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Cyclophellitol is a potent and selective mechanism‐based retaining β‐glucosidase inhibitor that has served as a versatile starting point for the development of activity‐based glycosidase probes (ABPs). We developed routes of synthesis of eight mono‐ and dideoxycyclophellitols and cyclophellitol aziridines, the latter as ABPs carrying either a biotin or fluorophore linked to the aziridine nitrogen. We reveal the potency of these 24 compounds as inhibitors of the three human retaining β‐glucosidases, GBA1, GBA2 and GBA3. We show that 3,6‐dideoxy‐β‐galacto‐cyclophellitol aziridine selectively captures GBA3 over GBA1 and GBA2 in extracts of cells overexpressing both GBA2 and GBA3. We also identify a probe that selectively labels GBA1 and GBA2 over GBA3 at lower concentrations. In sum, the here‐presented studies reveal new chemistries to prepare chiral, substituted cyclitol epoxides and aziridines, add to the growing suite of cyclophellitols varying in configuration and substitution pattern, and yielded a reagent that may find use to investigate the physiological role and therapeutic relevance of the most elusive of the three retaining β‐glucosidases: GBA3. [ABSTRACT FROM AUTHOR]

Lemongrass (genus Cymbopogon) is commonly used in foods, beverages, cosmetics, pharmaceuticals, and material science. Cymbopogon ambiguus A. Camus, the Australian Native Lemongrass, is a lesser-known member of the genus Cymbopogon, and research on this plant is scarce. Australian Indigenous people use the stalks and leaves of C. ambiguus as teas. Dried chopped leaves are also used as herbs in cooking. The aim of this study was to determine the proximate composition and bioactive properties of Australian native lemongrass (C. ambiguus). Antimicrobial capacity was carried out using the well diffusion method, antioxidant capacity by the FRAP method, and antidiabetic capacity by using the α-glucosidase inhibitory activity assay. The results obtained in the current study were compared with previously published literature on lemongrass (C. citratus). The results showed that C. ambiguus has lower fat and protein content and lower antioxidant and antimicrobial capacities than C. citratus, but it is very rich in fibre (67.55%) and has strong α-glucosidase inhibitory capacity. The total phenolic and total flavonoid content determined in the aqueous extract of C. ambiguus are also notable. The results of the present study showed that Australian native lemongrass has promising bioactive potential to be used as an alternative native herbal tea. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14 µM), with IC50 values ranging from 1.13 to 28.27µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06 µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM). [ABSTRACT FROM AUTHOR]

Vernonia amygdalina L., commonly utilized in traditional Vietnamese folk medicine for the management of afflictions including liver diseases, hypertension, diabetes, and elevated cholesterol levels. Despite its extensive employment in local herbal remedies, there exists a scarcity of scientific investigations elucidating its pharmacological and therapeutic potential. This research investigated the antioxidant activity of leaf extracts using a range of solvents, including n-hexane, chloroform, ethyl acetate, n-butanol, ethanol, and water. The ethyl acetate extract was identified as the most potent antioxidant, exhibiting EC50 values of 8.42 and 71.88 µg/mL in ferric reduction and DPPH assays, respectively. The hepatoprotective activity, as measured using the cellular lipid peroxidation method of ethanol leaf extract (IC50 = 5.87 µg/mL) is 4.75 times stronger than the trolox. Additionally, the ethanol extract demonstrated significant inhibitory potential against α-amylase and α-glucosidase enzymes (IC50 of 480.00 and 72.53 µg/mL, respectively). The acute oral toxicity study conducted on a mouse model indicates a safety margin at the experimental dose Dmax = 18.44 g extract/kg. Additionally, this study encompassed a leaf microdissection of V. amygdalina, elucidating pivotal morphological features. So, it is safe for further studies and producing functional products for disease prevention. [ABSTRACT FROM AUTHOR]

Ethnobotanically in Indonesia, Diospyros celebica Bakh is recognized as having antidiabetic activity. This study aimed to isolate antidiabetic compounds from the leaves of Eboni (Diospyros celebica). D. celebica leaves were dried and extracted with 96% ethanol, then fractionated and purified guided by antioxidant activity test, a-glucosidase inhibitory test, and dipeptidyl peptidase-4 (DPP-4) inhibitory test until bioactive isolates were obtained. The isolates were identified and their structures were determined based on NMR 1H, 13C, 2D, and LCMS/MS spectroscopic data. Extracts and fractions have potential antioxidant (DPPH), glucosidase inhibitor, and DPP-4 inhibitor activities as well as containing flavonoids and polyphenols. From the ethyl acetate fraction, isolate 26a-2 namely 3,5-digalloyl-(-)- epiafzelechin was obtained which was active as a DPPH scavenger, glucosidase inhibitor, and DPP4 inhibitor. The extracts, fractions, and flavonoid compounds in D. celebica leaves have the potential for antidiabetic drug candidates. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a metabolic dreadful disease caused by an uncontrolled glucose level in the bloodstream, particularly high after a meal. Inhibitors of glucosidases, involved in the digestion of carbohydrates, can regulate this post‐prandial increase in glucose concentration. The traditional drugs act as competitive inhibitors of both pancreatic α‐amylase and α‐glucosidases and this unselective inhibition is behind severe gastrointestinal side effects related to the concomitant inhibition of α‐amylase. We described herein some perglycosylated cyclodextrins as efficient and selective inhibitors of α‐glucosidase with low micromolar IC50 (3.64‐7.98 μM) compared to the acarbose (IC50 212 μM), clinically used for patients suffering from type 2 diabetes. On the other hand, they do not inhibit α‐amylase (IC50>500 μM). Structure/activity relationship rationalization suggests multiple interactions between the described inhibitors and α‐glucosidase, which support the existence of both active site and allosteric interactions. [ABSTRACT FROM AUTHOR]

Objective: Preclinical studies suggest that thiazolidinediones (TZDs) may have a protective effect on rheumatoid arthritis (RA), but evidence from population‐based studies is scarce. This study aimed to assess the association between use of TZDs and incidence of RA in a retrospective cohort of patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort of patients with T2DM who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled. We applied the inverse probability of treatment weighted Cox model to estimate the hazard ratio (HR) of RA incidence associated with the use of TZDs compared with AGIs. Results: The final analysis included 56,796 new users of AGIs and 14,892 new users of TZDs. The incidence of RA was 187.4 and 135.2 per 100,000 person‐years in AGI users and TZD users, respectively. Compared with use of AGIs, TZD use was associated with a reduction in RA incidence, with an HR of 0.72 (95% confidence interval [95% CI] 0.59–0.89). HRs for cumulative use of TZDs for 0.51 to 4.0 years and more than 4 years with incidence of RA were 0.55 (95% CI 0.35–0.88) and 0.74 (95% CI 0.57–0.98), respectively. Various subgroup analyses and sensitivity analyses were consistent with the primary analysis. Conclusion: Use of TZDs is associated with a decreased risk of incident RA in patients with T2DM. [ABSTRACT FROM AUTHOR]

