Iridoid- and flavonoid-enriched fractions of Cornus sanguinea and Cornus mas exert antioxidant and anti-inflammatory effects and inhibit key enzymes in the treatment of metabolic disorders.

Background: Berry fruits are recognized as a "superfood" due to their high content of bioactive compounds and health benefits. Scope and approach: Herein, extracts of Cornus sanguinea and Cornus mas fresh and dried fruits obtained by different extraction procedures (ethanolic and hydroalcoholic maceration, ultrasound-assisted extraction, and Soxhlet apparatus) were analysed using liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-QTOF-MS) and compared to identify the main healthy compounds and their impact on the inhibition of key enzymes (pancreatic lipase, α-glucosidase, and α-amylase) associated with metabolic disorders. The antioxidant activity and inhibition of nitric oxide (NO) and NF-κB pathway were also investigated. Key findings and conclusions: Flavonoids, iridoids, and phenolic acids were the main classes of identified compounds. Herein, kaempferol 3-O-galactoside, kaempferol 3-O-glucoside, quercetin, quercetin 3-O-xyloside, and myricetin 3-O-galactoside were detected for the first time in C. sanguinea. Remarkable antioxidant effects and promising α-glucosidase and lipase inhibitory activity were observed with extracts obtained by hydroalcoholic maceration of both Cornus dried fruits. Consequently, these extracts were subjected to fractionation using Amberlite XAD-16 resin. The most promising biological activities, which are attributed to the presence of some flavonoids and iridoids, were detected with the C. sanguinea fractions, in particular SD2(II). The results of this study offer new insights into the potential development of functional foods, nutraceuticals, and food supplements using the Cornus species.

Volatile fingerprints of different parts of Chongming saffron (Crocus sativus) flowers by headspace-gas chromatography-ion mobility spectrometry and in vitro bioactive properties of the saffron tepals.

In this work, the volatile fingerprints of different parts of Chongming saffron flowers (stigmas, stamens, and tepals) were analyzed and compared for the first time by headspace-gas chromatography-ion mobility spectrometry. Three different parts of saffron flowers could be clearly distinguished using principal component analysis based on signal intensity data of gas chromatography-ion mobility spectrometry. Therefore, gas chromatography-ion mobility spectrometry coupled with principal component analysis method could be employed as a new method for authentication and quality control of saffron for the reason of frequent addition with stamens and/or tepals as adulterants in saffron. Moreover, the bioactive composition (total flavonoids, total phenolics, and total anthocyanins) and bioactive properties of saffron tepals were evaluated. The results indicated that aqueous, ethanol, and ethyl acetate extracts of saffron tepals exhibited good radical scavenging (2,2-Diphenyl-1-picrylhydrazyl, ABTS, and OH) and enzyme (α-amylase/α-glucosidase) inhibition activities, which probably were attributed to the bioactive components contained in the extracts. This approach would provide the important information for monitoring the quality of saffron as well as exploring the utilization of saffron tepals in functional food technology. PRACTICAL APPLICATION: This study demonstrated that the HS-GC-IMS method might be used as a new strategy for quality control of saffron, and the saffron tepals were rich source of bioactive components that could be used in health-promoting products.

Chemical characterization of the antioxidant and α-glucosidase inhibitory active fraction of Malus transitoria leaves.

Chinese Tibetan tea made from the tender leaves of Malus transitoria is a widely consumed health drink, but there are few reports on its chemical composition and biological activity. In this study, we found that a 50% ethanol extract of M. transitoria had good antioxidant and α-glucosidase inhibitory activities in vitro. Guided by in vitro bioassays, chromatographic separation and purification were conducted, and the most active fraction in M. transitoria was determined. UPLC-Orbitrap-MS/MS was used to further quickly and comprehensively characterize the chemical composition. Library searches, MS/MS fragmentation patterns of two isolated reference compounds, and bibliography were used to annotate 81 compounds, of which 2 were new compounds, and 79 were identified from M. transitoria for the first time. This study provides a scientific basis for the development of antioxidant and anti-diabetic functional foods from M. transitoria.

Steroidal saponins from Trillium govanianum as α-amylase, α-glucosidase, and dipeptidyl peptidase IV inhibitory agents.

