Hypoglycemic peptide-enriched hydrolysates of Corbicula fluminea and Chlorella sorokiniana possess synergistic hypoglycemic activity through inhibiting α-glucosidase and dipeptidyl peptidase-4 activity.

BACKGROUND: The prevalence of diabetes mellitus worldwide has increased in recent decades. Maintaining the level of blood glucose is the most basic and important issue for diabetics. This study aimed to investigate the hypoglycemic activity of a combination of hypoglycemic peptide-enriched hydrolysates of Corbicula fluminea (ACH) and Chlorella sorokiniana (PCH). RESULTS: Combined supplementation of ACH and PCH synergistically inhibited α-glucosidase and DPP4 activities in vitro. After 4 weeks of treatment with ACH and/or PCH, the plasma glucose concentration and insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), total cholesterol (TC) and triglyceride (TG) levels significantly decreased. The hypoglycemic peptides in ACH and PCH were purified and assayed for α-glucosidase and DPP4 activity. The hypoglycemic peptides in ACH and PCH effectively decreased α-glucosidase and DPP4 activities. In silico assays showed that these two peptide types have different docking poses, which determined their inhibitory effect against α-glucosidase and DPP4 activity. CONCLUSION: Combined treatment with hypoglycemic peptide-enriched ACH and PCH could modulate blood glucose by synergistically inhibiting α-glucosidase and DPP4 activities. © 2021 Society of Chemical Industry.

Comprehensive chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba.

Extensive pharmacological research has demonstrated that Clerodendranthi Spicati Herba has an obvious anti-hyperglycemic effect via α-glucosidase inhibitory activity. However, the anti-hyperglycemic active fraction and its metabolic behavior in vivo have not been elaborated clearly. In this study, ultra-high-performance liquid chromatography coupled to quadrupole time of flight tandem mass spectrometry with data filtering strategy, including mass defect screening, diagnostic product ions and neutral loss identification, was established for chemical and metabolic profiling of anti-hyperglycemic active fraction from Clerodendranthi Spicati Herba. A total of 28 methoxylated flavonoids and 61 diterpenoids were rapidly identified. Four main known methoxylated flavonoids were purified and unambiguously identified by nuclear magnetic resonance analysis. Thirty-one absorbed diterpenoids, 12 absorbed methoxylated flavonoids, and 56 methoxylated flavonoids metabolites were identified in rat plasma, urine, bile, and feces after oral administration of anti-hyperglycemic active fraction. The methoxylated flavonoids were predominantly metabolized by demethylation, sulfation, and glucuronidation. Glucuronidation metabolites found in bile and urine after demethylation were dominant metabolites. Diterpenoids were absorbed into the blood mainly in the form of prototypes and excreted through bile and urine. These results indicated that methoxylated flavonoids and diterpenoids were responsible for α-glucosidase inhibitory activity, which might provide novel drug candidates for the management of diabetes mellitus.

Polyphenol fingerprinting and hypoglycemic attributes of optimized Cycas circinalis leaf extracts.