Gardenia is a genus of about 140 different plant species of the Rubiaceae family. Previous studies have shown that terpenes and phenolics extracted from Gardenia sp. showed numerous potential bioactivities. In this study, the chemical constituents of G. angkorensis, their cytotoxic and αglucosidase inhibition activities were investigated. The phytochemical investigation of the dichloromethane extract of G. angkorensis leaves growing in Vietnam has led to the isolation of 19α-hydroxyoleanolic acid 3-Ο-β-D-glucuronopyranoside (1), chikusetsusaponin IVa, 3 β, 16 β, 21 β, 23, 24-pentahydroxy urs-12,18,20-trien-28-oic acid-γ-lactone (3), linalool glucoside and linalyl 6-O-α-L-arabinopyranosyl-β-D-glucopyranoside (5). The identities of the compounds were based on the analysis of their NMR data. Compound 1 showed moderate inhibition against αglucosidase with IC50 value of 58.01 ± 4.45 µM while compounds 3 (IC50 186.60 ± 4.68 µM) and 5 (IC50 239.53 ± 7.22 µM) exhibited weak cytotoxicity against the KB cell line and Hep G2 cell line (IC50 values 180.80 ± 7.16 µM, 253.95 ± 8.14 µM). [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is one of the chronic non-communicable diseases and has been rapidly increasing globally. Alpha glucosidase is an important enzyme that hydrolyzes polysaccharides into monosaccharides before being absorbed into the bloodstream. The alpha glucosidase inhibitors, such as acarbose are expensive and have several adverse effects. The use of herbal products to prevent or treatment of disease is becoming popular. There are many herbal products that can reduce blood sugar levels. However, taking herbal products with anti-DM medicines may cause herb-drug interactions that affect either the pharmacokinetics or pharmacodynamics of the drugs, leading to adverse effects or ineffective treatment. The aim of this study is to examine the effect of herbal extracts on alpha-glucosidase activity and the level of cytochrome P450 3A4 (CYP3A4) by using HepaRG as a model. Three herbs that reported blood glucose-lowering activity were selected including Moringa oleifera, Momordica charantia, and Morus alba. All herbs were extracted with 95% ethanol and tested for their in vitro alpha glucosidase inhibitory activity. The results showed that M. alba extract exhibits the highest activity (IC50= 83.75 µg/mL). Then, the extracts were evaluated for their cytotoxicity on the HepaRG cell line. All extracts showed no cytotoxicity at concentrations up to 250 µg/mL. The sub-cytotoxic concentration of each extract was selected to test for the effect on the CYP3A4 enzyme. The results showed that only M. alba extract elevated the level of CYP3A4, while the others slightly reduce the level of CYP3A4. However, this is a preliminary study that the major compounds of each extract must be isolated and evaluated in the future. [ABSTRACT FROM AUTHOR]

Cellular stress, notably oxidative, inflammatory, and endoplasmic reticulum (ER) stress, is implicated in the pathogenesis of cardiovascular disease. Modifiable risk factors for cardiovascular disease such as diabetes, hypercholesterolemia, saturated fat consumption, hypertension, and cigarette smoking cause ER stress whereas currently known cardioprotective drugs with diverse pharmacodynamics share a common pleiotropic effect of reducing ER stress. Selective targeting of oxidative stress with known antioxidative vitamins has been ineffective in reducing cardiovascular risk. This "antioxidant paradox" is partially attributed to the unexpected aggravation of ER stress by the antioxidative agents used. In contrast, some of the contemporary antihyperglycemic drugs inhibit both oxidative stress and ER stress in human coronary artery endothelial cells. Unlike sulfonylureas, meglitinides, α glucosidase inhibitors, and thiazolidinediones, metformin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors are the only antihyperglycemic drugs that reduce ER stress caused by pharmacological agents (tunicamycin) or hyperglycemic conditions. Clinical trials with selective ER stress modifiers are needed to test the suitability of ER stress as a therapeutic target for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a serious, long-term disease when the pancreas doesn't make enough insulin or when the body can't use the insulin it makes well. Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by elevated blood glucose levels due to insulin resistance and impaired secretion, primarily due to inefficient intestine glucose absorption through the a-glucosidase enzyme. Long-term synthetic drug use can cause issues in the digestive system, kidneys, and liver. Alternative treatments that use herbal products include the ashitaba (Angelica keiskei Koidzumi) plant, which has been evaluated as an α-glucosidase inhibitor. The purpose of this study was to use molecular docking and virtual screening to identify potential α-glucosidase inhibitors from Ashitaba (Angelica keiskei Koidzumi) isolates using a ligand-based pharmacophore model. The screening methods used were ligand-based virtual screening, dockingbased virtual screening, and molecular docking. By using 8 training sets of ashitaba isolates, the best model was obtained with 18 features, including two aromatic ring bonds, nine hydrophobic bonds, three hydrogen bond donors, and four hydrogen bond acceptors. The pharmacophore model and docking-based virtual screening simulations of 270,547 molecules in the ZINC Natural Product database and further investigation using molecular docking yielded (R)-N-(diaminomethylene)-3-hydroxy-3-((S)-6-(4-(hydroxyamino)benzyl)-2-(2-hydroxypropan-2-yl)-4-methoxy-5-oxo-2,3-dihydro-5H-furo[3,2-g]chromen-7-yl)propan-1-aminium (ZINC000085594472), (R)-3-((S)-4-(cyclopentyloxy)-6-(4-(hydroxyamino)benzyl)-2-(2-hydroxypropan-2-yl)-5-oxo-2,3-dihydro-5H-furo[3,2-g]chromen-7-yl)-N-(diaminomethylene)-3-hydroxypropan-1-aminium (ZINC000085594416), and (S,E)-1-(1-(2-hydroxy-5-(7-(4-hydroxy-3-methoxyphenyl)-2-isopropyl-5-oxohept-3-en-1-yl)-3-((iminio(methylamino)methyl)amino)phenoxy)cyclopentyl)-N-methylmethanaminium (ZINC000085597046) as the three top hits with binding energies of -16.09, -15.83, and -15.76 kcal/mol, respectively. In conclusion, the (R)-N-(diaminomethylene)-3-hydroxy-3-((S)-6-(4-(hydroxyamino)benzyl)-2-(2-hydroxypropan-2-yl)-4-methoxy-5-oxo-2,3-dihydro-5H-furo[3,2-g]chromen-7-yl)propan-1-aminium (ZINC000085594472) was a more potential candidate for a-glucosidase inhibitor. [ABSTRACT FROM AUTHOR]

Caesalpinia sappan (CS) has been commonly used in beverage and folk medicine in China and ASEAN countries because of its various therapeutic properties. Only the heartwood has long been used in traditional medicines due to the presence of high concentration of brazilin (one of the most important bioactive compounds), whereas the other parts are limited in use. Thus, this work aimed to investigate ways of utilizing other parts of CS. This information is important for further use of other CS parts to promote zero waste and hence sustainable resource utilization. Herein, the crude ethanolic (CEE) and crude aqueous (CAE) extracts from twelve parts of CS were evaluated for their biological activities for the first time. Our work demonstrates that not only the heartwood, but also other parts of CS exhibit interesting biological activities. CAE from heartwood of branches exhibits the highest antioxidant activity, which is higher than that of the positive control, butylated hydroxytoluene. CEE from florets shows the highest inhibitory effect against α-amylase, while CAE of barks shows better α-glucosidase inhibitory activity than the existing glucosidase inhibitor (acarbose). Molecular docking of brazilin (key bioactive compound) to both α-amylase and glucosidase can also confirm the tight binding of brazilin to α-glucosidase. [ABSTRACT FROM AUTHOR]