OBJECTIVE: To provide the scientific basis for the utility of rhizome of Trillium govanianum as nutraceutical supplements in managing physiological glycemic levels. METHODS: The in vitro enzyme inhibitory activity of the extract, fractions, and the isolated steroidal saponins from the rhizome part of T. govanianum was carried out against α-amylase, α-glucosidase, and dipeptidyl peptidase IV. The molecular interactions, binding score, and pharmacokinetic parameters (absorption, distribution metabolism, and excretion) of steroidal saponins were analyzed by the Schrodinger molecular docking software. KEY FINDINGS: Current study explained that the extract, fractions, and isolated steroidal saponins from T. govanianum possess good α-amylase and α-glucosidase inhibitory activity while moderate dipeptidyl peptidase IV inhibitory activity. Moreover, in vitro results revealed that borassoside E (IC50 7.15 ± 1.78 µM), protodioscin (IC50 6.72 ± 0.04 µM), and diosgenin (IC50 12.75 ± 2.70 µM) are most effective in inhibiting the activity of α-amylase, α-glucosidase, and dipeptidyl peptidase IV, respectively. Current in silico and in vitro studies established an association between the steroidal saponins from T. govanianum and their molecular interactions with α-amylase, α-glucosidase, and dipeptidyl peptidase IV. CONCLUSION: The results of this investigation suggest that fractions and steroidal saponins from T. govanianum exhibit good antidiabetic activity which could be used as nutraceutical supplements for the management of systemic glucose level.

Use of a deoxynojirimycin-fluorophore conjugate as a cell-specific imaging probe targeting α-glucosidase on cell membranes.

Molecules designed for cell-specific imaging were studied, taking advantage of an enzyme-inhibitor interaction. 1-Deoxynojirimycin (DNJ) can be actively captured by cells which express the surface membrane protein α-glucosidase. New probes composed of DNJ for recognition linked to a fluorophore signal portion were prepared (DNJ-CF31, DNJ-Dans 2 and DNJ-DEAC 3). Docking simulations revealed that the inhibitors acarbose and miglitol and the inhibitor portion of the probes bind at the same position in the pocket of α-glucosidase (human-derived PDB: 3TON). The ability of probes 1-3 to detect the difference between HeLa cells (from human cervical cancer tissue), Neuro-2a cells (from a mouse neuroblastoma C1300 tumor), N1E-115 cells (from a mouse brain neuroblastoma C1300 tumor), A1 cells (from the astrocyte of a newborn mouse brain), and Caco-2 cells (from a human colon carcinoma) was evaluated, and cell-specific fluorescence imaging was possible for conjugate probes 1 and 2. Caco-2 cells treated with probes 1 and 2 showed blue and green fluorescence, respectively, from the cell membrane, and did not stain the Caco-2 cells inside. These results show that DNJ-CF31 and DNJ-Dans 2 recognize an α-glucosidase protein on the surface of Caco-2 cells. Probes 1 and 2 did not stain any part of the other cells. This cell-specific imaging strategy is applicable for a variety of therapeutic agents for many diseases.

Seminal plasma neutral alpha-glucosidase activity as an early predictor of patency and natural pregnancy after microsurgical vasoepididymostomy.

Microsurgical vasoepididymostomy (MVE) is recommended as a first-line option for treatment of epididymal obstructive azoospermia (EOA). However, early indicators for predicting patency and natural pregnancy are unclear. Our aim was to explore the early predictive value of seminal plasma neutral alpha-glucosidase (NAG) activity for patency and natural pregnancy after MVE. Eighty-four patients with EOA who underwent MVE were enrolled in this study. The post-operative patency and natural pregnancy rates were 60.71% and 33.33% respectively. The presence of motile epididymal spermatozoa at the anastomosis site and NAG activity measured at the first month after MVE were early and independent predictors of patency and natural pregnancy. The areas under the receiver operating characteristic curves (AUCs) of NAG activity for prediction of patency and natural pregnancy were 0.78 (95% confidence interval [CI]: 0.68-0.88) and 0.82 (95% CI: 0.73-0.92). The best cut-off values of NAG activity for predicting patency and pregnancy were 15.9 and 17.0 m IU/ejaculate respectively. In conclusion， NAG activity measured at the first month after MVE is an early and independent predictor of patency and natural pregnancy.

