Inhibition Of Digestive Enzymes Research Articles

Sekikaic acid modulates pancreatic β-cells in streptozotocin-induced type 2 diabetic rats by inhibiting digestive enzymes

The antioxidant and antidiabetic effects of sekikaic acid (SA) were investigated using in vitro and in vivo study models. SA possessed good antioxidant activity as assessed through hydroxyl radicals (IC50 value = 41.5 µg/mL) and ferric ions assay (IC50 value = 42.0 µg/mL). SA exhibited stronger α-glucosidase and α-amylase inhibition than that of aldose-reductase and protein tyrosine phosphatase 1B. The hypoglycemic activity of SA caused significant reduction of plasma glucose levels in normal and glucose loaded rats. The anti-hyperglycemic activity of SA (2 mg/Kg body weight) was indicated by the reduction of blood glucose by 44.17 ± 3.78% in the third week in streptozotocin-induced diabetic rats. The hypolipidaemic action of SA was evident by the significant decrease in the levels of low-density lipoprotein, total cholesterol, and total glycerides. Histologically, the pancreas of the treated groups showed significant regeneration of the pancreatic β-cells compared to diabetic control, possibly due to the inhibition of digestive enzymes.

Dietary polyphenols as antidiabetic agents: Advances and opportunities

AbstractDietary polyphenols have been widely investigated as antidiabetic agents in cell, animals, human study, and clinical trial. The number of publication (Indexed by Web of Science) on “polyphenols and diabetes” significantly increased since 2010. This review highlights the advances and opportunities of dietary polyphenols as antidiabetic agents. Dietary polyphenols prevent and manage Type 2 diabetes mellitus via the insulin‐dependent approaches, for instance, protection of pancreatic islet β‐cell, reduction of β‐cell apoptosis, promotion of β‐cell proliferation, attenuation of oxidative stress, activation of insulin signaling, and stimulation of pancreas to secrete insulin, as well as the insulin‐independent approaches including inhibition of glucose absorption, inhibition of digestive enzymes, regulation of intestinal microbiota, modification of inflammation response, and inhibition of the formation of advanced glycation end products. Moreover, dietary polyphenols ameliorate diabetic complications, such as vascular dysfunction, nephropathy, retinopathy, neuropathy, cardiomyopathy, coronary diseases, renal failure, and so on. The structure–activity relationship of polyphenols as antidiabetic agents is still not clear. The individual flavonoid or isoflavone has no therapeutic effect on diabetic patients, although the clinical data are very limited. Resveratrol, curcumin, and anthocyanins showed antidiabetic activity in human study. How hyperglycemia influences the bioavailability and bioactivity of dietary polyphenols is not well understood. An understanding of how diabetes alters the bioavailability and bioactivity of dietary polyphenols will lead to an improvement in their benefits and clinical outcomes.

Disintegration and Dissolution Testing of Green Tea Dietary Supplements: Application and Evaluation of United States Pharmacopeial Standards

Approved performance quality tests are lacking in the United States Pharmacopeia (USP) for dietary supplements (DSs) containing green tea extracts. We evaluated the applicability of USP <2040 > general chapter protocols for disintegration and dissolution testing of botanicals to GT DSs. Of 28 single-ingredient GT DSs tested in 2 to 4 lots, 9 (32.1%) always passed the disintegration test, 8 (28.6%) always failed, and 11 (39.3%) showed inconsistent results. Of 34 multi-ingredient DSs tested in 2 lots, 21 (61.8%) passed and 8 (23.5%) failed in both lots, and 5 (14.7%) exhibited inconsistent performance. When stronger destructive forces were applied (disk added), all of the capsules that had failed initially, but not the tablets, passed. In dissolution testing, for the release of epigallocatechin-3-gallate (EGCG), only 6 of 20 single-ingredient DSs passed. Unexpectedly, with the addition of pepsin (prescribed by USP), only one additional DS passed. These results raise concerns that EGCG was not released properly from GT DS dosage forms. However, the general USP protocols may be inadequate for this botanical. More biorelevant destructive forces may be needed to break down capsules and tablets strengthened by the EGCG’s interaction with shell material and to overcome the inhibition of digestive enzymes by EGCG.