Diabetes remains one of the health issues in Indonesia. The number of diabetes patients is increasing each year. The number of diabetes patients also impacts the use of diabetes medications, increasing the demand for diabetes drugs. Acarbose is commonly used to manage diabetes by inhibiting the α-glucosidase and α-amylase. However, acarbose has side effects such as diarrhea, abdominal bloating, and borborygmus. Therefore, an alternative with a similar mechanism to acarbose is needed. As reported that Java apple (Syzygium samarangense) has the potency to inhibit α-glucosidase and α-amylase. This study aimed to analyze the potency of the ethyl acetate extract of Java apple stem bark as an α-glucosidase and α-amylase inhibitor using an in silico approach. The types of α-glucosidase used are human maltase-glucoamylase (MGAM) and human pancreatic α-amylase (HPA) as α-amylase. From 61 compounds presented in S. samarangense ethyl acetate extract, 17 compounds showed good inhibition and docked at the same active site as acarbose (control drug), indicating that the compounds serve as α-glucosidase and α-amylase inhibitors. The binding affinity of these compounds ranges from -8.4 to -10.8 kcal/mol. Three compounds (epigallocatechin, isoengeletin, and kaempferol-3-O-rhamnoside) showed good drug-likeness and drug score value. The drug-likeness value is 0.31525, 1.8995, and 1.9289; the drug score value is 0.82, 0.79, and 0.77, respectively. The toxicity of these compounds was not detected. Therefore, epigallocatechin, isoengeletin, and kaempferol-3-O-rhamnoside are promising drug candidates. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic disorder which characterized by high concentration of blood glucose. It is known as one of the major deadly diseases that require a serious attention. Many conventional drugs which have been employing in treating the disease are reported to less effective, expensive and some are not locally available. Therefore, in order to search for more effective, inexpensive and locally available drug, this study investigated antidiabetic activity of Cu(II) complex of King of bitters leaves crude extract. The crude extract of the plant was obtained in n-hexane. The metal complex of the crude extract was synthesized and characterized using solubility tests, Infrared and Ultraviolet-Visible spectroscopic analyses. The antidiabetic activities of the crude extract and its metal complex were examined against α-amylase and α-glucosidase enzymes while acarbose drug was employed as a standard drug. The metal complex showed different degrees of solubility in different solvents. Infrared analysis suggested coordination of the crude extract to the metal ion through oxygen donor atom while the formation of the complex was affirmed through the occurrence of d-d transitions in the visible region of the metal complex. The crude extract and its metal complex displayed good activities against a-amylase and a-glucosidase enzymes. It is suggested that the compounds are promising candidates to inhibit a-amylase and a-glucosidase. [ABSTRACT FROM AUTHOR]

A series of new phenyl acetylene and isoxazole analogues of arjunolic acid were designed, synthesized and evaluated (3–8) for their tyrosinase and alpha glucosidase inhibitory potential. All the tested analogues exhibited stronger inhibitory activity than the standard drug or parent compound. Of these, compound (7) displayed the most potent tyrosinase inhibitory action with IC50 (14.3 ± 7.6) of about three folds more than the standard drug, kojic acid (41.5 ± 1.0). Further, compound (8) (14.5 ± 0.15) possessed the potent alpha glucosidase inhibitory action with IC50 value comparable to that of standard, acarbose (10.4 ± 0.06). Henceforth, compounds (7) and (8) are promising candidates for further studies. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) and dementia cause heavy health burden in mainland China, where few studies have investigated the association between glucose‐lowering agents and dementia risk. We aimed to assess the association between use of thiazolidinediones (TZDs) and dementia incidence in a mainland Chinese population with T2DM. Methods: A retrospective cohort of T2DM patients who were new users of TZDs or alpha glucosidase inhibitors (AGIs) was assembled using the Yinzhou Regional Health Care Database. A Cox model with inverse probability of treatment weighting (IPTW) for controlling potential founding was applied to estimate the hazard ratio (HR) of the association between use of TZDs and dementia risk. Results: A total of 49 823 new users of AGIs and 12 752 new users of TZDs were included in the final cohort. In the primary analysis, the incidence of dementia was 195.7 and 78.2 per 100 000 person‐years in users of AGIs and TZDs respectively. TZD use was associated with a reduced risk of incident dementia after adjusting for potential confounding using IPTW, with a HR of 0.51 (95% CI, 0.38–0.67). The results in various subgroup analyses and sensitivity analyses were consistent with the findings of the primary analysis. Conclusions: Use of TZDs is associated with a decreased risk of dementia incidence in a mainland Chinese population with T2DM. [ABSTRACT FROM AUTHOR]

The antioxidant content of Baper tea was determined using phytochemical testing, and the potential of these contents as immunomodulatory agents and candidates for standardized herbal medications was investigated. A randomized design was used in this experimental study. Phytochemical assays are used to determine the antioxidant content of Baper tea, whereas organoleptic studies are performed using hedonic tests. A literature review was used to assess the content's potential as an immunomodulatory agent and candidate for standardized herbal medicine. The study lasted four months at the Biology and National Food and Drug Agency Laboratory in Bali Province. Data analysis is based on descriptive methods. Baper tea is prepared in a 2.1.1 ratio. According to the hedonic test results, 41 panelists (87.23 %) prefer Baper tea products based on their color assessment, flavor, aroma, community reception, and acceptability. The matrix and security test revealed a water content of 4.43 %, an IC50 of 24.27 ppm, α-glucosidase inhibitors of 12.18 ppm, a total phenolic content of 28.00 %, and a total flavonoid content of 15.57 %. Baper tea raw materials contain components that have the potential to act as immunomodulatory agents and candidates for standardized herbal medications based on local wisdom. [ABSTRACT FROM AUTHOR]

The aim of the study is to screen the morphological, anatomical, biological, and chemical profiles of the leave extracts of endemic Polyscias species namely P. dichroostachya (PD), P. gracilis (PG), and P. mauritiana (PM) from Mauritius. The morphology and anatomy of the leaves were studied using a microscope. Phytochemical screening of extracts using LC-MS/MS was carried out by ionization in both positive and negative modes. The leaves are pinnately compound, hypostomatic, dorsiventral, with a prominent mid vein with secretion cavities, and they can be distinguished by their midrib shape and anatomy. From the molecular mass and fragmentation data, 31 terpenoid saponins, 19 flavonoids, 17 acids, 7 terpenes, and 10 miscellaneous compounds including pyrrolidines and acetylenes in different extracts (hexane, ethanol, and aqueous) were identified. Extracts from the three species using DPPH radical scavenging activity exhibited good to moderate antioxidant activities with IC50 values in the range of 2.1- 70.8 mg/ml and the ethanolic extract of PD showing the highest activity. Aqueous extracts of PG and PM potently inhibited alpha-glucosidase with IC50 values of 0.50 and 2.62 mg/ml. The different leaf extracts exhibited moderate activity against a panel of gram-positive and gram-negative bacteria. This is probably the first report on the extensive chemical profiling and morphology of these endemic Polysias spp. from Mauritius and the results indicate that these leaf extracts have beneficial health properties and are thus worth exploiting further. [ABSTRACT FROM AUTHOR]

