New horizons for the role of selenium on cognitive function: advances and challenges.

Cognitive deficits associated with oxidative stress and the dysfunction of the central nervous system are present in some neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Selenium (Se), an essential microelement, exhibits cognition-associated functions through selenoproteins mainly owing to its antioxidant property. Due to the disproportionate distribution of Se in the soil, the amount of Se varies greatly in various foods, resulting in a large proportion of people with Se deficiency worldwide. Numerous cell and animal experiments demonstrate Se deficiency-induced cognitive deficits and Se supplementation-improved cognitive performances. However, human studies yield inconsistent results and the mechanism of Se in cognition still remains elusive, which hinder the further exploration of Se in human cognition. To address the urgent issue, the review summarizes Se-contained foods (plant-based foods, animal-based foods, and Se supplements), brain selenoproteins, mechanisms of Se in cognition (improvement of synaptic plasticity, regulation of Zn2+ level, inhibition of ferroptosis, modulation of autophagy and de novo synthesis of L-serine), and effects of Se on cognitive deficits, as well as consequently sheds light on great potentials of Se in the prevention and treatment of cognitive deficits.

Breast milk selenocystine as a biomarker for selenium intake in lactating women at differential geographical deficiency risk in China.

BACKGROUND AND OBJECTIVES: A reliable biomarker for optimal selenium (Se) intake in lactating women is not currently available. METHODS AND STUDY DESIGN: Daily dietary Se intake in lactating women was calculated from a 24-hour meal record survey for over 3 days. Se levels in plasma and breast milk were measured through inductively coupled plasma mass spectrometry. Plasma selenoprotein P 1 levels and glutathione peroxidase 3 activity were measured using an enzyme-linked immunosorbent assay. Ultra-performance liquid chromatography-tandem mass spectrometry was used to analyze proteinaceous Se species in enzymatically digested breast milk. RESULTS: Dietary Se intakes of lactating women from Liangshan, Beijing, and Enshi were 41.6±21.2 ng/d, 51.1±22.6 ng/d, and 615±178 ng/d, respectively (p<0.05). The Se levels in the blood and breast milk were significantly associated with the dietary Se intake (p<0.05). The proteinaceous Se species in breast milk were SeMet and SeCys2. The levels of SeMet in the lactating women from Liangshan, Beijing, and Enshi were 3.31±2.44 ng Se/mL, 7.34±3.70 ng Se/mL, and 8.99±9.64 ng Se/mL, while that of SeCys2 were 13.7±12.0 ng Se/mL, 35.6±20.9 ng Se/mL, and 57.4±13.2 ng Se/mL, respectively. Notably, the concentration of SeCys2, the metabolite of unstable SeCys, reached a saturation platform, whereas no similar phenomenon were found for the total Se SeMet from Secontaining proteins. CONCLUSIONS: SeCys2 in breast milk is a potential biomarker for determining the optimal Se intake in lactating women.

Quantitative and Discriminative Evaluation of Contents of Phenolic and Flavonoid and Antioxidant Competence for Chinese Honeys from Different Botanical Origins.

Phenolics and flavonoids in honey are considered as the main phytonutrients which not only act as natural antioxidants, but can also be used as floral markers for honey identification. In this study, the chemical profiles of phenolics and flavonoids, antioxidant competences including total phenolic content, DPPH and ABTS assays and discrimination using chemometric analysis of various Chinese monofloral honeys from six botanical origins (acacia, Vitex, linden, rapeseed, Astragalus and Codonopsis) were examined. A reproducible and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was optimized and validated for the simultaneous determination of 38 phenolics, flavonoids and abscisic acid in honey. Formononetin, ononin, calycosin and calycosin-7-O-ß-d-glucoside were identified and quantified in honeys for the first time. Principal component analysis (PCA) showed obvious differences among the honey samples in three-dimensional space accounting for 72.63% of the total variance. Hierarchical cluster analysis (HCA) also revealed that the botanical origins of honey samples correlated with their phenolic and flavonoid contents. Partial least squares-discriminant analysis (PLS-DA) classification was performed to derive a model with high prediction ability. Orthogonal partial least squares-discriminant analysis (OPLS-DA) model was employed to identify markers specific to a particular honey type. The results indicated that Chinese honeys contained various and discriminative phenolics and flavonoids, as well as antioxidant competence from different botanical origins, which was an alternative approach to honey identification and nutritional evaluation.

Ultra-high-performance liquid chromatography-tandem mass spectrometry for pharmacokinetics of bakuchiol in rats.