BACKGROUND: Cycas circinalis leaves are used to treat diabetes mellitus in local medicinal systems without any scientifically proved information on their medicinal potential and phytochemicals. In this study, the total phenolic contents, total flavonoid contents, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and inhibitory effects on α-glucosidase and α-amylase were determined for optimized hydroethanolic leaf extracts. Secondary metabolites were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS/MS). In vivo studies on diabetic albino mice were also carried out to evaluate the impact of the most active extract on their blood glucose levels. RESULTS: The 60% ethanolic extract showed the highest extract yield (209.70 ± 0.20 g kg-1 ) and total phenolic (154.24 ± 3.28 mg gallic acid equivalent) and flavonoid (78.52 ± 1.65 mg rutin equivalent per gram dried extract) contents and exhibited the maximum DPPH scavenging activity (IC50 = 59.68 ± 2.82 µg mL-1 ). The IC50 values for inhibition of α-glucosidase (58.42 ± 2.22 µg mL-1 ) and α-amylase (74.11 ± 1.70 µg mL-1 ) were also significant for the 60% ethanolic extract. The untargeted UHPLC-QTOF-MS/MS-based metabolite profiling confirmed the presence of iridoid glucoside, gibberellin A4, O-ß-d-glucosyl-4-hydroxy-cinnamate, 3-methoxy-2-phyenyl-4H-furo[2,3-h]chromen-4-one, kaempferol, withaferin A, amentoflavone, quercitin-3-O-(6″-malonyl glucoside), ellagic acid, and gallic acid. Plant extract at a dose of 500 mg kg-1 body weight reduced the blood glucose level by a considerable extent and also improved the lipid profile of diabetic mice after a 28-day trial. CONCLUSION: The findings revealed the medicinal potential of C. circinalis leaves to treat diabetes mellitus and provided the nutraceutical leads for functional food development. © 2020 Society of Chemical Industry.

Efficacy and Safety of Miglitol- or Repaglinide-Based Combination Therapy with Alogliptin for Drug-Naïve Patients with Type 2 Diabetes: An Open-Label, Single-Center, Parallel, Randomized Controlled Pilot Study.

BACKGROUND: Combination therapy with an alpha-glucosidase inhibitor or glinide plus a dipeptidyl peptidase-4 inhibitor is thought to be effective for glycemic control because of its effects on postprandial hyperglycemia. However, no studies have directly compared these two combination therapies in relation to efficacy and safety. METHODS: Eighteen patients with type 2 diabetes were studied. All had diabetes not adequately controlled with diet and exercise therapy, an HbA1c level of ≥7.5%, and were not receiving any medication for diabetes. The patients were randomized to either miglitol- or repaglinide-based combination therapy with alogliptin. Patients received miglitol or repaglinide monotherapy for 3 months (the miglitol and repaglinide groups, respectively), after which alogliptin was added to each group as combination therapy for 3 months. A meal tolerance test (MTT) was performed before the start of treatment and at the end of monotherapy and combination therapy. RESULTS: During the study period, decreases in HbA1c and glycated albumin were significantly greater in the repaglinide group than in the miglitol group; however, there was no significant difference between treatment groups at the end of the study. At the end of monotherapy, insulin secretion relative to glucose elevation (ISG0-30: area under the curve of insulin from 0 to 30 min during MTT [AUC0-30 of IRI]/AUC0-30 of plasma glucose) was significantly higher only in the repaglinide group; ISG0-30 did not significantly increase in either group after the addition of alogliptin. CONCLUSIONS: The addition of alogliptin to repaglinide monotherapy did not cause glucose-independent inappropriate insulin secretion and did not appear to increase the incidence of hypoglycemia.

An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications.

Recently the use of bioactive α-glucosidase inhibitors for the treatment of diabetes have been proven to be the most efficient remedy for controlling postprandial hyperglycemia and its detrimental physiological complications, especially in type 2 diabetes. The carbohydrate hydrolysing enzyme, α-glucosidase, is generally competitively inhibited by the α-glucosidase inhibitors and results in the delayed glucose absorption in small intestine, ultimately controlling the postprandial hyperglycemia. Here we have reviewed the most recent updates in the bioactive α-glucosidase inhibitors category. This review provides an overview of the α-glucosidase inhibitory potentials and efficiency of controlling postprandial hyperglycemia of various bioactive compounds such as flavonoids, phenolic compound, polysaccharide, betulinic acid, tannins, anthocyanins, steroids, polyol, polyphenols, galangin, procyanidins, hydroxyl-α-sanshool, hydroxyl-ß-sanshool, erythritol, ganomycin, caffeoylquinic acid, resin glycosides, saponins, avicularin, oleanolic acids, urasolic acid, ethanolic extracts etc., from various dietary and non-dietary naturally occurring sources.

Effects of hot­water extracts from 26 herbs on α­glucosidase activity.