Interactions between phenolic compounds, amylolytic enzymes and starch: an updated overview

Polyphenols are reported to modulate starch digestibility via either direct inhibition of alpha-glycosidase digestive enzymes and/or the formation of inclusion and non-inclusion complexes with starch. In particular, the former process results from binding interactions between phenolics and the free enzymes. Concerning the latter process, recent evidences support specific non-covalent bonds between different polyphenols (mainly flavonoids, phenolic acids and tannins) and carbohydrate polymers via hydrogen bonds and hydrophobic interactions. This role played by phenolics towards starch digestibility could represent a valid strategy to design functional foods and/or to manage type II diabetes. This short-review provides an updated and critical overview on the complex interactions occurring between phenolic compounds and amylolytic enzymes within the food-matrix and during food digestion, together with the postulated effects provided by polyphenols-starch interactions on starch digestibility. Noteworthy, considering that the most recent works on this topic are from in vitro studies, further in vivo research is deserved.

In vitro evaluation of digestive enzyme inhibition and antioxidant effects of naked oat phenolic acid compound (OPC)

SummaryThis research was focused on digestive enzyme inhibition and antioxidant properties of naked oat phenolic acid compound (OPC). Free and bound phenolic acid were separated from ethyl acetate fraction, n‐butanol fraction and aqueous fraction. The interactions between OPC and main digestive enzymes (α‐amylase, α‐glucosidase, pepsin and trypsin) were studied. It was shown that the semi‐purified bound phenolic acid (semi‐purified by AB‐8 column) has a competitive alpha‐glucosidase inhibitor, while OPC of the organic extract fraction exhibited the characteristics of a mixed inhibitor. Bound phenolic‐n‐butanol fraction (IC50 = 98.39 ± 0.89 µg mL−1) had the strongest ability to scavenge the 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH). Additionally, the starch hydrolysis degree of n‐butanol extraction naked oat phenolic compound was significantly lower than other fractions in vitro. The integrated results suggested that OPC could be considered as potential healthy factor to control postprandial blood glucose, and the mechanism maybe via anti‐digestion, antioxidation and interaction with diabetes‐related starch.

Inhibition of Digestive Enzymes and Antioxidant Activity of Extracts from Fruits of Cornus alba, Cornus sanguinea subsp. hungarica and Cornus florida–A Comparative Study

The fruits of some Cornus species (dogwoods) are used in traditional medicine and considered potential anti-diabetic and hypolipemic agents. The aim of the study was to determine the ability of extracts from Cornus alba (CA), Cornus florida (CF), and Cornus sanguinea (CS) to inhibit digestive enzymes namely α-amylase, pancreatic lipase, and α-glucosidase, as well as isolation of compounds from plant material with the strongest effect. In addition, the phytochemical profile and antioxidant activity of extracts from three dogwoods were compared with HPLC-DAD-MS/MS and DPPH scavenging assay, respectively. Among the aqueous-ethanolic extracts, the activity of α-amylase was the most strongly inhibited by the fruit extract of CA (IC50 = 115.20 ± 14.31 μg/mL) and the activity of α-glucosidase by the fruit of CF (IC50 = 38.87 ± 2.65 μg/mL). Some constituents of CA fruit extract, such as coumaroylquinic acid, kaempferol, and hydroxytyrosol derivatives, were isolated. Among the three species of dogwood studied, the greatest biological potential was demonstrated by CA extracts, which are sources of phenolic acids and flavonoid compounds. In contrast, iridoid compounds or flavonoid glycosides found in fruits of CF or CS extracts do not play a significant role in inhibiting digestive enzymes but exert antioxidant activity.

Polyphenol-enriched fraction and the compounds isolated from Garcinia indica fruits ameliorate obesity through suppression of digestive enzymes and oxidative stress

