In Vitro Potential of Ascophyllum nodosum Phenolic Antioxidant-Mediated α-Glucosidase and α-Amylase Inhibition

ABSTRACT: Ascophyllum nodosum is a brown seaweed that grows abundantly in the Northeast coastal region. In this study, the potential of A. nodosum for type 2 diabetes management through antioxidant-mediated α-glucosidase and α-amylase inhibition was investigated. After the initial screening of 4 locally harvested seaweeds, A. nodosum was chosen for its highest phenolic content and was subjected to water extraction. Among extraction ratios of 50 g to 100 to 1000 mL at room temperature, 50 g/400 mL yielded the highest phenolic content of 4.5 mg/g wet weight. For evaluation of extraction temperature ranging from 20 to 80 °C, 50 g/400 mL was chosen as a minimum amount of extractant. Among temperatures studied, extraction at 80 °C resulted in the highest total phenolic contents (4.2 mg/g wet weight). All extracts had similar levels of antioxidant activity in the range of 60% to 70% in terms of 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. The 80 °C extract had the highest α-glucosidase and α-amylase inhibitory activity with IC₅₀ of 0.24 and 1.34 μg phenolics, respectively, compared to the IC₅₀ of acarbose, reference inhibitor, being 0.37 and 0.68 μg. The results show that fresh A. nodosum has strong α-glucosidase and mild α-amylase inhibitory activities that correlated with phenolic contents. This study suggests a nutraceutical potential of A. nodosum based on phytochemical antioxidant and antihyperglycemia activities.     

Inhibition of the in vitro activities of α-amylase, α-glucosidase and pancreatic lipase by yellow field pea (Pisum sativum L.) protein hydrolysates

The aim of this work was to produce yellow field pea protein-derived peptides as inhibitors of α-amylase, α-glucosidase and pancreatic lipase activities. A pea protein concentrate was hydrolysed with alcalase, chymotrypsin, pepsin or trypsin and the hydrolysates separated into different fractions (<1, 1–3, 3–5, 5–10 kDa) by membrane ultrafiltration. Peptide sequence analysis showed that the alcalase hydrolysate had higher levels of di- and tripeptides when compared with the chymotrypsin, pepsin and trypsin hydrolysates. The peptide fractions inhibited α-amylase and α-glucosidase activities at levels that were similar to the unfractionated hydrolysates. The peptides were more active against α-amylase (inhibition at μg level) than α-glucosidase (mg level). In contrast, the fractionated peptides had reduced ability (IC₅₀ >4.2 mg mL⁻¹) when compared with the unfractionated hydrolysate (IC₅₀ <4.2 mg mL⁻¹) to inhibit lipase activity. Enzyme kinetic studies revealed that the peptides reduced α-amylase activity through competitive inhibition. However, inhibition of α-glucosidase activity was non-competitive.     

Metabolite profiling and inhibitory properties of leaf extracts of Ficus benjamina towards α-glucosidase and α-amylase

The use of antioxidant-rich medicinal plants having the potential to reduce oxidative stress and postprandial hyperglycemic pressure is one of the most promising option for the management of diabetes. This study presents information on metabolite profiling and in vitro anti-diabetic effects of leaf extracts of Ficus benjamina. The DPPH (2, 2-diphenyl-1-picrylhydrazyl radicals) assay was performed to determine the in vitro antioxidant potential of the plant extracts. The anti-diabetic effects were investigated by evaluating inhibitory properties of F. benjamina leaf extracts towards carbohydrate hydrolyzing enzymes, i.e., α-glucosidase and α-amylase, whereas ¹H NMR and UHPLC-QTOF-MS/MS analytical methods were employed for metabolite profiling of F. benjamina leaf extracts. Among 40, 60, 80, and 100% ethanolic leaf extracts of F. benjamina, 80% ethanolic extract exhibited the highest antioxidant activity based upon its DPPH radical scavenging ability (IC₅₀ value: 63.71 ± 2.66 µg/mL). The 80% ethanolic leaf extract of F. benjamina also proved to be the most efficient α-glucosidase and α-amylase inhibitor with IC₅₀ values of 9.65 ± 1.04 µg/mL and 13.08 ± 1.06 µg/mL, respectively; these values were even better than acarbose with α-glucosidase inhibition activity (IC₅₀ = 116.01 ± 3.83 µg/mL) and α-amylase inhibition activity (IC₅₀ = 152.66 ± 7.32 µg/mL). Moreover, a total of 31 metabolites were identified in F. benjamina leaf extract, which may have the potential to contribute to its antioxidant and inhibitory properties against carbohydrate hydrolyzing enzymes. The findings of this study depict F. benjamina leaf extracts as a promising α-glucosidase and α-amylase inhibitor, and therefore, can be utilized for the development of anti-diabetic functional diets/nutra-pharmaceuticals.     

The inhibitory effects of ethanol extracts from sorghum,foxtail millet and proso millet on α-glucosidase and α-amylase activities

Cereal crops have recently experienced increased interest due to their potential health benefits. It has been suggested that the intake of whole grain foods is beneficial to the prevention and management of diabetes mellitus. In this study, we investigated the inhibitory effect of 70% EtOH extracts from different cultivars of sorghum, foxtail millet and proso millet on α-glucosidase and α-amylase. Among the six sorghum cultivars, Mongdang-susu(SS-1), Me-susu(SS-2), Susongsaengi-susu(SS-3) and Sikyung-susu(SS-4) extracts exhibited higher inhibitory activities against α-glucosidase (IC₅₀ = 1.1–1.4 μg/ml) than acarbose, reference inhibitor (IC₅₀ = 2.1 μg/ml). In addition, these extracts strongly inhibited degradation of starch by pancreatic and salivary α-amylase, whereas extracts from foxtail and proso millets exhibited no visible or detectible inhibitory effect on α-amylase or on α-glucosidase activity. These in vitro studies indicate the potential of sorghum in the development of effective anti-diabetic agents.     

