Screening of blood-activating active components from Curcuma wenyujin Y.H. Chen et C. Ling rhizome based on spectrum-effect relationship analysis and network pharmacology.

Curcuma wenyujin Y.H. Chen et C. Ling rhizome (also called EZhu in China) has long been used as plant medicine for its traditional effect on promoting blood circulation and remove blood stasis. However, the active components of EZhu are still unclear at present. This research is managed to investigate the pharmacodynamics material basis on removing blood stasis of EZhu by exploring the spectrum-effect relationship between UPLC-Q/TOF-MS fingerprints and pharmacologic actions. Hemorheology and related functional parameters were detected to evaluate the pharmacologic actions of EZhu. Relative content Changes of components in rat plasma were detected by UPLC-Q/TOF-MS. A compound-target-pathway network was built to predict the pharmacological activity of components in plasma. Then, bivariate correlation analysis (BCA) was used to explore the correlation degree between components in plasma and pharmacologic actions of EZhu. In UPLC-Q/TOF-MS fingerprints of rat plasma, 10 prototype components were identified. BCA results show that 8 components were concerned with the pharmacological activity for treating blood stasis syndrome (BSS) in varying degrees (R > 0.5, P < 0.05). Among them, zedoarofuran and curzerenone have shown correlation with more pharmacological indicators. The network predicted that 80 targets were closely related to 10 components, in which 48 targets were connected with 159 metabolic pathways including arachidonic acid metabolism, sphingolipid signaling pathway, and linoleic acid metabolism. Overall, this study provided a scientific basis for TCM quality control to ensure its safety and efficacy.

Serum Proteomic Analysis of Cannabis Use Disorder in Male Patients.

Cannabis use has been growing recently and it is legally consumed in many countries. Cannabis has a variety of phytochemicals including cannabinoids, which might impair the peripheral systems responses affecting inflammatory and immunological pathways. However, the exact signaling pathways that induce these effects need further understanding. The objective of this study is to investigate the serum proteomic profiling in patients diagnosed with cannabis use disorder (CUD) as compared with healthy control subjects. The novelty of our study is to highlight the differentially changes proteins in the serum of CUD patients. Certain proteins can be targeted in the future to attenuate the toxicological effects of cannabis. Blood samples were collected from 20 male individuals: 10 healthy controls and 10 CUD patients. An untargeted proteomic technique employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was employed in this study to assess the differentially expressed proteins. The proteomic analysis identified a total of 121 proteins that showed significant changes in protein expression between CUD patients (experimental group) and healthy individuals (control group). For instance, the serum expression of inactive tyrosine protein kinase PEAK1 and tumor necrosis factor alpha-induced protein 3 were increased in CUD group. In contrast, the serum expression of transthyretin and serotransferrin were reduced in CUD group. Among these proteins, 55 proteins were significantly upregulated and 66 proteins significantly downregulated in CUD patients as compared with healthy control group. Ingenuity pathway analysis (IPA) found that these differentially expressed proteins are linked to p38MAPK, interleukin 12 complex, nuclear factor-κB, and other signaling pathways. Our work indicates that the differentially expressed serum proteins between CUD and control groups are correlated to liver X receptor/retinoid X receptor (RXR), farnesoid X receptor/RXR activation, and acute phase response signaling.

3,3'-Diindolylmethane Exhibits Significant Metabolism after Oral Dosing in Humans.