Background: The growing incidence of obesity has attracted the concern of researchers to look for effective interventions for its management. Garcinia indica is a widely known ethnomedicine used to treat gastritis, diabetes, and metabolic disorders. Recently, there has been a surge in the use of G. indica fruits in weight loss preparations. Objective: To explore the anti-obesity effect of polyphenol-enriched fraction and the compounds isolated from G. indica fruits through the inhibition of key metabolizing enzymes and oxidative stress. Materials and Methods: Fruits of G. indica were extracted with methanol that was subjected to liquid–liquid extraction to yield ethyl acetate fraction (FGIEF), chloroform, butanol, and aqueous fractions. The extract and the fractions were screened for the total polyphenols content (TPC), total flavonoids content (TFC), pancreatic lipase (PL) and α-amylase inhibition, and antioxidant activity. The effect of FGIEF on the viability of 3T3-L1 preadipocytes using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay was assessed. FGIEF was subjected to normal-phase medium-pressure liquid chromatography (MPLC) to isolate compounds 1–3. Docking studies of representative polyphenols and the isolated compounds 1–3 with PL were undertaken to derive supporting evidence. Results: Among all the fractions, FGIEF was found to have the highest TPC (375.6 ± 4.5 gallic acid equivalent mg/g) and TFC (237.2 ± 6.2 quercetin equivalent mg/g). The extract and fractions showed concentration-dependent digestive enzyme inhibition and antioxidant effect. FGIEF inhibited PL and α-amylase (IC50values 257.3 ± 3.7 and 349.7 ± 5.8 μg/mL, respectively). FGIEF did not induce any cell death up to 800 μg/mL. MPLC of FGIEF led to the isolation of luteolin (1), napthyldioxolol (2), and oleantrienoic acid glucoside (3). Preferential inhibition by polyphenols compared to other compounds was notable in the docking studies. Conclusion: The study suggests that the fruits of G. indica exhibit anti-obesity effect through the inhibition of digestive enzymes that can be mainly attributed to the presence of polyphenols.

Acute effects of apple extracts with different polyphenol compositions on glucose transport in human intestinal cell line Caco-2/TC7

AbstractDiets with a high-glycaemic load may increase the risk of type 2 diabetes. Food and beverages containing large amounts of highly bioaccessible starch and sugars induce pronounced postprandial blood glucose concentrations. Chronic exposure to sharp blood glucose peaks can lead to oxidative stress and pancreatic beta-cell dysfunction. Fruit polyphenols may help to limit the glucose excursion following a high-carbohydrate meal.Our previous research showed that 1.8 g polyphenol-rich apple extract (AE) mixed into a drink consumed before a high starch + sucrose meal, inhibited the incremental area under the curve of plasma glucose during the early absorption-driven postprandial phase (0–30 min) by 52% relative to a placebo drink and meal. Our latest dose-response trial showed that the glycaemic response to starch and sucrose was modified by 0.9 g AE. Possible mechanisms include activity inhibition of carbohydrate digestive enzymes and/or glucose absorption (SGLT1/GLUT2 transport). The AE is uniquely high in phlorizin (10.6%) – a strong inhibitor of SGLT1. However, evidence shows that other apple polyphenols may also inhibit SGLT1.The primary aim of our work was to explore the effect of different mixtures of apple polyphenols on gut transporters involved in glucose uptake. Acute dose-response effect of the AE and three fractions of AE (20%, 40% and 80% methanol elution during fractionation) on total glucose transport were investigated in Caco-2/TC7 cells. Uptake media (10min) contained, except for controls, increasing concentrations of AE/fractions (0–4.5mg/ml) incorporating the physiological range estimated to be present in the small intestine after ingestion of clinical trial test drinks. Glucose transport under sodium-dependent conditions was determined by radiochemical detection of Glucose D-[14C(U)] and Glucose L-[1-14C].A 47% decrease in total glucose uptake was observed with 1.12mg/ml AE (i.e. clinical trial highest physiological dose) v control (P = 0.03). Dose-response experiments showed IC50were: 1.29 mg/ml, 0.31 mg/ml and 0.88 mg/ml for AE (mg/g: 79 phlorizin; 26 epicatechin; 4 quercetin), 80% fraction (mg/g: 101 phlorizin; 26 epicatechin; 38 quercetin), 40% fraction (mg/g: 83 phlorizin; 20 epicatechin; 7 quercetin), respectively. The 20% fraction (mg/g: 4 phlorizin; 12 epicatechin; 2 quercetin) had no effect on glucose transport.We have gained greater understanding of a potential mechanism for the anti-hyperglycaemic properties of apple polyphenols, supporting potential applications of the AE in functional foods/beverages. Our in vitro data suggest that a combination of higher amounts of phlorizin and quercetin may be important to maximise intestinal glucose uptake inhibition.