Influence of preparation procedures on the phenolic content, antioxidant and antidiabetic activities of green and black teas

The influence of common tea preparation procedures (temperature, infusion time, consumption time interval and tea bag/loose-leaf) and the type of water used, on the total phenolic content (TPC), the radical scavenging activity and the α-glucosidase inhibitory activity were assessed. Higher TPC and antioxidant activity were obtained when using lower mineralized waters. Tea bags also evidenced higher antioxidant activity than loose-leaf samples. Under the same conditions (90 ºC and five minutes of infusion time) green tea contains almost twice the quantity of polyphenols and the free radical scavenging ability of black tea. In the α-glucosidase assay all infusions were active (97-100 %). Furthermore, HPLC allowed to identify some of the polyphenols present in both teas and to monitor their composition change with time. After twenty-four hours, the antioxidant activity was maintained without significant changes, but a small decrease in enzyme inhibition was observed, although this activity was still very high

Metabolic Impacts of Maltase Deficiencies.

The mucosal maltase enzymes are characterized by an activity that produces glucose from linear glucose polymers, assayed with the disaccharide maltose. The related enzyme isomaltase produces glucose from branched glucose polymers, assayed with palatinose. Maltase and isomaltase activities are part of the 4 disaccharidases assayed from clinical duodenal biopsy homogenates. The reported maltase activities are more difficult to interpret than lactase or sucrase activities because both the sucrase-isomaltase and maltase-glucoamylase proteins have overlapping maltase activities. The early work of Dahlqvist identified 4 maltase activities from human small intestinal mucosa. On one peptide, sucrase (maltase Ib) and isomaltase (maltase Ia) activities shared maltase activities but identified the enzymes as sucrase-isomaltase. On the other peptide, no distinguishing characteristics of the 2 maltase activities (maltases II and III) were detected and the activities identified as maltase-glucoamylase. The nutritional/clinical importance of small intestinal maltase and isomaltase activities are due to their crucial role in the digestion of food starches to absorbable free glucose. This review focuses on the interpretation of biopsy maltase activities in the context of reported lactase, sucrase, maltase, and palatinase biopsy assay activity patterns. We present a classification of mucosal maltase deficiencies and novel primary maltase deficiency (Ib, II, III) and provide a clarification of the role of maltase activity assayed from clinically obtained duodenal biopsies, as a path toward future clinical and molecular genomic investigations.

Alpha amylase and Alpha glucosidase inhibitory effects of aqueous stem extract of Salacia oblonga and its GC-MS analysis

ABSTRACT Our present investigation deals with the phytochemical screening, estimation of total flavonoids, terpenoids and tannin contents to evaluate the anti-diabetic activities of Salacia oblonga stem followed by GC-MS analysis. It explores the natural compounds and the potential α-amylase and α-glucosidase inhibitory actions of stem extracts. The aqueous stem extract was selected from other extracts (ethanol, acetone, petroleum ether and chloroform) for the in vitro study of anti-diabetic activity by alpha amylase and alpha glucosidase inhibitory assays. The stem extract was also analyzed by gas chromatography mass spectrometry to identify the natural chemical components. Phytochemical analysis of aqueous stem extract showed major classes of secondary metabolites such as phenols, flavonoids, alkaloids, terpenoids, tannins, saponins. The total flavonoid, terpenoid, and tannin contents were quantified as 19.82±0.06 mg QE/g, 96.2±0.20 mg/g and 11.25±0.03 mg TAE/g respectively. The percentage inhibition of assays showed maximum inhibitory effects (59.46±0.04% and 68.51±0.01%) at a concentration of 100 mg/mL. The IC50 values of stem extract was found to be 73.56 mg/mL and 80.90 mg/mL for alpha amylase and alpha glucosidase inhibition. Fifteen chemical constituents were found by GC-MS analysis. This study suggest the aqueous stem extract of Salacia oblonga might be considered as potential source of bio active constituents with excellent antidiabetic activity.

C-geranylated flavanones from YingDe black tea and their antioxidant and α-glucosidase inhibition activities.