3,3'-Diindolylmethane (DIM), a major phytochemical derived from ingestion of cruciferous vegetables, is also a dietary supplement. In preclinical models, DIM is an effective cancer chemopreventive agent and has been studied in a number of clinical trials. Previous pharmacokinetic studies in preclinical and clinical models have not reported DIM metabolites in plasma or urine after oral dosing, and the pharmacological actions of DIM on target tissues is assumed to be solely via the parent compound. Seven subjects (6 males and 1 female) ranging from 26-65 years of age, on a cruciferous vegetable-restricted diet prior to and during the study, took 2 BioResponse DIM 150-mg capsules (45.3 mg DIM/capsule) every evening for one week with a final dose the morning of the first blood draw. A complete time course was performed with plasma and urine collected over 48 hours and analyzed by UPLC-MS/MS. In addition to parent DIM, two monohydroxylated metabolites and 1 dihydroxylated metabolite, along with their sulfate and glucuronide conjugates, were present in both plasma and urine. Results reported here are indicative of significant phase 1 and phase 2 metabolism and differ from previous pharmacokinetic studies in rodents and humans, which reported only parent DIM present after oral administration. 3-((1H-indole-3-yl)methyl)indolin-2-one, identified as one of the monohydroxylated products, exhibited greater potency and efficacy as an aryl hydrocarbon receptor agonist when tested in a xenobiotic response element-luciferase reporter assay using Hepa1 cells. In addition to competitive phytochemical-drug adverse reactions, additional metabolites may exhibit pharmacological activity highlighting the importance of further characterization of DIM metabolism in humans. SIGNIFICANCE STATEMENT: 3,3'-Diindolylmethane (DIM), derived from indole-3-carbinol in cruciferous vegetables, is an effective cancer chemopreventive agent in preclinical models and a popular dietary supplement currently in clinical trials. Pharmacokinetic studies to date have found little or no metabolites of DIM in plasma or urine. In marked contrast, we demonstrate rapid appearance of mono- and dihydroxylated metabolites in human plasma and urine as well as their sulfate and glucuronide conjugates. The 3-((1H-indole-3-yl)methyl)indolin-2-one metabolite exhibited significant aryl hydrocarbon receptor agonist activity, emphasizing the need for further characterization of the pharmacological properties of DIM metabolites.

Qualitative, quantitative, and pharmacokinetic study on the absorbed components of Ardisia japonica (Thunb.) Blume in rat plasma based on molecular networking combined with quadrupole time-of-flight LC/MS and triple quadrupole LC/MS.

Isolation and screening of different compounds from plant extracts are always the key for natural drug research, and the absorbed prototype components have been considered as potential active ingredients. UHPLC combined with quadrupole time-of-flight mass spectrometry (Q-TOF-LC/MS) has been widely used in the research of natural drugs; however, we still need a more effective tool to compare and treat from a raw data. In this study, we provided a fast analytical method to measure the absorbed prototype components and their metabolites both qualitatively and quantitatively based on molecular networking (MN). For example, in Ardisia japonica (Thunb.) Blume, a total of eight absorbed prototype components in rat plasma were identified. Furthermore, pharmacokinetic study was also successfully performed on the eight absorbed prototype components in rat plasma. Our findings have provided important information on the investigation of A. japonica in vivo. More importantly, the MS network analysis pattern serves as an integral solution for qualitative and quantitative determination of phytochemical compounds in natural drugs.

UPLC-MS/MS Method for the Simultaneous Quantification of Eight Compounds in Rat Plasma and Its Application to a Pharmacokinetic Study after Oral Administration of Veratrum (Veratrum nigrum L.) Extract.

Veratrum nigrum L. is a well-known traditional Chinese medicine with a lot of pharmacological activities including antihypertensive, anticancer, and antifungal effects. In the current experiment, a rapid and sensitive UPLC-MS/MS method that takes only 7 min run time has been established and validated for simultaneous determination of eight bioactive compounds including cyclopamine, jervine, veratramine, polydatin, quercetin, apigenin, resveratrol, and veratrosine in rat plasma. The chromatographic separation of analytes and internal standard was performed on a Phenyl-Hexyl column (2.1 × 100 mm, 1.7 µm) with the mobile phase consisting of water (0.1% formic acid) and acetonitrile at a flow rate of 0.3 mL/min. An electrospray ionization (ESI) source was used to detect the samples in both positive and negative ion modes. The intra- and interday precisions of the compounds were less than 9.5% and the accuracy ranged from -10.8% to 10.4%. The extraction recoveries of the compounds were in the range of 85.1 ± 1.5% to 102.6 ± 8.0%, and the matrix effect ranged from 91.2 ± 4.5% to 113.8 ± 1.5%. According to the results of the stability test, the eight compounds have good stability under various conditions and the relative standard deviation (RSD) less than 13.2%. The pharmacokinetic parameters of the eight compounds in rat plasma after oral administration of Veratrum nigrum L. extract were successfully determined by the established UPLC-MS/MS method.