Antidiabetic potential of Bauhinia forficata Link leaves: a non-cytotoxic source of lipase and glycoside hydrolases inhibitors and molecules with antioxidant and antiglycation properties

Bauhinia forficata Link., a cerrado native plant, is used as a complementary treatment for Type 2 Diabetes Mellitus (T2DM). Several studies involving this plant have shown that it has prominent potential to combat hyperglycemia and oxidative stress. Our objective was suggest the phytochemical constitution of fractions of ethanol extract of B. forficata leaves using HPLC-ESI-MS/MS, and evaluates their activities in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant and anti-glycation capacities. In addition, we evaluated the cytotoxic effects of these fractions using rodents macrophages and erythrocytes. The ETOAC e ButOH fractions showed high polyphenols concentrations, having been determined 11 flavonoids, including the kaempferitrin, the phytomarker of B. forficata Link. In addition, all fractions presented higher antioxidant and antiglycation activities and prominent capacities to digestive enzymes inhibition. On the other hand, in the cellular assays, none fractions showed cytotoxic and hemolytic effects, able to combat the ROS production in macrophages. Thus, this study presented new results on the biological activities of this plant, contributing to the understanding of the action and effectiveness of its use in the management of diabetes mellitus and its complications.

Chemoprotective and antiobesity effects of tocols from seed oil of Maqui-berry: Their antioxidative and digestive enzyme inhibition potential

Maqui-berry (Aristotelia chilensis) is the emerging Chilean superfruit with high nutraceutical value. Until now, the research on this commodity was focused on the formulations enriched with polyphenols from the pulp. Herein, contents of tocols were compared in the seed oil of Maqui-berry obtained through three different extraction methods followed by determining their antioxidative and enzyme inhibitions in-vitro. Firstly, oilseed was extracted with n-hexane (Soxhlet method), chloroform/methanol/water (Bligh and Dyer method) and pressing (industrial). These samples were used to access their effects against DPPH, HORAC, ORAC, FRAP, Lipid-peroxidation (TBARS), α-amylase, α-glucosidase, and pancreatic lipase. All the isomers of tocopherol and tocotrienol were identified, and β-sitosterol was the only sterol found in higher amounts than other vegetable oils. The Bligh and Dyer method could lead to the highest antioxidative capacity compared to Soxhlet and press methods likely because the latter have a higher amount of tocopherols. Further, seed oil from Maqui berry and their tocols (α, β, γ, δ-tocopherols, tocotrienols, and β-sitosterol) warrant clinical investigation for their antioxidative and antiobesity potential. Taken together, these findings provide relevant and suitable conditions for the industrial processing of Maqui-berry.

Dual Insecticidal Effects of Adenanthera pavonina Kunitz-Type Inhibitor on Plodia interpunctella is Mediated by Digestive Enzymes Inhibition and Chitin-Binding Properties.

The Indianmeal moth, Plodia interpunctella, is one of the most damaging pests of stored products. We investigated the insecticidal properties of ApKTI, a Kunitz trypsin inhibitor from Adenanthera pavonina seeds, against P. interpunctella larvae through bioassays with artificial diet. ApKTI-fed larvae showed reduction of up to 88% on larval weight and 75% in survival. Trypsin enzymes extracted from P. interpunctella larvae were inhibited by ApKTI, which also demonstrated capacity to bind to chitin. Kinetic studies revealed a non-competitive inhibition mechanism of ApKTI for trypsin, which were further corroborated by molecular docking studies. Furthermore, we have demonstrated that ApKTI exhibits a hydrophobic pocket near the reactive site loop probably involved in chitin interactions. Taken together, these data suggested that the insecticidal activity of ApKTI for P. interpunctella larvae involves a dual and promiscuous mechanisms biding to two completely different targets. Both processes might impair the P. interpunctella larval digestive process, leading to larvae death before reaching the pupal stage. Further studies are encouraged using ApKTI as a biotechnological tool to control insect pests in field conditions.