YingDe black tea is produced from crude tea prepared from leaves of Camellia sinensis var. assamica. In this work, we isolated and identified five novel flavanones, namely, amelliaone A-E (1-5), along with seven known compounds 6-12 from the ethanol extract of YingDe black tea. The structures of these five novel phenolic compounds were determined using extensive 1D and 2D nuclear magnetic resonance spectroscopy experiments. The compounds were further evaluated for antioxidant, α-glucosidase inhibitory, and cytotoxic activities. Compound 1 exhibited higher α-glucosidase inhibitory activity with a half-maximum inhibitory concentration value (IC50) of 10.2µM compared with acarbose (18.2µM).

Low concentration of sodium bicarbonate improves the bioactive compound levels and antioxidant and α-glucosidase inhibitory activities of tartary buckwheat sprouts.

This study aimed to investigate the effects of different concentrations of sodium bicarbonate (NaHCO3) on the accumulation of flavonoids, total phenolics and d-chiro-inositol (DCI), as well as the antioxidant and α-glucosidase inhibitory activities, in tartary buckwheat sprouts. Treatment with low concentrations of NaHCO3 (0.05, 0.1, and 0.2%) resulted in an increase in flavonoids, total phenolic compounds and DCI concentrations, and improved DPPH radical-scavenging and α-glucosidase inhibition activities compared with the control (0%). The highest levels of total flavonoids (26.69mg/g DW), individual flavonoids (rutin, isoquercitrin, quercetin, and kaempferol), total phenolic compounds (29.31mg/g DW), DCI (12.56mg/g DW), as well as antioxidant and α-glucosidase inhibition activities, were observed in tartary buckwheat sprouts treated with 0.05% NaHCO3 for 96h. These results indicated that appropriate treatment with NaHCO3 could improve the healthy benefits of tartary buckwheat sprouts.

Identification of phenolic antioxidants and bioactives of pomegranate seeds following juice extraction using HPLC-DAD-ESI-MSn.

Phenolics from free and hydrolyzed fractions of pomegranate juice (PJ) and seeds (PS) were evaluated. In general, total phenolic contents and scavenging of ABTS+, DPPH and hydroxyl radicals, as well as metal chelation of the soluble fraction from PS, were higher than those for PJ. Insoluble-bound phenolics from PS accounted for up to 27% of total scavenging capacity (free+esterified+insoluble-bound). Phenolic acids (13), monomeric flavonoids (8), hydrolysable tannins (12), proanthocyanidin (1) and anthocyanins (12) were tentatively characterized using HPLC-DAD-ESI-MSn. Several compounds were identified for the first time in PJ or PS. The inhibition of DNA damage (induced by hydroxyl and peroxyl radicals), copper-induced LDL-cholesterol peroxidation, as well as alpha-glucosidase and lipase activities were demonstrated, therefore supporting the potential exploitation of PJ and PS as sources of bioactive compounds.

Antioxidants and α-glucosidase inhibitors from Ipomoea batatas leaves identified by bioassay-guided approach and structure-activity relationships.

Sweet potato (Ipomoea batatas) leaf (SPL) is an underused commercial vegetable with considerable bio-activities. By means of DPPH scavenging ability and α-glucosidase inhibitory oriented isolation, 9 and 7 compounds were isolated and identified, respectively. Among them, trans-N-(p-coumaroyl)tyramine (1), trans-N-feruloyltyramine (2), cis-N-feruloyltyramine (3), 4,5-feruloylcourmaoylquinic acid (8), caffeic acid ethyl ester (10), 7-hydroxy-5-methoxycoumarin (11), 7,3'-dimethylquercetin (13) and indole-3-carboxaldehyde (15), were firstly identified from SPL, and four of them (1, 2, 3 and 10) were firstly identified from genus Ipomoea. Phenethyl cinnamides and 3,4,5-triCQA exhibited the strongest α-glucosidase inhibition, while 3,4,5-triCQA and diCQAs were the dominant antioxidants. Structure-activity relationship revealed that higher caffeoylation of quinic acid and lower methoxylation of flavonols resulted in stronger antioxidant activity, and methylation and cis-configuration structure of phenethyl cinnamides weaken the α-glucosidase inhibition. Aforementioned results could help to explain the antioxidant activity and anti-diabetic activity of SPL, and provide theoretical basis for its further application.