α­glucosidase is a key enzyme that plays a role in glucose absorption in the gastrointestinal tract, and the inhibition of its activity induces the prevention of postprandial hyperglycemia. Several α­glucosidase inhibitors have been used as medicines for type 2 diabetes, but a similar effect is observed in natural resources, including traditional herbs and their phytochemicals. To identify the presence of the α­glucosidase inhibitory activity in herbs, in which various functional effects have been known to occur, the present study investigated the effects of hot­water extracts of 26 types of herbs on α­glucosidase activity in an in vitro assay. The results indicated significant increases in the inhibition of α­glucosidase activity in 1,000 µg/ml olive (P<0.01), white willow (P<0.01) and red rooibos hot­water extracts. Furthermore, ≥50% inhibition of α­glucosidase activity was determined to be significant in 1,000 µg/ml coltsfoot, green tea and bearberry hot­water extracts. In addition, the effects of bearberry, green tea and coltsfoot hot­water extracts on α­glucosidase activity in vivo were evaluated according to the blood glucose levels (BGLs) in maltose and glucose load model rats. It was indicated that the administration of these three herb extracts significantly reduced the increasing BGLs after maltose loading until 0.5 h compared with the control group. However, only coltsfoot extract significantly reduced the increasing BGLs after glucose loading until 0.5 h compared with the control group. Thus, the present results may facilitate the understanding of a novel functionality in traditional herbs, which could be useful for the prevention of disease onset and progression, such as in hyperglycemia and type 2 diabetes.

Dietary 5,6,7-Trihydroxy-flavonoid Aglycones and 1-Deoxynojirimycin Synergistically Inhibit the Recombinant Maltase-Glucoamylase Subunit of α-Glucosidase and Lower Postprandial Blood Glucose.

1-Deoxynojirimycin (1-DNJ) is the major effective component of mulberry leaves, exhibiting inhibitory activity against α-glucosidase. However, due to the low content of 1-DNJ in mulberry products, its level cannot meet the lowest dose to exhibit its activity. In this study, a combination of dietary 5,6,7-trihydroxy-flavonoid aglycones with 1-DNJ showed synergistic inhibitory activity against maltase of mice α-glucosidase and recombinant C- and N-termini of maltase-glucoamylase (MGAM) and baicalein with 1-DNJ exhibited the strongest synergistic effect. The synergistic effect of the combination was also confirmed by the maltose tolerance test in vivo. Enzyme kinetics, molecular docking, fluorescence spectrum, and circular dichroism spectrometry studies indicated that the major mechanism of the synergism is that baicalein was a positive allosteric inhibitor and bound to the noncompetitive site of MGAM, causing an increase of the binding affinity of 1-DNJ to MGAM. Our results might provide a theoretical basis for the design of dietary supplements containing mulberry products.

Antihyperglycemic Effects of Annona diversifolia Safford and Its Acyclic Terpenoids: α-Glucosidase and Selective SGLT1 Inhibitiors.

Annona diversifolia Safford and two acyclic terpenoids were evaluated to determine their antihyperglycemic activity as potential α-glucosidase and selective SGLT-1 inhibitiors. Ethanolic extract (EEAd), chloroformic (CHCl3Fr), ethyl acetate (EtOAcFr), aqueous residual (AcRFr), secondary 5 (Fr5) fractions, farnesal (1), and farnesol (2) were evaluated on normoglycemic and streptozocin-induced diabetic mice. EEAd, CHCl3Fr, Fr5, (1) and (2) showed antihyperglycemic activity. The potential as α-glucosidase inhibitors of products was evaluated with oral sucrose and lactose tolerance (OSTT and OLTT, respectively) and intestinal sucrose hydrolysis (ISH) tests; the potential as SGLT-1 inhibitors was evaluated using oral glucose tolerance (OGTT), intestinal glucose absorption (IGA), and urinary glucose excretion (UGE) tests. In OSTT and OLTT, all treatments showed significant activity at two and four hours. In ISH, half maximal effective concentrations (CE50) of 565, 662 and 590 µg/mL, 682 and 802 µM were calculated, respectively. In OGTT, all treatments showed significant activity at two hours. In IGA, CE50 values of 1059, 783 and 539 µg/mL, 1211 and 327 µM were calculated, respectively. In UGE Fr5, (1) and (2) showed significant reduction of the glucose excreted compared with canagliflozin. These results suggest that the antihyperglycemic activity is mediated by α-glucosidase and selective SGLT-1 inhibition.