Chemical characterization and bioactivities of polysaccharides from Apocynum venetum leaves extracted by different solvents

Apocynum venetum has a long history as a Chinese traditional tea. As one of the major components, polysaccharides from Apocynum venetum leaves were extracted with acid (HCl), distilled water and alkaline (NaOH) to study the effect of the extraction solvents on their chemical composition and biological activities in this work. Monosaccharide composition revealed that polysaccharides from acidic and distilled water extraction were pectic polysaccharides, while those from alkaline extraction consisted of pectin and hemicellulose. Chemical analysis and FT-IR spectra indicated the co-extraction of protein and polyphenol contents in alkaline extracted polysaccharides, which exhibited strongest antioxidant and digestive enzyme inhibition activities. The antioxidant capacities were 185.26–286.30 mg TE/g for DPPH radical scavenging, 409.06–502.00 mg TE/g for ABTS radical scavenging, and 152.12–260.70 mg TE/g sample for reducing power assay, respectively. The lowest IC50 for α-glucosidase and lipase inhibition activities were 16.75 μg/mL and 820 μg/mL, respectively. Further purification of alkaline extracts was carried out and characterized. The results showed that acid hydrolysis could successfully reduce polyphenol and protein contents, and purified polysaccharides showed even higher antioxidant activities and α-glucosidase inhibition activity. These results provide a scientific support for functional application and extraction of polysaccharides from Apocynum venetum leaves.

Iso-Mukaadial Acetate from Warburgia salutaris Enhances Glucose Uptake in the L6 Rat Myoblast Cell Line.

Diabetes mellitus (DM) is a chronic metabolic disorder which has become a major risk to the health of humankind, as its global prevalence is increasing rapidly. Currently available treatment options in modern medicine have several adverse effects. Thus, there is an urgent need to develop alternative cost-effective, safe, and active treatments for diabetes. In this regard, medicinal plants provide the best option for new therapeutic remedies desired to be effective and safe. Recently, we focused our attention on drimane sesquiterpenes as potential sources of antimalarial and antidiabetic agents. In this study, iso-mukaadial acetate (Iso) (1), a drimane-type sesquiterpenoid from the ground stem bark of Warburgia salutaris, was investigated for glucose uptake enhancement in the L6 rat myoblast cell line. In vitro assays with L6 skeletal muscle cells were used to test for cytotoxicity, glucose utilisation, and western blot analysis. Additionally, the inhibition of carbohydrate digestive enzymes and 1,1-diphenyl-2- picrylhydrazyl (DPPH) scavenging activity were analysed in vitro. The cell viability effect of iso-mukaadial acetate was the highest at 3 µg/mL with a percentage of 98.4. Iso-mukaadial acetate also significantly and dose-dependently increased glucose utilisation up to 215.18% (12.5 µg/mL). The increase in glucose utilisation was accompanied by enhanced 5’ adenosine monophosphate-activated protein kinase (AMPK)and protein kinase B (AKT) in dose-dependent manner. Furthermore, iso-mukaadial acetate dose-dependently inhibited the enzymes α-amylase and α-glucosidase. Scavenging activity against DPPH was displayed by iso-mukaadial acetate in a concentration-dependent manner. The findings indicate the apparent therapeutic efficacy of iso-mukaadial acetate isolated from W. salutaris as a potential new antidiabetic agent.

Comparative analysis of isoflavone aglycones using microwave-assisted acid hydrolysis from soybean organs at different growth times and screening for their digestive enzyme inhibition and antioxidant properties

The objectives of this research were to demonstrate the changes in isoflavone-aglycones, total phenolics, and biological properties (digestive enzyme inhibition; antioxidant) from six organs including leaves, leafstalks, roots, stems, seeds, and pods at different growth times of soybean plant. Three isoflavone-aglycones in microwave-assisted acid hydrolysis extracts were elucidated using UHPLC-ESI-Q-TOF-MS/MS and their contents exhibited remarkable differences in leaves (245.93–2239.33 μg/g), roots (854.96–4425.34 μg/g), and seeds (ND–2339.62 μg/g). Specifically, the collected samples on 15-Oct (leaves: 2239.33; seeds: 2339.62 μg/g) and 31-Aug (roots: 4425.34 μg/g) showed the highest isoflavone-aglycones, and daidzein was observed the most abundant component, comprising approximately 70%. Moreover, the inhibitions against α-glucosidase and α-amylase displayed the predominant effects in roots (89;91%) and leaves (81;85%) of samples on 31-Aug and 15-Oct at 300 μg/ml. The antioxidant activities on ABTS, DPPH, and hydroxyl radicals increased considerably with the increases of growth times in leaves and seeds, especially, ABTS showed the highest scavenging abilities: leaves (15-Oct;83%) > roots (31-Aug;75%) > seeds (15-Oct;68%). Therefore, our results suggest that soybean leaves, roots and seeds may be considered as excellent natural sources for nutraceuticals.