Pleurotus ostreatus cv. Florida is one of the widely used edible mushroom. The polysaccharides from this mushrooms have been studied for antidiabetic potential; however, no efforts have been made to explore the potential of this mushroom to influence carbohydrate metabolizing enzymes viz. α-amylase and α-glucosidase. The present work was undertaken to investigate the inhibitory potential of Pleurotus ostreatus cv. Florida on enzymes α-amylase and α-glucosidase. Several concentrations of extracts were used to study inhibition of enzymatic activity of α-amylase and α-glucosidase. A dose dependent inhibitory effect on enzymes was observed. The current study, for the first time, uncovered α-amylase and α-glucosidase inhibitory potential of Pleurotus ostreatus cv. Florida. The study could be helpful to isolate and characterize compounds responsible for it. [ABSTRACT FROM AUTHOR]

Many current studies show an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, correcting inflammation may be beneficial to stop, impede, and improve diabetes status and its associated complications. Apart from anti-inflammatory drugs, various hypoglycaemic agents have also been found to reduce inflammation that could contribute to improved outcomes in diabetic patients. Various studies have been carried out with thiazolidinediones, dipeptidyl peptidase-4 inhibitors and Metformin showing moderateto-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors exert modest antiinflammatory effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is paucity of human clinical data on anti-inflammatory effects of sodium-glucose cotransporter type-2 (SGLT) inhibitors. Nevertheless, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the glucose-lowering agents. Also, it is important to define what role the anti-inflammatory effects of these anti-diabetic agents may play in the prevention of macrovascular and microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Recently, the strategy of multivalency has been widely employed to design glycosidase inhibitors, as glycomimetic clusters often induce marked enzyme inhibition relative to monovalent analogs. Polyhydroxylated pyrrolidines, one of the most studied classes of iminosugars, are an attractive moiety due to their potent and specific inhibition of glycosidases and glycosyltransferases, which are associated with many crucial biological processes. The development of multivalent pyrrolidine derivatives as glycosidase inhibitors has resulted in several promising compounds that stand out. Herein, we comprehensively summarized the different synthetic approaches to the preparation of multivalent pyrrolidine clusters, from total synthesis of divalent iminosugars to complex architectures bearing twelve pyrrolidine motifs. Enzyme inhibitory properties and multivalent effects of these synthesized iminosugars were further discussed, especially for some less studied therapeutically relevant enzymes. We envision that this comprehensive review will help extend the applications of multivalent pyrrolidine iminosugars in future studies. [ABSTRACT FROM AUTHOR]

Phytochemical study of the root bark of Paeonia suffruticosa plant led to the isolation and characterization of paeoniflorigenone (1), benzoylpaeoniflorin (2), betulinic acid (3), oleanolic acid (4), β-sitosterol (5), and caffeic acid octadecyl ester (6). The enzymatic activities of compounds 1-6 were evaluated by in vitro inhibition assay of α-glucosidase and α-amylase. Compounds 1-6 with IC50 values ranging from 30 to 180 μM inhibited α-glucosidase more efficiently than the standard compound acarbose (IC50 = 1463.0 ± 29.5 μM). Conversely, these compounds (with IC50 values ranging from 40 to 200 μM) were less potent against α-amylase compared to acarbose (IC50 = 16.6 ± 0.9 μM). Kinetic analysis showed that compound 1 was a mixed-type inhibitor, compounds 3 and 4 were noncompetitive inhibitors, while compound 6 was an uncompetitive inhibitor of glucosidase. [ABSTRACT FROM AUTHOR]

Background: Current evidence of the association between the use of sulfonylurea and cancer risk is highly conflicting and little evidence of this association is from the mainland Chinese population. This study aimed to evaluate the potential effects of sulfonylurea use on cancer risk among patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study of T2DM patients who were new users of sulfonylurea or metformin was conducted using the Yinzhou Regional Health Care Database. A marginal structural Cox model was used to estimate the hazard ratio (HR) of cancer associated with the use of sulfonylurea compared with metformin, with time-varying confounders controlled by inverse probability weighting. Secondary analyses using different glucose-lowering drugs (GLDs) as comparator and sensitivity analyses for potential bias due to latency period, model misspecification, missing data, analyses strategy (intention-to-treat and per-protocol), and diagnosis validation were performed to examine the robustness of the results. Results: After fully controlling for time-varying confounding, baseline confounding, and competing risk, the use of sulfonylurea was not associated with the risk of any cancer (HR 1.09; 95% CI, 0.93–1.27), compared with the use of metformin. In the secondary analyses, compared with α - glucosidase inhibitors, thiazolidinediones, glinides, other GLDs except sulfonylure and insulin, and T2DM patients not treated with sulfonylureas, the HRs of the association between sulfonylurea use and cancer risk were 0.92 (95% CI; 0.78–1.08), 0.89 (95% CI; 0.66–1.19), 0.85 (95% CI; 0.71–1.02), 1.04 (95% CI; 0.89–1.22), and 1.07 (95% CI; 0.99–1.16), respectively. The results of analyses for various subgroups, risk of site-specific cancers, cumulative duration, dose-response relationship, and sensitivity analyses of different latency periods and missing data were generally consistent with the findings of the primary analyses. Conclusion: No association between sulfonylurea use and cancer risk was found in this study after properly controlling biases due to time-varying confounders and other sources. Further studies on the association between sulfonylurea use and the risk of cancer by using data from a Chinese population with higher representativeness are needed. [ABSTRACT FROM AUTHOR]

• Pleurospermum candollei possess high inhibition activity against DPPH radicals and alpha glucosidase enzyme. • P. candollei can reduce the diabetic effects of streptozotocin. • P. candollei can normalize the production of antioxidant enzymes and free radicals in rat kidney. • P. candollei can regulate the inhibition of inflammatory, and apoptotic mediators. • P. candollei can be used as potent drug against diabetes induced nephropathy. Pleurosepermum candollei is a local vegetable that is traditionally used to cure abdominal problems, pain, and infertility. The purpose of this study was to evaluate the therapeutic potential of P. candollei ethanolic extract against T2DM through modulation of renal genetic markers. Biochemical composition of extract was investigated through high performance liquid chromatography and quantitative phytochemical analyses. In rats, T2DM was induced by injecting streptozotocin (STZ), and P. candollei ethanol extract was administered for 21 days. Antioxidant enzymes and renal biomarkers were assessed in homogenized kidney samples of treated groups. qRT-PCR analysis of isolated RNA was performed for estimation of inflammatory and apoptotic markers. These biochemical analyses revealed that plant extract significantly normalized the levels of catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) after 21 days of treatment. However, high dose of plant extract (300 mg/kg) exhibited more prominent results in restoring the inflammatory (IL-6, IL-β1, and TNF-α) and apoptotic markers than low dose (150 mg/kg). Similarly, histological studies also revealed that there was minor inflammation and necrosis in kidney of plant treated rats. Generally, the present study showed that administration of P. candollei extract exhibits renal protective, anti-hyperglycemic, and anti-glycation properties. However, further research is required to assess the mechanism of action of PCE at clinical level. [Display omitted] [ABSTRACT FROM AUTHOR]