In Vitro and In Vivo Medicinal Value of Culinary-Medicinal Lung Oyster Mushroom Pleurotus pulmonarius var. stechangii (Agaricomycetes).

Pleurotus pulmonarius var. stechangii is a culinary-medicinal mushroom commonly cultivated in subtropical countries in Asia. In this study, the in vitro antixanthine oxidase, antihyperglycemic, and in vivo anti-inflammatory activities of a methanol extract (ME) of P. pulmonarius var. stechangii fruiting bodies were evaluated. The xanthine oxidase inhibitory activity of the ME of P. pulmonarius var. stechangii was lower than that of allopurinol, a xanthine oxidase inhibitor used as a positive control. Eleven phenolic compounds were identified from the fruiting bodies of P. pulmonarius var. stechangii by HPLC analysis. The inhibitory effects of ME on α-amylase and α-glucosidase were moderate and lower than that of acarbose, a positive control. The ME inhibited the production of nitric oxide (NO) and nitric oxide synthases (iNOS) protein expression in lipopolysaccharide-induced RAW 264.7 macrophages. It also exhibited an inhibitory effect on carrageenan-induced hind paw edema in a rat model. Taken together, our experimental results demonstrated that the fruiting bodies of P. pulmonarius var. stechangii might be a good natural source to promote human health through its antixanthine oxidase, antihyperglycemia, and anti-inflammatory activities.

Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects.

Milk proteins have been hypothesized to protect against type 2 diabetes (T2DM) by beneficially modulating glycemic response, predominantly in the postprandial status. This potential is, amongst others, attributed to the high content of whey proteins, which are commonly a product of cheese production. However, native whey has received substantial attention due to its higher leucine content, and its postprandial glycemic effect has not been assessed thus far in prediabetes. In the present study, the impact of a milk protein hydrolysate of native whey origin with alpha-glucosidase inhibiting properties was determined in prediabetics in a randomized, cross-over trial. Subjects received a single dose of placebo or low- or high-dosed milk protein hydrolysate prior to a challenge meal high in carbohydrates. Concentration-time curves of glucose and insulin were assessed. Incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by low-dosed milk peptides compared to placebo (p = 0.0472), and a minor insulinotropic effect was seen. A longer intervention period with the low-dosed product did not strengthen glucose response but significantly reduced HbA1c values (p = 0.0244). In conclusion, the current milk protein hydrolysate of native whey origin has the potential to modulate postprandial hyperglycemia and hence may contribute in reducing the future risk of developing T2DM.

Identification of α-glucosidase inhibitors from cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking.

Leaves of Cyclocarya paliurus (CP) have a potential antihyperglycemic effect, but its active compositions responsible for the beneficial properties remain unclear. The CP extract exhibited remarkable α-glucosidase inhibitory activity with an IC50 value of 31.5 ± 1.05 µg mL-1, much lower than that of the positive control acarbose (IC50 = 296.6 ± 1.06 µg mL-1). To identify the specific α-glucosidase inhibitors from the CP extract, affinity ultrafiltration coupled with ultra-performance liquid chromatography and quadrupole-time-of-flight mass spectrometry (UF-UPLC-Q/TOF-MS/MS) was developed and 11 potential α-glucosidase inhibitors from CP extract were identified. In vitro α-glucosidase inhibitory assay verified that quercetin-3-O-glucuronide, kaempferol-3-O-rhamnoside, quercetin, kaempferol, asiatic acid and genistein were primarily responsible for the α-glucosidase inhibitory activity of the CP extract. Further, a hypoglycemia test also verified that these α-glucosidase inhibitors had the potential to reduce post-prandial hyperglycaemia in C57BL/6 mice. Moreover, the molecular docking study revealed that these identified α-glucosidase inhibitors more easily occupy the active sites of α-glucosidase than does the positive control acarbose. These findings suggest the CP tea leaves are the potential source of a hypoglycaemic agent.