Psoralea Corylifolia L. is a traditional Chinese medicine with many beneficial effects in medical therapies. Bakuchiol was the main active ingredient of Psoralea Corylifolia L., used for the treatment of various diseases and also as a natural food additive. A specific and reliable ultra-high performance liquid chromatography-tandem mass spectrometry has been developed and fully validated for the quantification of bakuchiol in rat plasma. Chromatographic separation of bakuchiol and an internal standard, daidzein, was achieved on a Hypersil Gold C18 column with gradient elution that consisted of methanol and water at a flow rate of 0.2 mL/min. The compounds were detected at negative ionization mode using mass transition m/z 255.2 → 172.0 and 252.9 → 132.0 for bakuchiol and daidzein, respectively. Good linearity was obtained over the range of 2-1000 ng/mL and the lower limit of quantification was 2 ng/mL. The intra- and inter-day accuracies ranged from 91.1 to 105.7% and precisions (relative standard deviations) were within 9.3%. Bakuchiol was found to be stable under three freeze-thaw cycles, short-term temperature, post-preparative and long-term temperature conditions. The method was applied to a pharmacokinetic study of bakuchiol intravenously administered to rats at a dose of 5 mg/kg.

Identification of Factors on Blood Selenium Levels in the US Adults: A Cross-Sectional Study.

Selenium (Se) is an essential trace element for humans and its low or high concentration in vivo is associated with the high risk of many diseases. It is important to identify influential factors of Se status. The present study aimed to explore the association between several factors (Se intake, gender, age, race, education, body mass index (BMI), income, smoking and alcohol status) and blood Se concentration using the National Health and Nutrition Examination Survey 2017-2020 data. Demographic characteristics, physical examination, health interviews and diets were compared among quartiles of blood Se concentration using the Rao-Scott χ2 test. Se levels were compared between the different groups of factors studied, measuring the strength of their association. A total of 6205 participants were finally included. The normal reference ranges of blood Se concentration were 142.3 (2.5th percentile) and 240.8 µg/L (97.5th percentile), respectively. The mean values of dietary Se intake, total Se intake and blood Se concentration of the participants were 111.5 µg/day, 122.7 µg/day and 188.7 µg/L, respectively, indicating they were in the normal range. Total Se intake was the most important contributor of blood Se concentration. Gender, race, education status, income, BMI, smoking and alcohol status were associated with blood Se concentration.

Pharmacokinetics of chromium-enriched yeast in rats following oral administration.

Chromium (Cr) is required for carbohydrate, lipid, and protein metabolisms in humans and animals. Cr insufficiency is associated with diabetes and cardiovascular disease. Chromium-enriched yeast (CrY) is a widely used Cr dietary supplement, but its pharmacokinetics remains unavailable. CrY was orally administered to rats at a single dose of 1 mg Cr/kg, and plasma Cr concentration at different time points was measured by inductively coupled plasma mass spectrometry. Pharmacokinetics of CrY in rats was well fitted to a non-compartmental model. Plasma Cr concentration reached the maximum of 8.68 ± 2.87 ng/mL at 0.25 h, and gradually decreased to 4.05 ± 0.47 ng/mL at 24 h. CrY was rapidly absorbed into the blood and was slowly eliminated after the oral administration, which could lead to the accumulation of Cr in vivo.

Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects.

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis.

Advances in Pharmacokinetic Mechanisms of Transporter-Mediated Herb-Drug Interactions.

As the use of herbs has become more popular worldwide, there are increasing reports of herb-drug interactions (HDIs) following the combination of herbs and drugs. The active components of herbs are complex and have a variety of pharmacological activities, which inevitably affect changes in the pharmacokinetics of chemical drugs in vivo. The absorption, distribution, metabolism, and excretion of drugs in vivo are closely related to the expression of drug transporters. When the active components of herbs inhibit or induce the expression of transporters, this can cause changes in substrate pharmacokinetics, resulting in changes in the efficacy and toxicity of drugs. In this article, the tissue distribution and physiological functions of drug transporters are summarized through literature retrieval, and the effects of herbs on drug transporters and the possible mechanism of HDIs are analyzed and discussed in order to provide ideas and a reference for further guiding of safe clinical drug use.

Speciation Analysis of Chromium in Chromium-Enriched Yeast by Ion Chromatography-Inductively Coupled Plasma Mass Spectrometry.

Chromium-enriched yeast (CrY) is a popular Cr dietary supplement, but suitable speciation analysis of highly toxic Cr(VI) in CrY is not available. Ion chromatography-inductively coupled plasma mass spectrometry method was firstly developed and validated for the quantification of Cr(III) and Cr(VI). Ultrasound-assisted weakly alkaline EDTA solution combined with boiling was used to extract two Cr species in CrY. Two species were separated on two successive anion-exchange columns using a mobile phase of 0.6 mmol/L EDTA and 76 mmol/L NH4NO3 solution. The method was sensitive, accurate (92.4-100.9%), and precise (0.8-3.1%). Species of Cr(VI) were not found in CrY.