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Bryophyllum delagoense (Eckl. & Zeyh.) Druce, native to Madagascar, is popularly known as "abyssian cactus" and popularly used in folk medicine as an analgesic and healing agent. The study methodology was divided into the phytochemical study: fractionation and identification of phenolic compounds by HLPC-ESI-MS/MS from the methanolic extract (ME), and fractions (DCMF and EAF) of leaves of B. delagoense, and biological activity with acetylcholinesterase and α-glucosidase inhibition of extracts and fractions by in vitro enzymatic techniques. Twenty-seven phenolic compounds were identified, being the highest concentration of syringic acid (87.848 mg g−1). The DCMF fraction showed the best biological activity for inhibition of α-glucosidase enzyme (0.125 mg mL−1). [ABSTRACT FROM AUTHOR]

The article discusses the alpha-glucosidase inhibitors and thiazolidinediones that are older classes of oral type 2 diabetes medication. Topics discussed include acarbose that is an alpha-glucosidase inhibitor available in Australia, diagnosis of impaired glucose tolerance, and safety concerns which were raised about the use of rosiglitazone.

The focus of the presented study is the in vitro anti-oxidant activity and anti-diabetic potential of water extracts from the following four herbal substances, not traditionally used for treatment of diabetes mellitus – leaves of Sambucus ebulus L. and Prunus mahaleb L., and flowering stems of Cichorium intybus L. and Satureja kitaibelii Wierzb. ex Heuff. The water extracts are obtained through ultrasonication. The extract of S. kitaibelii stands out due to its highest values in all studied indicators – total phenolic content, scavenging potential (DPPH, ABTS) and α-glucosidase inhibitory activity which was six times higher than acarbose. The extract of C. intybus also showed significant α-glucosidase inhibitory activity compared to acarbose. The flowering stems of both species are promising sources of biologically active substances for blood sugar control in diabetes mellitus. [ABSTRACT FROM AUTHOR]

Vascular aging is defined as organic and functional changes in blood vessels, in which decline in autophagy levels, DNA damage, MicroRNA (miRNA), oxidative stress, sirtuin, and apoptosis signal-regulated kinase 1 (ASK1) are integral thereto. With regard to vascular morphology, the increase in arterial stiffness, atherosclerosis, vascular calcification and high amyloid beta levels are closely related to vascular aging. Further closely related thereto, at the cellular level, is the aging of vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Vascular aging seriously affects the health, economy and life of patients, but can be delayed by SGLT2 inhibitors through the improvement of vascular function. In the present article, a review is conducted of recent domestic and international progress in research on SGLT2 inhibitors, vascular aging and diseases related thereto, thereby providing theoretical support and guidance for further revealing the relationship between SGLT2 inhibitors and diseases related to vascular aging. [ABSTRACT FROM AUTHOR]

Introduction: Merremia peltata is ethnomedicine plant used as traditional medicine in Sulawesi, Sumatra, Maluku and Papua. M. peltata is used for diabetic. Diabetes mellitus therapy with inhibit activity of alpha glucosidase enzyme could delay absorption of monosaccharides after a meal and interrupt glucose transport into the circulation. Objective: This research purpose is to investigate in vitro antioxidant activity and alpha glucosidase enzyme inhibitor leaves and stem extract of M. peltata. Method: The Stem and leaves of M. peltata were extracted sequentially using the UAE method using hexane, ethyl acetate, and methanol as mobile phase/solvent. The M. peltata extracts were subjected to the antioxidant activity assay by the DPPH radical scavenging and FRAP method. Antidiabetic activity was determined by an enzymatic alpha glucosidase inhibitor. Result: The extract which had best performance in antioxidant activity was stem ME with value of IC50 in DPPH 47.41 μg/mL and total antioxidant power 340.04 μmol/g. This study showed that leaves and stem extract of M .peltata have potential alpha glucosidase inhibitors for diabetic therapy. Stem ME had the best activity with IC50 value 47.44 μg/mL, almost two times better than acarbose as a positive control (IC50 = 98.38 μg/mL). Leaves ME, leaves EA, and stem EA also give better activity of alpha glucosidase inhibitors than acarbose with IC50 value 67.24 μg/mL, 69.38 μg/mL, and 72.85 μg/mL, respectively. Conclusion: M. peltata has potential antioxidant and alpha glucosidase inhibitor activity for diabetic therapy. [ABSTRACT FROM AUTHOR]

Mangrove is one of the highly productive ecosystems and contains diverse plants and microbial communities. Bacterial endophytes from mangroves are considered as a prolific source of biological molecules with important functions in the protection of mangrove plants against herbivores, insects as well as pathogens. The present study aimed to isolate endophytic bacteria from the roots of mangrove plant Rhizophora stylosa and to screen antioxidant, α-amylase and α- glucosidase inhibitory activities of ethyl acetate extracts from the isolated endophytic bacteria. A total of 73 endophytic bacterial strains from R. stylosa roots were isolated, of which ethyl acetate extracts of 10 isolated endophytic strains at a concentration of 500 µg/mL showed antioxidant activity with ATBS and DPPH radical scavenging values ranging from 31.3 ± 2.5% to 62.2 ± 6.3% and 21.2 ± 3.2% to 56.7 ± 4.5%, respectively. Additionally, the ethyl acetate extracts of 11 isolated endophytic bacteria at a concentration of 500 µg/mL exhibited α-amylase and α- glucosidase inhibitory activities with values ranging from 31.4 ± 3.1% to 59.7 ± 6.4% and 17.3 ± 3.1% to 54.5 ± 6.1%, respectively. The identification of the five high antioxidant, α-amylase and α-glucosidase inhibitory endophytes by 16S rRNA sequences revealed that the bacterial endophytes belonged to three genera, including Bacillus, Streptomyces, and Pseudovibrio with the similarity of more than 99%. The obtained results suggest that the root endophytic bacteria of R. stylosa are a source of antioxidant and antidiabetic agents. To the best of our knowledge, this is the first report of antioxidant, α-amylase and α-glucosidase activities of the endophytic bacteria from the roots of Vietnam mangrove plants in general and R. stylosa in particular. [ABSTRACT FROM AUTHOR]

In an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results. [ABSTRACT FROM AUTHOR]