Phenolic content, acute toxicity of Ajuga iva extracts and assessment of their antioxidant and carbohydrate digestive enzyme inhibitory effects

The management of blood glucose level is the hallmark in the treatment of type 2 diabetes, and this may be achieved through the inhibition of the digestive enzymes involved in carbohydrate metabolism. The aim of this work is the investigation of phenolic compounds content, antioxidant activity and for the first time, the in vitro anti-hyperglycemic potential of aerial part of Ajuga iva Schreber extracts through the inhibition of digestive enzymes (α-amylase and α-glucosidase), responsible of the digestion of poly and oligosaccharides. Test for total phenolic content showed that the methanol extract has the highest polyphenolic and flavonoid concentrations with (65.3 mg GAEs/g extract and 132.6 mg REs/g extract). The methanol extract has also exhibited the higher antioxidant activity compared to the aqueous extract in different tests with (IC50=0.187±0.016 mg/mL; 62.19±0.45 mg TE/g extract; 89.12±0.23 mg AAE/g extract) in DPPH, ABTS and FRAP tests, respectively. Ajuga iva extracts exhibited a remarkable inhibitory activity against key digestive enzymes linked to type 2 diabetes, with a more potent inhibitory effect against α-glucosidase and a considerable inhibition against α-amylase. The results indicated also that the tested extracts are non-toxic with an LD50 higher than 2 g/kg in female Swiss mice. These results suggested that the phenolic compounds in A. iva extracts maybe behind the antioxidant and antidiabetic activities. However, further investigations regarding the bioactive compounds and their mechanisms of action are required for developing new natural drugs against diabetes-related hyperglycemia.

The effect of olive leaf extract on digestive enzyme inhibition and insulin production in streptozotocin-induced diabetic rats

Olive leaf has natural bioactive compounds, mainly oleuropein, that are widely considered to have potentially beneficial effects on health. This study aimed to evaluate the effects of olive leaf extract (OLE) on the inhibition of carbohydrate digestive enzymes, and immunohistochemical study of insulin in the pancreas of in vivo streptozotocin-induced diabetic rats. Blood glucose levels, insulin, glycated hemoglobin (HbA1c), α-amylase and α-glucosidase activities, and an immunohistochemical study were performed at the end of the experiment. In the OLE treated group, blood glucose levels and HbA1c significantly decreased while insulin levels increased. Besides this, OLE treated group showed remarkable inhibitory activities on α-amylase and α-glucosidase compared with the Acarbose treated group. It was observed that OLE exhibited partial positive immunoreaction for insulin in β-cells through immunohistochemical analysis. Considering that OLE is more tolerable for digestion system compared to acarbose, it may be a better fitoformulation for antidiabetic medications. OLE could offer an additional beneficial effect for the treatment of diabetes.

Insight into flavonoid structure for mammalian α‐amylase and α‐glucosidase inhibition to control starch digestion rate

In this study we investigated the structural specificity of flavonoids for starch digestive enzyme inhibition to modulate glucose release from glycemic carbohydrate digestion. Using three different flavonoids [eriodictyol, luteolin, and quercetin], chosen based on the degree of hydroxylation and planarity of the C‐ring, structural specificities were found for selectively inhibiting α‐amylase and α‐glucosidases, resulting in different inhibition constants (Ki) and mechanisms. The double bond between C2 and C3 on the C‐ring of flavonoids was particularly important for α‐amylase inhibition, which leads to a π‐stacking interaction between flavonoids and α‐amylase, while the hydroxyl group at C3 of the C‐ring played a key role in inhibiting α‐glucosidases. These structural specificities of flavonoids toward starch degrading enzymes are likely the result of different protein structures of α‐amylase and α‐glucosidases, as they belong to different families, GH13 and GH31. Our findings provide insights into structure‐function aspects of flavonoids in controlling starch digestion rate.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Antioxidative dolabellanes and dolastanes from brown seaweed Padina tetrastromatica as dual inhibitors of starch digestive enzymes