Comparison of Bioavailability, Pharmacokinetics, and Biotransformation of Selenium-Enriched Yeast and Sodium Selenite in Rats Using Plasma Selenium and Selenomethionine.

For the first time, bioavailability, pharmacokinetics, and biotransformation of selenium-enriched yeast (SeY) and sodium selenite (Na2SeO3) in rats were systemically compared by analyzing free selenomethionine (SeMet), total SeMet, and selenium (Se). After SeY and Na2SeO3 were orally administered to rats at a dose of 100 µg Se/kg, plasma free SeMet, total SeMet, and Se at various time points were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Based on Se and total SeMet, the relative bioavailability values of SeY compared with Na2SeO3 were 144% and 272%, respectively. For the rats treated with SeY, 0.73-2.68% of total Se was biotransformed to free SeMet, 14.3-20.4% to SeMet-proteins and albumin-bound SeMet, and 75.9-82.3% to selenoproteins in plasma. SeY had higher bioavailability than Na2SeO3 based on Se and total SeMet levels. Plasma SeMet was the optimal biomarker of SeY status in vivo.

In vitro erythrocytic uptake studies of artemisinin and selected derivatives using LC-MS and 2D-QSAR analysis of uptake in parasitized erythrocytes.

The purpose of the present investigation was to characterize the partitioning of artemisinin and its derivatives into both non-parasitized as well as Plasmodium falciparum parasitized red blood cells (RBCs). Artemisinin and selected derivatives at concentrations of 3.55microM were incubated in RBCs with a hematocrit of 33% for 2h at 37 degrees C, extracted from RBCs by solid phase extraction, and analyzed using liquid chromatography-mass spectrometry in positive electro-spray ionization mode with methanol as mobile phase. The uptake percent of artemisinin and selected derivatives into the non-parasitized RBCs ranged between 35% and 45%, while that into parasitized RBCs was between 51% and 72%. The results suggested that artemisinin and selected derivatives were preferentially distributed in parasitized RBCs. A Multiple Linear Regression model was built to gain insight about the essential structural properties required for the uptake of this class of compounds in parasitized RBCs and will provide instruction for designing of new derivatives of this class of compounds with improved uptake.

Determination of a novel paclitaxel derivative (NPD-103) in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry.

A sensitive and specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for quantification of a newly developed anticancer agent NPD-103 has been established. An aliquot of human plasma sample (200 microL) was spiked with (13)C-labeled paclitaxel (internal standard) and extracted with 1.3 mL of tert-butyl methyl ether. NPD-103 was quantitated on a C(18) column with methanol-0.1% formic acid (75:25, v/v) as mobile phase using UPLC-MS-MS operating in positive electrospray ionization mode with a total run time of 3.0 min. For NPD-103 at the concentrations of 1.0, 5.0 and 10.0 microg/mL in human plasma, the absolute extraction recoveries were 95.58, 102.43 and 97.77%, respectively. The linear quantification range of the method was 0.1-20.0 microg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra- and inter-day accuracy for NPD-103 at 1.0, 5.0 and 10.0 microg/mL levels in human plasma fell into the ranges of 95.29-100.00% and 91.04-94.21%, and the intra- and inter-day precisions were in the ranges of 8.96-11.79% and 7.25-10.63%, respectively. This assay is applied to determination of half-life of NPD-103 in human plasma.

Determination of a novel epothilone D analog (AV-EPO-106) in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry.

A novel ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been established for the determination of a newly synthesized epothilone D analog (AV-EPO-106) in human plasma. The plasma samples were prepared by liquid-liquid extraction with cold tert-butyl methyl ether. The chromatographic separation was achieved within 5 min on a C(18) column with water-methanol (10:90, v/v) as mobile phase at a flow-rate of 0.8 mL/min. Mass transition of m/z 568.2 to 386.1 was measured for AV-EPO-106 in positive atmospheric pressure chemical ionization mode. A detailed validation of the method was performed as per the USFDA guidelines. For AV-EPO-106 at the concentrations of 1.0, 5.0 and 10.0 microg/mL in human plasma, the absolute extraction recoveries were 86.17, 85.24 and 85.69%, respectively. The linear quantification range of the method was 0.10-20.0 microg/mL in human plasma with linear correlation coefficients greater than 0.999. The intra-day and inter-day accuracy for AV-EPO-106 at the levels of 1.0, 5.0 and 10.0 microg/mL in human plasma fell in the ranges of 98.25-100.47 and 94.19-97.25%, and the intra- and inter-day precision were in the ranges of 4.75-6.30% and 8.89-10.45%, respectively. The method was successfully applied to quantify AV-EPO-106 in human plasma to determine the half-life of this compound in human plasma.