Iminosugar compounds are monosaccharide mimetics with broad but generally weak antiviral activities related to inhibition of enzymes involved in glycobiology. Miglustat (N-butyl-1-deoxynojirimycin), which is approved for the treatment of lipid storage diseases in humans, and UV-4 [N-(9-methoxynonyl)-1-deoxynojirimycin] inhibit the replication of hepatitis A virus (HAV) in cell culture (50% inhibitory concentrations [IC50s] of 32.13mM and 8.05mM, respectively) by blocking the synthesis of gangliosides essential for HAV cell entry. We used a murine model of hepatitis A and targeted mass spectrometry to assess the capacity of these compounds to deplete hepatic gangliosides and modify the course of HAV infection in vivo. Miglustat, given by gavage to Ifnar12/2 mice (4,800mg/kg of body weight/day) depleted hepatic gangliosides by 69 to 75% but caused substantial gastrointestinal toxicity and failed to prevent viral infection. UV-4, similarly administered in high doses (400mg/kg/day), was well tolerated but depleted hepatic gangliosides by only 20% after 14 days. UV-4 depletion of gangliosides varied by class. Several GM2 species were paradoxically increased, likely due to inhibition of β-glucosidases that degrade gangliosides. Both compounds enhanced, rather than reduced, virus replication. Nonetheless, both iminosugars had surprising anti-inflammatory effects, blocking the accumulation of inflammatory cells within the liver. UV-4 treatment also resulted in a decrease in serum alanine aminotransferase (ALT) elevations associated with acute hepatitis A. These anti-inflammatory effects may result from iminosugar inhibition of cellular α-glucosidases, leading to impaired maturation of glycan moieties of chemokine and cytokine receptors, and point to the potential importance of paracrine signaling in the pathogenesis of acute hepatitis A. [ABSTRACT FROM AUTHOR]

Jamun (Syzygium cumini L.) seed is one of the rich sources of polyphenolic compounds with antioxidant potential and α-glucosidase inhibitory activity. A study was conducted to optimize the methodology for the extraction of polyphenolic compounds (total phenolic and flavonoid contents) with antioxidant potential and α-glucosidase inhibitory activity from jamun seed powder. The study showed that the nature of solvent and extraction conditions had a significant effect on total phenolic content (TPC), total flavonoid content (TFC), antioxidant potential, and α-glucosidase inhibitory activity. The TPC varied between 6.0 (mg/g jamun seed powder) for the acetone extract to 119.2 (mg/g) for 80% aqueous acetone extract, and TFC varied between 1.06 mg/g for the acetone to 10.81 mg/g for the 80% aqueous methanol. From the study, it was apparent that an aqueous form of acetone (acetone: water 80:20, v/v) is a better solvent system for extraction of polyphenolic compounds with high antioxidant potential and α-glucosidase inhibitory activity. Ultrasonication for 60 min increased the efficiency of phenolic extraction. [ABSTRACT FROM AUTHOR]

Natural products have been widely used in the treatment of type 2 diabetes (T2D). However, their mechanisms are often obscured due to multi‐components and multi‐targets. The authors constructed a pathway‐based protein–protein association (PPA) network for target proteins of 13 α‐glucosidase inhibitors (AGIs) identified from Scutellaria baicalensis Georgi (SBG), designed to explore the underlying mechanisms. This network contained 118 nodes and 1167 connections. An uneven degree distribution and small‐world property were observed, characterised by high clustering coefficient and short average path length. The PPA network had an inherent hierarchy as C(k)∼k−0.71. It also exhibited potential weak disassortative mixing pattern, coupled with a decreased function Knn (k) and negative value of assortativity coefficient. These properties indicated that a few nodes were crucial to the network. PGH2, GNAS, MAPK1, MAPK3, PRKCA, and MAOA were then identified as key targets with the highest degree values and centrality indices. Additionally, a core subnetwork showed that chrysin, 5,8,2′‐trihydroxy‐7‐methoxyflavone, and wogonin were the main active constituents of these AGIs, and that the serotonergic synapse pathway was the critical pathway for SBG against T2D. The application of a pathway‐based protein–protein association network provides a novel strategy to explore the mechanisms of natural products on complex diseases. [ABSTRACT FROM AUTHOR]

Recently, the strategy of multivalency has been widely employed to design glycosidase inhibitors, as glycomimetic clusters often induce marked enzyme inhibition relative to monovalent analogs. Polyhydroxylated pyrrolidines, one of the most studied classes of iminosugars, are an attractive moiety due to their potent and specific inhibition of glycosidases and glycosyltransferases, which are associated with many crucial biological processes. The development of multivalent pyrrolidine derivatives as glycosidase inhibitors has resulted in several promising compounds that stand out. Herein, we comprehensively summarized the different synthetic approaches to the preparation of multivalent pyrrolidine clusters, from total synthesis of divalent iminosugars to complex architectures bearing twelve pyrrolidine motifs. Enzyme inhibitory properties and multivalent effects of these synthesized iminosugars were further discussed, especially for some less studied therapeutically relevant enzymes. We envision that this comprehensive review will help extend the applications of multivalent pyrrolidine iminosugars in future studies.

Purpose: To compare the safety and efficacy of once-weekly prescription of GLP-1 receptor agonists (adlyxin) with those of α-glucosidase inhibitor (voglibose) and other reference drugs (RD). Methods: A total of 1250 stable diabetes-mellitus patients from the Department of Endocrinology, Ningbo No. 6 Hospital, Ningbo, Zhejiang 315040, China were enrolled in this study between Feb 2018 and Jan 2020. They were treated using physical exercise and diet chart therapy. The patients were assigned to three different groups and administered GLP-1 receptor agonist (GLP-1RA) or glucosidase inhibitor (voglibose) and other reference drugs (RDs). The safety and efficacy of these drugs were compared. The primary endpoint was the number of treatment-emergent adverse events (TEAEs), while the secondary endpoints were based on symptomatic hypoglycaemic episodes and other biochemical parameters. Results: Patients who used α-glucosidase inhibitors had the highest percentage of TEAEs, when compared to those on GLP-1RAs and RDs (p < 0.05). No specific cases of severe hypoglycaemia were observed among all the groups. Users of adlyxin also achieved significant glycaemic control at the end of the study period, when compared to voglibose users, with a mean HbA1c baseline of 8.2 % (p < 0.05). Conclusion: These results indicate that the GLP-1 receptor agonist adlyxin achieved good glycaemic control. Thus, it has beneficial potential for use among type 2 diabetes in the Chinese population. [ABSTRACT FROM AUTHOR]

An alpha-glucosidase inhibitor Voglibose is used for lowering blood glucose levels in people with diabetes A very straight forward, quick, responsive and accurate UV-Spectrophotometric method of analysis have been developed for assessment of Voglibose in pharmaceutical formulation. Since Voglibose only absorbs UV in the low wavelength area, it cannot be identify with high sensitivity. Voglibose has shown successful results for various analytical instruments only in the permutation of Taurine and Sodium periodate. The API was derivatives using Taurine and Sodium periodate in water and methanol. Drug exhibited distinct λmax in methanol at 281nm. Linearity was observed in the concentration range 10-80 µg/ml. The method was validated by recovery studies. The methods used are inexpensive and sensitive for the inference of Voglibose in bulk drug and tablet dosage forms. [ABSTRACT FROM AUTHOR]