New dolabellanes {6-methoxy-dolabella-8(17),12-diene-10β,18-diol (1), 3-methoxy-dolabella-12(18)-ene-4β-ol (2), 3-methoxy-dolabella-10,18(19)-diene-5α,8β-diol (3)} and dolastanes {2,7-dimethoxy-14α-hydroxy-dolasta-1(15),9-diene (4) and 4,7-dimethoxy-9β,14α-dihydroxy-dolasta-1-ene (5)} were identified from brown seaweed Padina tetrastromatica (family Dictyotaceae), collected from the southeast coast of India. Compounds 1–3 were found to possess dolabellane skeleton with [9.3.0] cyclotetradecane framework whereas, 4–5 were composed of tricyclic diterpenes with linear arrangement of six-seven-five fused alicyclic rings. Compounds 3 and 5 registered greater antioxidative activities (IC50 ≤0.63 mg/mL) than other analogues (IC50 ≥0.65 mg/mL), whereas their attenuating potentials against carbolytics α-amylase and α-glucosidase (IC50 ∼0.12–0.14 mg/mL) were comparable with those displayed by acarbose (IC50 0.14-0.12 mg/mL). Bioactive potentials of titled compounds were assessed by electronic and lipophilic parameters. The lesser binding energies of 3 (−9.71 kcal/mol) and 5 (−8.59 kcal/mol) through molecular docking demonstrated their effective hydrogen bonding interactions with α-amylase. Thus, dolabellanes and dolastanes might be used as anti-diabetic and antioxidant leads to reduce the risk of hyperglycaemia.

First report of antioxidative abeo-oleanenes from red seaweed Gracilaria salicornia as dual inhibitors of starch digestive enzymes

Carbolytic enzyme-associated cascades have been considered as potential curative target in attenuating diabetic mellitus pathogenesis. Two oleanene class of triterpenoids characterised as 24(4 → 23), 27(8 → 26), 30(20 → 29)-tris-abeo-olean-(12-oxo)-1,15,22-triene-methyl hept-5-enoate (1) and 24(4 → 23)-abeo-olean-(12-oxo)-3,5-diene-deconoate (2) with potential inhibitory activities against the starch digestive enzymes α-glucosidase and α-amylase, were purified from the organic extract of intertidal red seaweed Gracilaria salicornia (family Gracilariaceae). Structural interpretation of compounds was carried out by detailed spectroscopic analysis, and their antioxidant/anti-diabetic potentials were assessed. Inhibitory potential of abeo-oleanene derivative (2) towards the starch digestive enzymes, α-glucosidase (IC50 0.29 mM) and α-amylase (IC50 0.32 mM) were greater than those displayed by its abeo-oleanene chemotype 1 (IC50 0.34–0.40 mM). The molecular modelling studies were performed to designate the α-amylase and α-glucosidase inhibitory mechanism of oleanene analogues, and the comparison of docking parameters suggested that compound 2 exhibited least binding energy of −10.04 and −9.84 kcal mol−1 towards α-amylase and α-glucosidase respectively, and those results were corroborated with its greater inhibition potential against carbolytic enzymes. These results demonstrated that abeo-oleanene derivative (2) might constitute prospective anti-hyperglycaemic pharmaceutical candidate to moderate the likelihood of type-II diabetes.

Design of low glycemic response foods using polyphenols from seaweed

Several aspects of foods affect starch digestion and glycemic response, including food’s physical/chemical structure and the presence of anti-enzymatic compounds. The complex relationship between food properties, metabolism and diseases implies that designing foods with a consistent lower glycemic response turn challenging. Edible seaweeds are rich in several bioactive compounds -particularly polyphenols-, which can be used to develop new low glycemic response foods. This paper reviews what is known about functional ingredients found in seaweeds that may help to design lower glycemic response foods through mainly the inhibition of digestive enzymes related with the breakdown of glycemic carbohydrates. A global viewpoint is exposed, covering aspects related with seaweed’s polyphenols composition and application of such compounds to design new products.