Resveratroloside Alleviates Postprandial Hyperglycemia in Diabetic Mice by Competitively Inhibiting α-Glucosidase.

The regulation of postprandial blood glucose (PBG) levels is an effective therapeutic method to treat diabetes and prevent diabetes-related complications. Resveratroloside is a monoglucosylated form of stilbene that is present in red wine, grapes, and several traditional medicinal plants. In our study, the effect of resveratroloside on reducing PBG was studied in vitro and in vivo. In comparison to the starch treatment alone, the oral administration of resveratroloside-starch complexes significantly inhibited the PBG increase in a dose-dependent pattern in normal and diabetic mice. The PBG level treated with resveratrol (30 mg/kg) was not lower than that of resveratroloside. Further analyses demonstrated that resveratroloside strongly and effectively inhibited α-glucosidase, with an 50% inhibitory concentration value of 22.9 ± 0.17 µM, and its inhibition was significantly stronger than those of acarbose and resveratrol (264 ± 3.27 and 108 ± 2.13 µM). Moreover, a competitive inhibition mechanism of resveratroloside on α-glucosidase was determined by enzyme kinetic assays and molecular docking experiments. The molecular docking of resveratroloside with α-glucosidase demostrated the competitive inhibitory effect of resveratroloside, which occupies the catalytic site and forms strong hydrogen bonds with the residues of α-glucosidase. Resveratrol was also determined to be a competitive inhibition mechanism on α-glucosidase by enzyme kinetic assays and molecular docking experiments. This study suggested that resveratroloside had the ability to regulate PBG levels and can be considered a potential agent for the treatment of diabetes mellitus.

Active Components, Antioxidant, Inhibition on Metabolic Syndrome Related Enzymes, and Monthly Variations in Mature Leaf Hawk Tea.

Hawk tea is a rich and edible resource, traditionally used as a beverage in South China. This drink has many pharmacologic effects, such as acting as an antioxidant and reducing blood sugar and lipids. The objective of this work was to explore the active compound contents, bioactivities and their monthly changes, and optimize the harvest time. In the present study, Hawk tea from each month in 2017 was collected and extracted with 70% (v/v) ethanol. The contents of the total flavonoids and total phenols were determined using the colorimetric method. We determined the contents of seven characteristic active substances-hyperin, isoquercitrin, trifolin, quercitrin, astragalin, quercetin, and kaempferol-using high-performance liquid chromatography. The crude extract was tested for its antioxidant and inhibitory properties on enzymes involved in metabolic syndrome. Specifically, 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing power assay, and the inhibition capacity test on α-glucosidase and lipase were conducted to determine the antioxidant effect in vitro, as well as the reduction of blood sugar and lipids. Monthly variations in activities and components were determined by numeric analysis and comparison. Correlation analysis revealed that antioxidant effects are significantly correlated with the total flavonoids. The hierarchical cluster analysis of bioactivities and their contents indicates that October and November are the best harvesting months, which differs with the habitual collection of Hawk tea.

Voglibose-mediated alterations in neurometabolomic profiles in the hypothalamus of high-fat diet-fed mice.