Spices and herbs are used in Asian traditional beverages (ATB) mainly for gastronomic purposes, i.e., main flavoring, aroma enhancer, and colorant, but not for health functionality. Twenty-two selected spices and herbs used in ATB were evaluated for their antioxidant level, antidiabetic potential, and the possible risk of coumarin toxicity. Pattern recognition methods were applied to the data collection using principal component analysis (PCA) and hierarchical clustering analysis (HCA) to investigate the assay and spices and herbs inter-relationship. The evaluation made can help in the future selection of spice and herb ingredients with high antioxidant and antidiabetic properties and a safe limit of coumarin to be used in developing a reformulated ATB. The spice and herb selections were based on the determination of polyphenol content, antioxidant (DPPH, ORAC, and FRAP analyses) levels, AGI activities, and coumarin content aqueous extracts. Five out of 10 aqueous extracts of main flavoring spices (Ceylon cinnamon, cassia, clove, star anise, and mace), 1 out of 7 extracts of aroma enhancers (rose), and 2 out of 5 colorant extracts (sappan heartwood and black myrobalan) exhibited profound antioxidant and α-glucosidase inhibition (AGI) activities. PCA and HCA indicated that the black myrobalan extract had the most distinct and potent antioxidant and AGI activities among the tested extracts (DPPH IC50 37.61 ± 1.48 mg/mL, DPPH 126.15 ± 0.65 Trolox equivalent μg/mL, FRAP 52.66 ± 0.8 Trolox equivalent mM/mL, ORAC 18,213.33 ± 298.91 Trolox equivalent μM/mL; and AGI 1306.98 ± 21.38 tannic acid equivalent μg/mL). On the contrary, cardamom extract showed the least of both activities. Ambrette seed and cassia extracts had considerably high coumarin contents, which is higher than the permissible limit of 10 mg/kg. This study revealed that black myrobalan is an indispensable functional ingredient in an Asian traditional beverage. However, the use of cassia and ambrette seeds shall be a caution to lower the risk of possible coumarin toxicity. PCA and HCA enabled the visualization of the complicated relationship between the antioxidant - antidiabetic properties and each spice/herb ingredient. This recognition method eased the functional ingredient selection in the next polyherbal formulation step. [ABSTRACT FROM AUTHOR]

Background/objectives: Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses. Methods: We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models. Results: The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (−1.5 mmol/l mean PPG [95% CI −1.9, −1.1] by acarbose, and −1.6 [−1.9, −1.4] by miglitol) as compared to individuals without diabetes (−0.4 [95% CI −0.5, −0.3] by acarbose, and −0.6 [−0.8, −0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43−54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes. Conclusions: The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a chronic disease with a growing prevalence worldwide. In addition to the conventional therapy, many T2D patients use phytotherapeutic preparations. In the present study, chemical composition, antioxidant, and α-glucosidase inhibiting activity of traditional antidiabetics from Croatian ethnomedicine (Achillea millefolium, Artemisia absinthium, Centaurium erythraea, Morus alba, Phaseolus vulgaris, Sambucus nigra, and Salvia officinalis) were assessed. The efficacy of water and 80% ethanol as extraction solvents for bioactive constituents was compared. HPLC analysis revealed that the prepared extracts were rich in phenols, especially rutin, ferulic, and chlorogenic acid. Antiradical (against DPPH and ABTS radicals), reducing (towards Mo6+ and Fe3+ ions), and enzyme inhibiting properties were in linear correlation with the content of phenolic constituents. Ethanolic extracts, richer in phenolic substances, showed dominant efficacy in those assays. Aqueous extracts, on the other hand, were better Fe2+ ion chelators and more active in the β-carotene linoleic acid assay. Extracts from S. officinalis and A. millefolium were particularly active antioxidants and α-glucosidase inhibitors. A. absinthium, another potent α-glucosidase inhibitor, contained chromium, a mineral that promotes insulin action. The investigated plants contained significant amounts of minerals useful in management of T2D, with negligible amounts of heavy metals deeming them safe for human use. [ABSTRACT FROM AUTHOR]

Background: Sialidase has an important role in the pathogenesis of periodontitis and Porphyromonas gingivalis is a sialidase-producing organism implicated in periodontitis development. The aim of this study was to evaluate the anti-virulence and anti-inflammatory properties of the sialidase inhibitor, 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (DANA), in vitro and in vivo.Methods: The effects of DANA on P. gingivalis sialidase and cell viability were determined, and the effects of DANA on P. gingivalis virulence were evaluated by assessment of growth curves, cell morphology, biofilm formation, fimbriae gene expression, and gingipains and lipopolysaccharide (LPS) activity. Anti-inflammatory effects of DANA on LPS-induced macrophages were assessed by measurement of tumor necrosis factor-alpha (TNF-α), interleukin (IL-1β), inducible nitric oxide synthase (iNOS) secretions. The effect of DANA on P. gingivalis-induced periodontitis in rats was analyzed by radiography, stereoscopic microscopy, histopathology, and immunohistochemistry.Results: Sialidase inhibition rate of 1mM DANA was 72.01%. Compared with untreated controls, treatment with DANA inhibited P. gingivalis growth and biofilm formation, and significantly decreased expression of the fimA, fimR, and fimS genes, as well as gingipains activity. DANA did not influence macrophage viability, but significantly inhibited TNF-α, IL-1β, and iNOS production in LPS-stimulated macrophages. In the periodontitis rat model, DANA prevented alveolar bone absorption and inhibited TNF-α and IL-1β production.Conclusion: DANA can reduce the growth, the biofilm formation and the virulence of P. gingivalis and exhibits anti-inflammatory effects, as well as effects against rat periodontitis, suggesting that DANA should be considered for development as a new adjunctive treatment for periodontitis. [ABSTRACT FROM AUTHOR]

This study evaluates the anti-diabetic and anti-oxidative potential of oil extracts from four Iranian medicinal plants, namely Oliveria decumbens, Thymus kotschyanus, Trachyspermum ammi, and Zataria multiflora, obtained by simulated in vitro gastrointestinal digestion. The phytochemical analysis showed that oil extracts are rich in active substances such as phenolic compounds and essential fatty acids. In specific, they are rich in carvacrol, thymol, and functional polyunsaturated fatty acids, including linoleic and α-linolenic acids. This study demonstrated that, oil extracts from these plants exhibit moderate anti-glucose oxidation, anti-lipid peroxidation, anti-protein oxidation, and anti-protein glycation, also with a semi-strong capacity for anti-amylase and anti-glucosidase activity. These effects may be due to considerable potentials of these compounds in metal ions and free hydroxyl radicals scavenging, as well as competitive and mixed non-competitive inhibition of α-amylase and α-glucosidase activities. [ABSTRACT FROM AUTHOR]

