS/MS method was adopted for sample determination.

Identification of absorbed components and their metabolites in rat plasma after oral administration of Shufeng Jiedu capsule using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry.

Rationale: Shufeng Jiedu capsule (SFJDC), a prescription of traditional Chinese medicine, is mainly used for the treatment of acute upper respiratory tract infections. However, the bioactive components remain unclear, which partly limits its quality control and further development. This work aimed to carry out a study of plasma pharmacochemistry to identify the potential bioactive components of SFJDC.

Identification of key transporters mediating uptake of aconitum alkaloids into the liver and kidneys and the potential mechanism of detoxification by active ingredients of liquorice.

Aconite as a commonly used herb has been extensively applied in the treatment of rheumatoid arthritis, as pain relief, as well as for its cardiotonic actions. Aconitum alkaloids have been shown to be the most potent ingredients in aconite, in terms of efficacy against disease, but they are also highly toxic. Apart from neurological and cardiovascular toxicity exposed, the damage to hepatocytes and nephrocytes with long-term use of aconitum alkaloids should also be carefully considered.

Safety, Pharmacokinetics and Pharmacodynamics of TNHH, a Novel Targeted Neutrophil-Inhibitory Hirulog Hybrid Glycoprotein, in Healthy Volunteers.

Background: Targeted neutrophil inhibitory-hirulog (TNHH) is a novel hybrid glycoprotein that may be a potential drug candidate for acute ischaemic stroke.

Objective: The aim of this study was to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of TNHH in healthy volunteers and thereby determine the dose range for future clinical studies.

Methods: This randomized, placebo-controlled study was a single ascending dose design with dose levels of 0.

The Effect of Compound Danshen Dripping Pills on the Dose and Concentration of Warfarin in Patients with Various Genetic Polymorphisms.

Purpose: The combination of warfarin and compound Danshen dripping pill (CDDP) is helpful for patients with both coronary heart disease (CHD) and atrial fibrillation (AF). The main adverse drug reaction of warfarin is bleeding because of its narrow therapeutic index. The safety of a combination therapy with warfarin and CDDP is always a concern.

New Insight into Polydopamine@ZIF-8 Nanohybrids: A Zinc-Releasing Container for Potential Anticancer Activity.

Despite the initial evidence on the role of zinc and zinc transporters in cancer prevention, little attention has been paid to the zinc-derived compounds. In the present work, we reported a strategy to prepare a kind of zinc-releasing container with enhanced biocompatibility and release dynamics using ZIF-8 nanocrystals as the sacrificial templates. Transmission electron microscopy (TEM) analysis demonstrated that the ZIF-8 nanocrystals were gradually etched out in the aqueous media within 48 h, resulting in hollow nanocapsules.

Stereoselective Oxidation Kinetics of Deoxycholate in Recombinant and Microsomal CYP3A Enzymes: Deoxycholate 19-Hydroxylation Is an In Vitro Marker of CYP3A7 Activity.

The primary bile acids (BAs) synthesized from cholesterol in the liver are converted to secondary BAs by gut microbiota. It was recently disclosed that the major secondary BA, deoxycholate (DCA) species, is stereoselectively oxidized to tertiary BAs exclusively by CYP3A enzymes. This work subsequently investigated the in vitro oxidation kinetics of DCA at C-1, C-3, C-4, C-5, C-6, C-6, and C-19 in recombinant CYP3A enzymes and naive enzymes in human liver microsomes (HLMs).

Scutellarin exerts protective effects against atherosclerosis in rats by regulating the Hippo-FOXO3A and PI3K/AKT signaling pathways.

Atherosclerosis (AS), a progressive disorder, is one of the tough challenges in the clinic. Scutellarin, an extract from Herba Erigerontis, is found to have oxygen-free radicals scavenging effects and antioxidant effects. In this study, we aimed to investigate the anti-AS effects of scutellarin is related to controlling the Hippo-FOXO3A and PI3K/AKT signal pathway.

Protective effect of magnolol on oxaliplatin-induced intestinal injury in mice.

Oxaliplatin (OXL) is the first line treatment therapy for gastrointestinal (GI) cancers and often combines with other chemotherapy. However, few reports have studied on its GI toxicity. Magnolol (MG), one of the mainly active constituents in Magnolia, has been reported to treat digestive diseases.