The alpha-glucosidase inhibitor voglibose (VO) was recently reported to have a protective effect against weight gain as well as affect various metabolic changes related to food intake and gut-brain signaling. We hypothesized that VO prevents weight gain by altering neurometabolome profiles in the hypothalamus to reduce food intake. To test this hypothesis, we assessed metabolite profiles in the hypothalamus of standard diet- or high-fat (HF) diet-fed mice in the absence or presence of VO. In total, 29 male C57BL/6 mice were divided into 3 groups: (1) lean control, (2) HF, and (3) HF + VO. Vehicle or VO was administered for 12 weeks. The results showed that there were alterations in levels of metabolites across several metabolic pathways in the hypothalamus. VO treatment increased levels of many amino acids including arginine, glutamine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in the hypothalamus. In addition, levels of 2-hydroxy-2-methyl-butyric acid in the hypothalamus were significantly increased after VO administration in HF diet-fed mice. Among lipid metabolites, levels of fatty acids were higher in the hypothalamus of VO-treated mice than in that of HF diet-fed mice. In terms of the energy status, the ATP/ADP ratio was higher in the hypothalamus of VO-treated mice (P < 0.001), thereby indicating an energy surplus. In conclusion, VO supplementation altered metabolite profiles in the hypothalamus to enhance catabolism, which is possibly responsible for the hypophagic effect of VO in HF diet-fed mice.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Antidiabetic activity, glucose uptake stimulation and α-glucosidase inhibitory effect of Chrysophyllum cainito L. stem bark extract.

BACKGROUND: Chrysophyllum cainito L., a tropical fruit tree, has been used as an alternative medicine for the treatment of diabetic patients in many countries. However, there is very limited scientific rationale for this medical use. The present study aimed to evaluate the antidiabetic activity of the extract from C. cainito stem bark and the possible mechanisms underlying this activity. METHODS: Phytochemistry and in vitro antioxidant capacity of the extract were studied. Hypoglycemic activity of the extract was examined in normal and alloxan-induced diabetic mice. The effect of C. cainito extract on glucose absorption and glucose uptake were conducted using mouse isolated jejunum and abdominal muscle, respectively. Finally, an in vitro effect of C. cainito extract on α-glucosidase activity was evaluated. RESULTS: C. cainito extract possessed a strong antioxidant activity comparable to the ascorbic acid and butylated hydroxytoluene. The extract at 500 mg/kg significantly reduced the area under curve of blood glucose level in oral glucose tolerance test in normal mice. In alloxan-induced diabetic model, similar to glibenclamide, a single dose of the extract significantly decreased fasting blood glucose level from 387.17 ± 29.84 mg/dl to 125.67 ± 62.09 mg/dl after 6 h of administration. From the isolated jejunum experiment, the extract at any doses used did not inhibit glucose absorption. However, the extract at 50 µg/ml significantly increased the amount of glucose uptake by abdominal muscles in the presence of insulin (P < 0.05). Lastly, it was found that the extract produced stronger inhibition of α-glucosidase activity (IC50 = 1.20 ± 0.09 µg/ml) than acarbose (IC50 = 198.17 ± 4.74 µg/ml). CONCLUSION: Direct evidence of antidiabetic activity of C. cainito stem bark with possible modes of action, glucose uptake stimulation and α-glucosidase inhibitory effect, was reported for the first time herein. These data support the potential use of this plant for the treatment of diabetic patients.

Microencapsulation and the Characterization of Polyherbal Formulation (PHF) Rich in Natural Polyphenolic Compounds.