Norsesquiterpenoids and triterpenoids from strawberry cv. Falandi.

Falandi is a common strawberry (Fragaria × ananassa Duch.) cultivar in southern China. Further study of the chemical constituents in Falandi fruit led to the isolation of nine norsesquiterpenoids and three triterpenoids. Falandioside D (1) and falandins A (2) and B (3) were new norsesquiterpenoids, and the others excluding tormentic acid (11) were found in strawberry for the first time. Compounds 1 and 11 exhibited potent α-glucosidase inhibitory activity with the half maximal inhibitory concentration (IC50) values of 565.0 and 27.4 µM in comparison to acarbose (619.9 µM). Compounds 3, 7 (blumenol C glucoside), and 11 showed cytotoxicity against human nasopharyngeal carcinoma cell line CNE1 with the IC50 values of 57.6, 56.4, and 36.0 µM, respectively. Among new compounds, 1 showed 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging capacity (IC50=36.2 µM). These results suggested that non-phenolic constituents were also involved in the antidiabetic, antitumour, and antioxidant effects of strawberry fruit.

Bound Phenolics of Quinoa Seeds Released by Acid, Alkaline, and Enzymatic Treatments and Their Antioxidant and α-Glucosidase and Pancreatic Lipase Inhibitory Effects.

Unextractable phenolics from plant foods and their role in health benefits have become increasingly important. Meal residues of three quinoa seeds free of fat and extractable phenolics were subjected to acid, alkaline, and enzymatic hydrolyses. The total and individual phenolic compounds released were analyzed, and 19 phenolics, predominantly phenolic acids and several flavonoids, were identified. The concentration of bound phenolics was highest in black quinoa followed by red and white, regardless of the hydrolysis method. Higher phenolic contents also showed stronger antioxidant activities and inhibition of α-glucosidase and pancreatic lipase activities. Carbohydrases, that is, pectinase, xylanase and feruloyl esterase, which effectively liberated bound phenolics are known to be secreted by colonic bacteria, suggesting potential antioxidant and anti-inflammatory effects by these compounds in the large intestine during colonic fermentation. These results can also be applied to treat foods high in bound phenolics to enhance bioaccessibility.

Phenolics from strawberry cv. Falandi and their antioxidant and α-glucosidase inhibitory activities.

Three new phenolic glucosides, falandiosides A (1), B (2), and C (6) were isolated from strawberry (Fragaria×ananassa Duch.) cv. Falandi fruit, together with three flavone glucuronides (3-5), eleven lignan glycosides (12-22), and five others. Their structures were determined by spectroscopic methods. All the known phenolics were reported from strawberry for the first time. They were evaluated for antioxidant and α-glucosidase inhibitory activities. Three new and fifteen known phenolics showed potent 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity with IC50 values of 22.50-4.28µM in comparison to l-ascorbic acid (14.21µM). Quercetin 3-(6-methylglucuronide) (4), (+)-isolariciresinol 9'-glucoside (12), and (-)-isolariciresinol 9'-glucoside (13) were active in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Moreover, compounds 12 and 13 had moderate ferric reducing antioxidant power (FRAP) values. Further, two new and seven known phenolics exhibited more potent α-glucosidase inhibitory activity with IC50 values of 537.43-25.39µM than acarbose (619.94µM).

Phenolic profiles of 20 Canadian lentil cultivars and their contribution to antioxidant activity and inhibitory effects on α-glucosidase and pancreatic lipase.

Phenolic extracts from 20 Canadian lentil cultivars (Lens culinaris) were evaluated for total phenolic contents and composition, antioxidant activities (DPPH, FRAP, ORAC), and inhibitory properties against α-glucosidase and pancreatic lipase. Twenty one phenolic compounds were identified in the present study, with the majority being flavonoids, including kaempeferol glycosides, catechin/epicatechin glucosides and procyanidins. These phenolic compounds not only contributed significantly to the antioxidant activities, but they were also good inhibitors of α-glucosidase and lipase, two enzymes, respectively, associated with glucose and lipid digestion in the human intestine, thus contributing significantly to the control of blood glucose levels and obesity. More interestingly, it was the flavonols, not the flavanols, which showed the inhibitory activities against α-glucosidase and pancreatic lipase. Our result provides supporting information for developing lentil cultivars and functional foods with improved health benefits and suggests a potential role of lentil consumption in managing weight and control of blood glucose.