UHPLC-MS/MS method for pharmacokinetic and bioavailability determination of five bioactive components in raw and various processed products of Polygala tenuifolia in rat plasma.

CONTEXT: Sibiricose A5 (A5), sibiricose A6 (A6), 3,6'-disinapoyl sucrose (DSS), tenuifoliside A (TFSA) and 3,4,5-trimethoxycinnamic acid (TMCA) are the main active components of Polygala tenuifolia Willd. (Polygalaceae) (PT) that are active against Alzheimer's disease. OBJECTIVE: To compare the pharmacokinetics and bioavailability of five active components in the roots of raw PT (RPT), liquorice-boiled PT (LPT) and honey-stir-baked PT (HPT). MATERIALS AND METHODS: The median lethal dose (LD50) was evaluated through acute toxicity test. The pharmacokinetics of five components after oral administration of extracts of RPT, LPT, HPT (all equivalent to 1.9 g/kg of RPT extract for one dose) and 0.5% CMC-Na solution (control group) were investigated, respectively, in Sprague-Dawley rats (four groups, n = 6) using UHPLC-MS/MS. In addition, the absolute bioavailability of A5, A6, DSS, TFSA and TMCA after oral administration (7.40, 11.60, 16.00, 50.00 and 3.11 mg/kg, respectively) and intravenous injection (1/10 of the corresponding oral dose) in rats (n = 6) was studied. RESULTS: The LD50 of RPT, LPT and HPT was 7.79, 14.55 and 15.99 g/kg, respectively. AUC 0- t of RPT, LPT and HPT were as follows: A5 (433.18 ± 65.48, 680.40 ± 89.21, 552.02 ± 31.10 ng h/mL), A6 (314.55 ± 62.73, 545.76 ± 123.16, 570.06 ± 178.93 ng h/mL) and DSS (100.30 ± 62.44, 232.00 ± 66.08, 197.58 ± 57.37 ng h/mL). The absolute bioavailability of A5, A6, DSS, TFSA and TMCA was 3.25, 2.95, 2.36, 1.17 and 42.91%, respectively. DISCUSSION AND CONCLUSIONS: The pharmacokinetic and bioavailability parameters of each compound can facilitate future clinical studies.

[Effects of gut microbiota on five absorbed components of Berberis kansuensis in rat serum by HPLC-QqQ-MS].

To elucidate the absorption and metabolism of alkaloids in Berberis kansuensis in vivo, a high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-QqQ-MS) method was developed to qualitatively and quantitatively analyze the absorption components in rat serum in multiple-reaction monitoring mode. The mobile phase consisted of 0.1% formic acid and acetonitrile with a gradient elution mode. In addition, to investigate the effects of gut microbiota on five absorbed components of B. kansuensis in rat serum, diabetic rat and pseudo germ-free diabetic rat models were established, and partial least squares discriminant analysis and One-way ANOVA were used to study the content differences of five components among different groups. In this study, a HPLC-QqQ-MS method for quantitative analysis of five components in rat serum after oral administration of B. kansuensis was established for the first time. It was found that there were differences in the five constituents in rat serum between different groups. By comparing the normal group with the diabetic model group, we found that the absorption and metabolism capacities of berberine and magnoflorine were different under the health and pathological conditions. It was also found that the serum levels of berberine, magnoflorine and jatrorrhizine in pseudo germ-free diabetic rats were significantly lower than those in diabetic rats, indicating that gut microbiota plays an important role in the metabolism of alkaloids of B. kansuensis in vivo. These results provide a good reference for clarifying the active ingredients of B. kansuensis in the treatment of diabetes.

Comparative Study on Pharmacokinetics of Four Active Compounds in Rat Plasma after Oral Administration of Raw and Wine Processed Chuanxiong Rhizoma.

