Subacute Assessment of the Toxicity and Antidepressant-Like Effects of Origanum Majorana L. Polyphenols in Swiss Albino Mice

Origanum majorana L. is a plant commonly used in folk medicine to treat depression and several neurological disorders. This study aims to evaluate the antidepressant-like effect of the Origanum majorana L. polyphenols (OMP) obtained from the aerial parts using two different depression model tests: The forced swimming test (FST) and the tail suspension test (TST) in Swiss albino mice. The experiments were performed on days 1, 7, 14, and 21 with daily administration of different treatments. Two different doses were chosen for this study (50 and 100 mg/kg), and paroxetine was used as a positive control. Immobility as a consequence of the depression state was significantly reduced following the treatment with OMP, indicating an antidepressant effect. A subacute toxicity study was also performed following the Organization for Economic Co-operation and Development (OECD) Guidelines (407), showing no sign of toxicity for the studied doses. The phytochemical screening revealed the presence of 12 components, all belonging to polyphenols: Arbutin, rosmarinic acid, ursolic acid, quercetin-3-O-glucoside, quercetin-7-O-glucuronic acid, luteolin-7-O-glucoside, kaempferol-3-0-glucuronic acid, Kaempferol-3-0-pentose, caffeic acid, catechin, quercetin, and rutin. These findings suggest that O. majorana has interesting antidepressant-like properties, which deserve further investigation.     

Contemporary concepts in toxicology: a novel multi-instructor general education course to enhance green chemistry and biomedical curricula

ABSTRACT

An undergraduate course in contemporary toxicology was developed by the Chemistry Department at Grand Valley State University (GVSU) with assistance and participation from the Dow Chemical Company Toxicology and Environment Research and Consulting department (DOW-TERC). It was designed as an overview of xenobiotic effects on human health and environment and focuses on new predictive approaches used early in sustainable product development. Planned as a hybrid, administrated by GVSU, with lectures by both GVSU and DOW-TERC scientists, the course included classical elements of dose/response, absorption, distribution, metabolism, excretion, and newer advances in predictive toxicology, bioprofiling, databases, and product stewardship. Student performance assessments on a series of scaffolded case study, journaling, and exams, indicated their emerging ability to think critically and to apply their growing toxicology knowledge in solving problems. Opinion surveys indicate students’ positive responsiveness to the multi-instructor format. This course can serve as a model for programs at other institutions.     

Imaging cytoplasmic cAMP in mouse brainstem neurons

Background  

cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca²⁺ levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.     

Perturbed Evolution Problems with Continuous Bounded Variation in Time and Applications

This paper is devoted to the study of evolution problems of the form \(-\frac {du}{dr}(t) \in A(t)u(t) + f(t, u(t))\) in a new setting, where, for each t, A(t) : D(A(t)) → 2 ^H is a maximal monotone operator in a Hilbert space H and the mapping t?A(t) has continuous bounded or Lipschitz variation on [0, T], in the sense of Vladimirov’s pseudo-distance. The measure dr gives an upper bound of that variation. The perturbation f is separately integrable on [0, T] and separately Lipschitz on H. Several versions and new applications are presented.     

Analytical and semipreparative enantioseparation of 9-hydroxyrisperidone, the main metabolite of risperidone, using high-performance liquid chromatography and capillary electrophoresis. Validation and determination of enantiomeric purity

The HPLC semipreparative enantioseparation of 9-hydroxyrisperidone (9-OHRisp) was studied by optimizing various experimental conditions: the nature of the chiral stationary phase (CSP), mobile phase composition, temperature and analyte loading. This semipreparative enantioseparation was successfully completed using the polysaccharide Chiralcel OJ chiral stationary phase and a n-hexane/ethanol/methanol (50/35/15, v/v/v) ternary mobile phase. To assess the enantiomeric purity of both isolated isomers, three analytical methods using UV detection were developed and validated: one CE method using dual cyclodextrin mode and two HPLC methods using either the Chiralcel OJ CSP in normal-phase mode or the alpha-acid glycoprotein (alpha-AGP) CSP in reversed-phase mode. The three methods make it possible to obtain excellent enantioseparations (R(s) >3) with analysis times lower than 15 min, and the calculated limits of detection allow for the determination of minor enantiomeric impurities (0.1%). Enantiomeric purity obtained for dextrorotatory and levorotatory enantiomers was superior to 99.9% and equal to 98.9%, respectively, which proved the success of the semipreparative enantioseparation. A brief comparison of the performances of the analytical methods completes this work.     

Enantioselective analysis of the antipsychotic 9-hydroxyrisperidone, main metabolite of risperidone, by chiral capillary EKC using dual CDs

An analytical method for the enantioseparation of the 9-hydroxyrisperidone, main metabolite of the antipsychotic risperidone (Risp), was developed by CD-EKC in the dual CDs mode using anionic and neutral CDs at acidic pH 2.5. Preliminary experiments allowed us to select the more suitable couple of CDs composed of sulfated-alpha-CD and hydroxypropylated-beta-CD. The optimization of the main experimental parameters (concentrations of both CDs and concentration of the phosphate buffer) was based on a central composite design through the response surface methodology. Then, the influence of the voltage and the temperature on the enantioseparation was studied using the classical univariate approach. The final method permits to resolve the enantiomers of the 9-hydroxyrisperidone with a resolution of 3.13 and an analysis time of about 13 min. Finally, this method was successfully applied for the simultaneous determination of Risp and the enantiomers of 9-hydroxyrisperidone (9-OHRisp).     

Cysteine as a Multifaceted Player in Kidney,the Cysteine-Related Thiolome and Its Implications for Precision Medicine

In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.