Microencapsulation of polyherbal formulation (PHF) extract was carried out by freeze drying method, by employing gum arabic (GA), gelatin (GE), and maltodextrin (MD) with their designated different combinations as encapsulating wall materials. Antioxidant components (i.e., total phenolic contents (TPC), total flavonoids contents (TFC), and total condensed tannins (TCT)), antioxidant activity (i.e., DPPH, β-carotene & ABTS⁺ assays), moisture contents, water activity (aw), solubility, hygroscopicity, glass transition temperature (Tg), particle size, morphology, in vitroα-amylase and α-glucosidase inhibition and bioavailability ratios of the powders were investigated. Amongst all encapsulated products, TB (5% GA & 5% MD) and TC (10% GA) have proven to be the best treatments with respect to the highest preservation of antioxidant components. These treatments also exhibited higher antioxidant potential by DPPH and β-carotene assays and noteworthy for an ABTS⁺ assays. Moreover, the aforesaid treatments also demonstrated lower moisture content, aw, particle size and higher solubility, hygroscopicity and glass transition temperature (Tg). All freeze dried samples showed irregular (asymmetrical) microcrystalline structures. Furthermore, TB and TC also illustrated the highest in vitro anti-diabetic potential due to great potency for inhibiting α-amylase and α-glucosidase activities. In the perspective of bioavailability, TA, TB and TC demonstrated the excellent bioavailability ratios (%). Furthermore, the photochemical profiling of ethanolic extract of PHF was also revealed to find out the bioactive compounds.

Zanthoxylum armatum DC extracts from fruit, bark and leaf induce hypolipidemic and hypoglycemic effects in mice- in vivo and in vitro study.

BACKGROUND: Zanthoxylum armatum DC is an important medicinal plant of south East Asia, and has been used to treat various ailments in traditional medicine including diabetes. This study investigated the in vitro and in vivo antidiabetic and biochemical effects of extracts of Z. armatum in mice. METHOD: The extracts of fruit, bark and leaf from Z. armatum were tested for α-glucosidase inhibition activity. Albino mice of either sex weighing (26-30 g) assigned into groups. Diabetes was induced by IP injection of alloxan monohydrate (150 mg/kg). The extracts (500 mg/kg) and standard (Glibenclamide 10 mg/kg) were administered to mice for 15 days. Serum biochemical parameters were monitored for the period of study. RESULTS: The leaves and bark extracts showed maximum α-glucosidase inhibition (96.61 ± 2.13 and 93.58 ± 2.31% respectively). The extracts treated and the standard treated groups showed significant decrease in the fasting blood glucose levels compared to diabetic control. The effect was more pronounced in mice treated with leaves extract. In the in vivo studies body weights of diabetic mice treated with Z. armatum extracts and the standard did not reduced to extent as observed in diabetic control and this difference was significant (p < 0.05). There was a significance (p < 0.001) improvement in blood hemoglobin, urea, creatinine, cholesterol, and triglycerides of the extracts treated diabetic mice. The extracts showed hypolipidemic effect by reducing the LDL level. The extracts produced no prominent changes in proteins levels. CONCLUSION: It can be concluded that Z. armatum extracts showed excellent antidiabetic potential in vivo and in vitro and could be considered for further appraisal in clinical assessment and drug development.

Systematic study on metabolism and activity evaluation of Radix Scutellaria extract in rat plasma using UHPLC with quadrupole time-of-flight mass spectrometry and microdialysis intensity-fading mass spectrometry.

Radix Scutellaria is a widely used traditional Chinese medicine in the treatment of various diseases. However, the activities of the absorbed components and metabolites of its main flavones in rat plasma need further investigation. In this study, a systematic method based on ultra-high performance liquid chromatography with quadruple time-of-flight mass spectrometry was developed to speculate the absorbed components and metabolites of the main flavonoids in Radix Scutellaria extract in rat plasma sample after oral administration of the extract. Twelve compounds, including four prototype components and eight metabolites, were confirmed in drug-containing plasma. In these metabolites, five were originally detected in rat plasma. The possible metabolic pathways of these polyhydroxy flavones in vivo were described and clarified. Microdialysis with intensity-fading mass spectrometry was originally employed to investigate the binding affinities of the absorbed components and metabolites with α-glucosidase. The order of their binding affinities was P4 > P3 > P2 > P1≥M5 > M3 > M1. The research result is helpful to deepen the understanding of the absorbed components and metabolic pathways of main flavones from Radix Scutellaria, and provide a new approach to screen potential inhibitors from in vivo components originated from Chinese herb.

Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project.

We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.