In Chinese medicine, the effect of promoting blood circulation and removing stasis could be enhanced after Chuanxiong Rhizoma is processed by wine. However, the relevant mechanism remains unclear. In this manuscript, a rapid and sensitive quantification method employing ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established and validated to simultaneously determine butylidenephthalide, ligustilide, senkyunolide A and ferulic acid in rat plasma after oral administration of raw Chuanxiong Rhizoma (RCR) and wine-processed Chuanxiong Rhizoma (WCR) respectively. All analytes were extracted from plasma by proteins precipitation with methanol. Chromatographic separation was carried out on a Hypersil GOLD C18 column by using a gradient mobile phase system of acetonitrile and water with 0.01% formic acid, the flow rate was 0.3 mL/min. For exact mass detecting, quick switching mode was used, positive and negative ions could be detected in one injection. The pharmacokinetic profiles of four components in the two groups were evaluated and compared. The results showed that, compared to the RCR group, the Vd and AUC0→t values of four active compounds were increased and decreased respectively in WCR group, which revealed the effect of wine processing to Chuanxiong Rhizoma: the stronger the effect, the wider the distribution.

Hyphenated chromatography detection and compound-target-disease investigation on herb-pair Chuanxiong Rhizoma - Xiangfu Rhizoma.

ETHNOPHARMACOLOGY RELEVANCE: The combination of Chuanxiong Rhizoma (Ligusticum chuanxiong Hort., umbelliferae) with Xiangfu Rhizoma (the rhizoma of Cyperus rotundus L., Cyperaceae), is deemed as CR-XR herb-pair (Yaodui) in China. Their compatible mechanism needs a further research using modern analytical techniques and bioinformatic tool. METHODS: Head Space- Solid Phase Micro Extraction coupled with Gas Chromatography/Mass Spectrometer detection (HS-SPME-GC/MS) and Liquid Chromatography coupled to quadrupole Time of Flight - Mass Spectrometry (LC-qTOF-MS) were applied in an accurate identification of the absorbed phytochemicals in mice serum; Their potential targets were available after compound-protein interaction (CPI) prediction and molecular docking verification; Then the corresponding disease types, as well as the relevant Traditional Chinese Medicine (Zhongyi) syndromes (Zheng), were matched from databases and references. RESULTS: Resolution from hyphenated chromatographic datasets, thirty-eight phytochemicals were detected in serum samples from mice. Seventy potential target proteins were thereby found through a bioinformatic calculation, which mainly focused on circulatory, endocrine and nervous diseases in Western medicine, also related with Qizhi and Xueyu Zheng from the perspective of Zhongyi. Part of the relationships among compound-Target-Disease have been confirmed by literatures. These virtual data were sketched out as 'The active Compound - potential Target' network, 'Target - Disease' network and 'Target - Zhongyi Disease' network, in which the network topology was used to analyze them. CONCLUSIONS: Our work successfully explained the compatible mechanism of CR-XR Yaodui, which exert 'multi-components, multi targets' in treating Qizhi and Xueyu Zheng.

Mixing Ginkgo biloba Extract with Sesame Extract and Turmeric Oil Increases Bioavailability of Ginkgolide A in Mice Brain.

Ginkgo biloba extract (GBE) is widely used as herbal medicine. Preventive effect of GBE against dementia, including Alzheimer's disease, has been reported. The bioactive compounds in GBE that impart these beneficial effects, flavonoids and terpene lactones, have poor bioavailability. Our previous study found distribution of bioactive compounds of sesame extract in mice brain after mixing it with turmeric oil. Here, we evaluate the distribution of bioactive compounds of GBE by combining it with the mixture of sesame extract and turmeric oil (MST). The content of terpene lactones in mice serum was significantly increased in a dose-dependent manner after administration of GBE. However, the contents of terpene lactones in mice brain were not significantly changed. Concentration of ginkgolide A in mice brain increased significantly when GBE was co-administrated with MST than when GBE was administered alone. These results suggest that MST may be effective in enhancing the bioavailability of ginkgolide A in GBE.

[UPLC-Q-TOF-MS/MS analysis on prototypes components and metabolites of effective fractions of Polygonum orientale flower in rat serum and urine].

Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS) method was applied to analyze the prototypes and metabolites of the effective components of Polygonum orientale in SD rat serum and urine. The separation was performed on Agilent Eclipse Plus C_(18) column( 2. 1 mm×100 mm,1. 8 µm),with 0. 1% formic acid solution( A)-acetonitrile( B) as the mobile phase for gradient elution. Mass spectrometry data of biological samples were obtained under positive and negative electrospray ion mode. By comparing chromatogram differences between blank samples and drug treatment samples,prototype components and metabolites of the effective components of P. orientale extract were identified. The results showed that 12 metabolites were detected in serum and 26 metabolites in urine( including cross-components) of rats. The main metabolic pathways included hydrogenation,hydroxylation,glucuronidation,sulfation reaction,and methylation-glucuronidation,etc. The method established in this study was reliable and effective for studying the metabolic characteristics of the effective components of P. orientale in rats,and it can provide a reference for further studies on therapeutic material basis of this herb.

Pharmacokinetic properties of phytochemicals in Hypericum perforatum influence efficacy of regulating oxidative stress.

BACKGROUND: Hypericum perforatum is used in ethnopharmacology and has recently become popular in conventional medicine for treatment of mild to moderate depression. The abundance of potentially functional phytochemicals and their broader utilizations in traditional medicine suggests that ingestion of H. perforatum may impart additional secondary health benefits. HYPOTHESIS/PURPOSE: Considering that many phytochemicals are known to display antioxidant activity, it was hypothesized that H. perforatum ingestion may inhibit oxidative stress and inflammation (OSI) which occurs in transient cycles following exercise and consumption of meals. The aim of this study was to explore the pharmacokinetics of H. perforatum phytochemicals after ingestion to predict the absorption timing of putative medicinal phytochemicals. STUDY DESIGN/METHODS: In silico analyses of previously published plant extract phytochemical profiles were performed, wherein the Phytochemical Absorption Prediction (PCAP) model was used to predict the pharmacokinetics of phytochemicals. The predicted times for phytochemicals to reach maximum plasma concentration (Tmax), and associated antioxidant activities, were compared to prior clinical in vivo studies to assess the accuracy and applicability of predictions. RESULTS: The PCAP model identified that phytochemicals with antioxidant activity concurrently accumulate in plasma with Tmax in the range of 1.6-2.3 h after ingestion. Comparison with previously published results identified that attenuation of OSI following H. perforatum ingestion aligns with the predicted Tmax of antioxidant phytochemicals. CONCLUSION: Based on these results it is therefore recommended that H. perforatum administration occurs 2 h before meals to provide optimal secondary health benefits associated with inhibition of postprandial stress. Additionally, these results highlight the use of in silico analyses to inform ingestion time and optimize the health benefits from ingestion of plant-based foods and medicines.

Multivitamin and Mineral Supplementation Containing Phytonutrients Scavenges Reactive Oxygen Species in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Phytonutrients and vitamin and mineral supplementation have been reported to provide increased antioxidant capacity in humans; however, there is still controversy. In the current clinical trial, we examined the antioxidant and DNA protection capacity of a plant-based, multi-vitamin/mineral, and phytonutrient (PMP) supplementation in healthy adults who were habitually low in the consumption of fruits and vegetables. This study was an eight-week, double-blind, randomized, parallel-arm, and placebo-controlled trial. PMP supplementation for eight weeks reduced reactive oxygen species (ROS) and prevented DNA damage without altering endogenous antioxidant system. Plasma vitamins and phytonutrients were significantly correlated with ROS scavenging and DNA damage. In addition, gene expression analysis in PBMC showed subtle changes in superoxide metabolic processes. In this study, we showed that supplementation with a PMP significantly improved ROS scavenging activity and prevented DNA damage. However, additional research is still needed to further identify mechanisms of actions and the role of circulating phytonutrient metabolites.

In vitro metabolism of selected bioactive compounds of Eurycoma longifolia root extract to identify suitable markers in doping control.