Cysteine-rich secretory protein 1 in seminal plasma: potential biomarker for the distinction between obstructive and nonobstructive azoospermia.

OBJECTIVE: To investigate the presence of cysteine-rich secretory protein 1 (CRISP1) in seminal plasma as a means of distinguishing between obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). DESIGN: Seminal plasma from normospermic donors (n = 45) and azoospermic donors (n = 80) was examined to determine CRISP1 levels. Neutral alpha-glucosidase (NAG) enzymatic activity was measured for comparison with CRISP1 levels. SETTING: Research unit of an academic medical center. PATIENT(S): Normospermic and azoospermic donors from the clinical andrology laboratory of the centre hospitalier universitaire de Québec and from Mount Sinai Hospital. INTERVENTION(S): Seminal CRISP1 measurement by Western blot analysis. Neutral alpha-glucosidase activity was evaluated by a photometric method. MAIN OUTCOME MEASURE(S): Seminal plasma CRISP1 levels, NAG activity, cutoff value, sensitivity, and specificity. RESULT(S): All seminal plasma samples from normospermic and nonobstructive azoospermic donors were CRISP1 positive, whereas CRISP1 was absent or present at low levels in samples from patients with OA. A significant correlation between seminal CRISP1 levels and NAG activity was found in azoospermic semen samples. The cutoff point to distinguish between donors with NOA or OA was established at 0.655 (relative intensity). At this threshold, specificity was 85% and sensitivity was 92%. CONCLUSION(S): Seminal CRISP1 combined with NAG activity can potentially distinguish between OA and NOA.

Inhibition of dipeptidyl peptidase (DPP)-IV and α-glucosidase activities by pepsin-treated whey proteins.

Inhibitors of the enzymes dipeptidyl peptidase (DPP)-IV and α-glucosidase are two classes of pharmacotherapeutic agents used for the treatment of type 2 diabetes. In the present study, whey protein isolate (WPI), α-lactalbumin, ß-lactoglobulin, serum albumin, and lactoferrin hydrolysates obtained by peptic digestion were investigated for their potential to serve as natural sources of DPP-IV and α-glucosidase inhibitors. Although inhibition of DPP-IV activity was observed in all pepsin-treated whey proteins studied, the α-lactalbumin hydrolysate showed the greatest potency with an IC50 value of 0.036 mg/mL. Conversely, only WPI, ß-lactoglobulin, and α-lactalbumin hydrolysates displayed some inhibitory activity against α-glucosidase. This study suggests that peptides generated from whey proteins may have dual beneficial effects on glycemia regulation and could be used as functional food ingredients for the management of type 2 diabetes.

Influence of drying and cooking process on the phytochemical content, antioxidant and hypoglycaemic properties of two bell Capsicum annum L. cultivars.

The present study evaluates the influence of drying and cooking processes on the health properties of two bell Capsicum annuum L. cultivars Roggiano and Senise compared with fresh peppers. The content of phytochemicals decreased in the order fresh>dried>dried frying processes. HPLC analysis was applied to quantify five flavonoids from peppers. Apigenin was identified as main constituent. Its content was affected by drying and dried frying processes. The antioxidant activity was evaluated by DPPH, ABTS, ß-carotene bleaching test and Fe-chelating activity assay. A comparable radical scavenging activity was observed for both cultivars. Interestingly, frying process did not influenced this property. Roggiano peppers exhibited the highest antioxidant activity using ß-carotene bleaching test with IC(50) values of 38.1 and 24.9 µg/mL for total extract and n-hexane fraction, respectively. GC-MS analysis of lipophilic fraction revealed the presence of fatty acids and vitamin E as major components. In the inhibition of the carbohydrate-hydrolyzing enzymes fresh Senise peppers exerted the strongest activity against α-amylase with an IC(50) value of 55.3 µg/mL. Our results indicate that C. annuum cultivars Roggiano and Senise have an interestingly potential health benefits not influenced by processes that are used before consumption.