This study examined the ability of ackee arils flour to serve as substitute for margarine in cookies production and the possibility of employing wheat-ackee arils cookies as functional food. Four samples of cookies were formulated, which include; the control, cookies with 30 g margarine (NAFC), cookies with 20 g margarine + 10 g ackee arils flour (AF1), cookies made with 10 g of margarine + 20 g of ackee arils flour (AF2), and cookies prepared from 30 g ackee arils flour (AF3). Wheat-ackee arils cookies were evaluated for physico-chemical properties, α-amylase and α-glucosidase inhibitory activities along with glycemic load and glycemic index. The energy values of the cookies ranged from 428.74 kcal/100 g in AF3 to 450.22 kcal/100 g in AF1, the energy values of samples were significantly (p < 0.05) lower when compared with control NAFC. The result of the cookies diameter revealed that sample AF3 have the highest mean diameter value (5.13 cm) while NAFC the control sample had the least mean value of (3.26 cm). Ackee arils cookies extract influenced the in-vitro inhibitory properties of α-amylase and α-glucosidase linked to type 2 diabetic mellitus. A combination of 20 g ackee aril and 10 g margarine showed the highest inhibitory effect of 51.35%-90.54% from 50 µg/mL- 200 µg/mL concentration for α-amylase and α-glucosidase. It may be concluded that ackee arils flour can serve as a replacement for margarine in cookies production and wheat-ackee aril cookies may be considered as a functional food. [ABSTRACT FROM AUTHOR]

This investigation aimed to evaluate the phytochemical constituents, antioxidant, antibacterial and α-glucosidase inhibitory activities of A. tomentosa essential oil. The essential oil extracted using steam distillation method possessed antibacterial activity for all tested bacteria. Comparing to cefaclor the percentage of relative inhibition zone diameter (RIZD) was 100.30 ± 4.73 % for Staphylococcus aureus and ranged between 79.67 ± 3.79 % and 84.33 ± 4.16 % for other bacteria. The essential oil showed considerable antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, ferric reducing antioxidant power (FRAP) assay and metal chelating methods, the EC50 of the essential oil were 72.06 ± 3.99, 54.69 ± 4.69 and 50.39 ± 2.86 µg/ml respectively, comparing 7.34 ± 2.43, 10.87 ± 3.34 and 14.50 ± 3.46 µg/ml for positive controls (Trolox, EDTA and Quercetin respectively). The essential oil also possessed concentration dependent α-glucosidase inhibitory activity with EC50 149.20 ± 7.63 µg/ml comparing to acarabose EC50 14.50 ± 3.46 µg/ml. Forty compounds were identified depending in retention index (RI) and mass spectra (MS) that form 96.31 % of the essential oil composition. The result showed that the ratio of the identified compounds range between 0.11 % and 23.72 %, 3-Carene (23.72 %), Limonene (12.19 %) and α-Terpinyl acetate (10.22%) were found to be the major components of the essential oil. m-Cyneme (7.11 %) and Di-n-octyl phthalate (4.50 %) present in moderate quantities. The phytochemical analyzes showed that the identified compound quantitatively and qualitatively differ from the previous study that investigate the composition of A.tomentosa L. essential oil. [ABSTRACT FROM AUTHOR]

Inhibition of α -glucosidase activity is an effective way for treatment of type 2 diabetes mellitus. Epimedii Folium is an important source of α -glucosidase inhibitors (AGIs), however bioactive compounds and pharmacological mechanisms remained unclear. In this study, a novel strategy was established, which harnessed α -glucosidase functionalized magnetic beads to fish out potential AGIs, followed by UPLC-MS/MS analysis for their identification. Furthermore, molecular docking was employed to predict binding patterns between the AGIs and the enzyme, and IC 50 values was estimated as well. After response surface methodology optimization, the highest activity of Fe 3 O 4 @ α -glucosidase has been achieved when 1.17 mg/mL of α -glucosidase was immobilized in phosphate buffer (pH 6.81) for 4.22 h. Moreover, eight flavonoids were fished out from the extract of Epimedii Folium , and then identified to be epimedin A, epimedin B, epimedin C, icariin, sagittatoside A, sagittatoside B, 2"-O-rhamnosyl icariside II and baohuoside I. All of them were further confirmed to be AGIs through in vitro inhibitory assay and molecular docking. Among those, baohuoside I and sagittatoside B possessed stronger inhibitory activity than acarbose. The approach has a significant prospect in conveniently screening bioactive compounds that target various receptors, which provided an efficient platform for new drug development from natural products. Unlabelled Image • Fe 4 O 3 @ α -glucosidase magnetic nanoparticles for ligand fishing were constructed. • The novel approach is promising to screen bioactive compounds from herbal products. • Eight flavonoids as α -glucosidase inhibitors were fished out from Epimedii Folium. • Baohuoside I and sagittatoside B exhibited higher inhibitory activity than acarbose. [ABSTRACT FROM AUTHOR]

The strategy of reducing carbohydrate digestibility by controlling the activity of two hydrolyzing enzymes (α‐amylase and α‐glucosidase) to control postprandial hyperglycemia is considered as a viable prophylactic treatment of type 2 diabetes mellitus (T2DM). Thus, the consumption of foods rich in hydrolyzing enzyme inhibitors is recommended for diet therapy of diabetes. Whole cereal products have gained increasing interests for plasma glucose‐reducing effects. However, the mechanisms for whole cereal benefits in relation to T2DM are not yet fully understood, but most likely involve bioactive components. Cereal‐derived phenolic compounds, peptides, nonstarch polysaccharides, and lipids have been shown to inhibit α‐amylase and α‐glucosidase activities. These hydrolyzing enzyme inhibitors seem to make whole cereals become nutritional strategies in managing postmeal glucose for T2DM. This review presents an updated overview on the effects provided by cereal‐derived ingredients on carbohydrate digestibility. It suggests that there is some evidence for whole cereal intake to be beneficial in amelioration of T2DM through inhibiting α‐glucosidase and α‐amylase activities. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of diabetes mellitus type 2 in the world is more than 230 million people, increases about 3% in a year. Kayu Sarampa or Nyirih batu (Xylocarpus moluccensis (Lam.) M. Roen) has traditionally been used to treat diabetic patient by native people in Ratahan, North Celebes, Indonesia. Therefore, this research was sequentially extracted bioactive component from stem bark of kayu sarampa showed alpha glucosidase inhibitor. Objective: To assess antioxidants and alpha glucosidase inhibitory activity of hexane, ethyl acetate, and methanol extract from stem bark of Kayu Sarampa. Method: The Stem bark was extracted with Reflux method using hexane, ethyl acetate, and methanol as mobile phae/solvent. The Hexane Extract (HE), Ethyl Acetic Extract (EAE) and Methanol Extract (ME) were subjected to the antioxidant activity assay by the 2.2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and the ferric-reducing antioxidant power (FRAP) method. Antidiabetic activity was determined by enzymatic alpha-glucosidase inhibitor. Results: The extract which had the highest activity based on the DPPH test and FRAP test was the ME compared with EAE, and HE with IC50 values of 16.51 µg/mL, 34.10 51 µg/mL, and 38.82 51 µg/mL, respectively. Ferrous equivalent antioxidant capacity (FeEAC) method, methanolic extract had a higher reduction capacity than the EH and EEA which were 148.96 µmol/gr, 48.96 µmol/gr, and 148.96 µmol/gr, respectively. The result showed that kayu sarampa stem bark exhibited antidiabetic activity due to its high inhibition compared with control (acarbose). ME showed inhibition of 53,11% followed with EAE 49,7%, HE 44,53%, and acarbose as control 29,32%.Conclusion: stem bark of kayu sarampa have bioactive component as alpha glucosidase inhibitor. [ABSTRACT FROM AUTHOR]