Eurycoma longifolia Jack (Tongkat Ali, Simaroubaceae) is a medicinal plant endemic to South-East Asia. For centuries, different parts of the plant have been used as a natural remedy to treat fever, hypertension, or sexual insufficiency. Today, Eurycoma longifolia preparations are commercially available and advertised to enhance athletic performance and muscle strength. Several studies have demonstrated a testosterone-boosting effect that might be caused by the release of free testosterone from the sex-hormone-binding globulin. To date, many phytochemical constituents of Eurycoma longifolia root extracts have been identified and physiological effects have been examined, while studies on their biotransformation and monitoring are still lacking. Within this study, eurycomalide C, eurycomalactone, 5,6-dehydro-eurycomalactone, longilactone, 14,15ß-dihydroklaieanone, 11-dehydroklaieanone, 9-hydroxycanthin-6-one, and 9-methoxycanthin-6-one isolated from E. longifolia root were incubated with liver microsomes. Respective metabolites were analyzed by liquid chromatography-tandem (high-resolution) mass spectrometry. The compounds were chosen based on their potential androgenic effects (estimated by in vitro assays), their concentrations in plant extracts, and presumptive metabolic pathways. Hydroxylated phase I metabolites were only observed for 5,6-dehydro-eurycomalactone, 11-dehydroklaieanone, 9-hydroxycanthin-6-one, and 9-methoxycanthin-6-one. Moreover, an O-demethylated metabolite of 9-methoxycanthin-6-one was found. Besides, the glucuronide of 9-hydroxycanthin-6-one was detected after in vitro glucuronidation using liver microsomes. The in vitro generated metabolites were comparable to that detected in urine and serum after a single ingestion of either 9-methoxycanthin-6-one or an Eurycoma longifolia root extract. Hence, 9-methoxycanthin-6-one, its glucuronide, and the glucuronide of its O-demethylated biotransformation product are proposed to be the most suitable targets for detection of 9-methoxycanthin-6-one or Tongkat Ali application in urine and serum.

Simultaneous determination of fourteen compounds of Hedyotis diffusa Willd extract in rats by UHPLC-MS/MS method: Application to pharmacokinetics and tissue distribution study.

A rapid, sensitive and selective ultra high-performance liquid chromatography-tandem mass spectrometry UHPLC-MS/MS method has been developed and validated for the simultaneous determination of fourteen bioactive ingredients (gallic acid, geniposidic acid, protocatechuic acid, caffeic acid, ferulic acid, scopoletin, apigenin-7-o-glucuronide, daidzein, apigenin, ursolic acid, oleanolic acid, ß-sitosterol, coniferin, and stigmasterol) in the plasma and tissues of rats. Danshensu and icariin were used as internal standards (IS1 and IS2). The chromatographic separation was achieved by using an Agilent ZORBAX RRHD Eclipse Plus C18 column (2.1 mm × 50 mm, 1.8 µm) with gradient elution using mobile phase, which consisted of 0.1% acetic acid water (solvent A) and methanol (solvent B) and pumped at a flow rate of 0.3 mL/min. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode utilizing electrospray ionization (ESI) in positive and negative mode. The plasma samples were pretreated via protein precipitation with 300 µL of methanol containing 0.1% (v/v) formic acid and organ homogenates were processed by solid-phase extraction (SPE) with Waters Oasis HLB 3 cc (60 mg), respectively. The intra- and inter- day precisions (RSD%) were less than 10.3%, while the accuracy was ranged from -7.34% to 9.10%. Extraction recovery ranged from 85.02 to 112.0% and the matrix effects ranged from 85.12% to 109.6%. The present method exhibited excellent linearity and the lower limits of quantification (LLOQ) were 30.0 ng/mL, 15.0 ng/mL, 80.0 ng/mL, 30.0 ng/mL, 10.0 ng/mL, 3.0 ng/mL, 2.5 ng/mL, 2.5 ng/mL, 1.5 ng/mL, 15.0 ng/mL, 75.0 ng/mL, 15.0 ng/mL, 30.0 ng/mL, and 20.0 ng/mL for gallic acid, protocatechuic acid, geniposidic acid, caffeic acid, ferulic acid, scopoletin, apigenin-7-o-glucuronide, daidzein, apigenin, ursolic acid, oleanolic acid, ß-sitosterol, coniferin, and stigmasterol, respectively. This analytical method was verified by the FDA guidelines for bioanalytical method validation and applied to investigate the pharmacokinetics and biodistribution of fourteen constituents of Hedyotis diffusa Willd extract in rats. These results provide useful information for improving the pharmacokinetics and biodistribution of fourteen bioactive ingredients of Hedyotis diffusa Willd extract in SD rats, supporting additional clinical application and Chinese herbal medicine safety evaluations.

Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A Randomized, Double Blind, Placebo Controlled Study.

The primary objective of this clinical study was to evaluate the effect of a dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood nutrient status and biomarkers of heart health risk in a Russian population. One hundred twenty healthy adults (40-70 years) were recruited for a 56-day (eight-week) randomized, double blind, placebo controlled study with parallel design. Subjects were divided into two groups and received either a VMP or a placebo (PLA) supplement. Blood nutrient levels of ß-carotene, α-tocopherol, vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured at baseline and on Days 28 and 56, and quercetin was measured at baseline and on Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high-sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl transferase (GGT), uric acid and blood lipid profile, were measured at baseline and Day 56. Dietary VMP supplementation for 56 days significantly increased circulating levels of quercetin, vitamin C, RBC folate and partially prevented the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were significantly reduced (-3.97 ± 10.09 µmol/L; -1.68 ± 14.53 U/L, respectively) after VMP supplementation compared to baseline. Dietary VMP supplementation improved the nutrient status and reduced biomarkers of heart health risk in a Russian population.

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial.

BACKGROUND: Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. METHODS: A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. DISCUSSION: Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03166540 . Registered on May 21, 2017.

Determination of the phytochemical composition of Jingning fang and the in vivo pharmacokinetics of its metabolites in rat plasma by UPLC-MS/MS.

Jingning fang (JNF) is an effective Traditional Chinese Medicine (TCM) which is used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). To clarify the bioactive constituents of JNF, a Thermo Q Exactive™ Plus Orbitrap™ mass spectrometer was used in this study. More than 127 chemical compounds were isolated and identified tentatively in the JNF extract, while 42 prototype constituents with 4 potential metabolites were identified tentatively in rat plasma. A method for simultaneous determination of polygalaxanthone III (PAIII), sibiricose A5 (A5), sibiricose A6 (A6), 3, 6'-disinapoyl sucrose (3,6'-DISS), tenuifoliside C (TEC), tenuifolin B (TNB), verbascoside (VCE), heterophyllin B (HEB) and schisandrin (SCH) in rat was developed and validated using polydatin (PLN) and psoralen (PSN) as internal standards. All calibration curves proved favorable linearity (R2≥0.9923) in linear ranges. The lower limit of quantification (LLOQ) was 2.5ng/mL for PAIII, A5, 3, 6'-DISS, TNB, VCE, HEB and SCH, 1.0ng/mL for A6 and TEC, respectively. Intra-day and inter-day precisions didn't exceed 14.0% for all the analytes. Extraction recoveries and matrix effects of analytes and IS were acceptable. The validated method has been successfully applied to the pharmacokinetics (PK) studies of the nine compounds in JNF. These findings are useful for predicting the bioactive components of JNF, and will aid in optimizing dose regimens of the drug.

Lipid-lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel.

In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.

A Critical Review on Polyphenols and Health Benefits of Black Soybeans.

Polyphenols are plant secondary metabolites containing antioxidant properties, which help to protect chronic diseases from free radical damage. Dietary polyphenols are the subject of enhancing scientific interest due to their possible beneficial effects on human health. In the last two decades, there has been more interest in the potential health benefits of dietary polyphenols as antioxidant. Black soybeans (Glycine max L. Merr) are merely a black variety of soybean containing a variety of phytochemicals. These phytochemicals in black soybean (BSB) are potentially effective in human health, including cancer, diabetes, cardiovascular diseases, cerebrovascular diseases, and neurodegenerative diseases. Taking into account exploratory study, the present review aims to provide up-to-date data on health benefit of BSB, which helps to explore their therapeutic values for future clinical settings. All data of in vitro and in vivo studies of BSB and its impact on human health were collected from a library database and electronic search (Science Direct, PubMed, and Google Scholar). The different pharmacological information was gathered and orchestrated in a suitable spot on the paper.