Effects of impregnate temperature on extraction of caffeoylquinic acid derivatives from Moringa oleifera leaves and evaluation of inhibitory activity on digestive enzyme,antioxidant, anti-proliferative and antibacterial activities of the extract

In an ultrasonic bath and for 30 min in the presence of water as extraction solvent in a ratio of 1:10 (g/mL), effect of extraction temperature on extraction of caffeoylquinic acids (CQAs) from Moringa oleifera leaves (MOL) was investigated. Gradually increasing in extraction temperature caused a growing in mono-CQA and declining in 3,5-diCQA. The extract obtained at 80 °C showed the highest antioxidant capacity, and IC₅₀ values for scavenging activities on DPPH radicals and ABTS radicals were 56.9 and 53.6 µg/mL, respectively. Compared with α-glucosidase and α-amylase, the extract showed the highest inhibition on pancreatic lipase (IC₅₀ of 0.073 mg/mL). Increasing the extraction temperature improved cytotoxicity of the extract on cancer cell lines of HeLa and HepG2. Compared with gram-negative Escherichia coli and Salmonella typhimurium, all the extracts showed higher inhibition on the growth of gram-positive Bacillus cereus and Staphylococcus aureus. Our results suggested that use of higher extraction temperature (80 °C) improved the biological activity of MOL extract.     

Inhibitory activities of extracts from Cleistocalyx operculatus flower buds on pancreatic lipase and α-amylase

In this work, we investigated the inhibitory activities of aqueous extract (Eaq), 30, 60, and 95?% ethanol extracts (E₃et, E₆et, and E₉et), petroleum ether extract (Epe), ethyl acetate extract (Eae), and 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) from Cleistocalyx operculatus flower buds on pancreatic lipase and α-amylase, which were closely related to body weight and obesity. The inhibition effect of various extracts was determined by the Lineweaver–Burk plots. The results showed that the IC₅₀ values of DMC, Epe, Eae, and E₉et against pancreatic lipase were 101.5?μM, 38.65, 76.62, and 109.76?μg/ml, respectively, which were much lower than that of E₃et and E₆et. Eaq, E₃et, E₆et, and DMC strongly inhibiting the pancreatic α-amylase, with IC₅₀ values of 73.10, 165.93, 231.23?μg/ml, and 69.35?μM, respectively. Furthermore, the kinetic analysis suggested that the inhibition mode of crude extract against pancreatic lipase was noncompetitive, while that against pancreatic α-amylase was competitive. The content of DMC and total polyphenols in each extract were determined by HPLC and spectrophotometric method, respectively. It was interestingly found that the DMC content had profound influence on pancreatic lipase activity, and the total polyphenols content significantly affected the pancreatic α-amylase activity. The findings in this work suggested that extracts from C. operculatus flower buds possess potent inhibitory activity against pancreatic lipase and α-amylase, and provided some new ideas for the prevention and treatment for obesity.     

Effect of a commercially-available algal phlorotannins extract on digestive enzymes and carbohydrate absorption in vivo

The ability of naturally occurring polyphenols and phlorotannins (PHTs) from some species of brown seaweeds to inhibit α-amylase and α-glucosidase enzymes in vitro has already been demonstrated. This study aimed at validating the efficacy of a new food ingredient extracted from Ascophyllum nodosum and Fucus vesiculosus PHTs at inhibiting digestive enzymes in vitro and slowing carbohydrate absorption in vivo. In vitro, the PHT extract completely inhibited in a dose-dependent fashion α-amylase and α-glucosidase with very low IC₅₀ values compared to other plant polyphenols. In animals, the PHT extract was able to reduce the normal increase in postprandial blood glucose seen 30 min after a meal by 90% (p < 0.05), and consecutively reduce peak insulin secretion by 40%. These results demonstrate the potency of this specific PHT extract to beneficially modulate carbohydrate digestion and assimilation, in a way that would be suitable for use in foods and dietary supplement formulations.     

Major triterpenes,cycloeucalenone and 31-norcyclolaudenone as inhibitors against both α-glucosidase and α-amylase in banana peel

The inhibitory activities of banana peel extract against carbohydrate digestive enzymes were investigated. Cycloeucalenone and 31-norcyclolaudenone were obtained by bioassay-guided fractionation as effective inhibitors of α-glucosidase and α-amylase. The structure–activity relationships of four triterpenes isolated from banana peel, cycloeucalenone, 31-norcyclolaudenone and cycloeucalenol and its isomer were investigated. The IC₅₀ values of cycloeucalenone and 31-norcyclolaudenone against α-glucosidase were 31.83 ± 2.46 μm and 38.85 ± 1.54 μm , respectively, and their IC₅₀ values against α-amylase were 20.33 ± 0.59 μm and 27.63 ± 0.83 μm , respectively. In contrast, cycloeucalenol and its isomer had insufficient inhibitory activity against either enzyme. The primary active sites of cycloeucalenone and 31-norcyclolaudenone are the carbonyl group at C-3 and the double bond in the side chain. Cycloeucalenone induced a parabolic mixed-type inhibition with a K_i value of 73.86 μm in the α-glucosidase inhibitory assay. This study provides new evidence for the potential use of banana peel triterpenes as antidiabetic agents.     

Inhibitory potential of trilobatin from Lithocarpus polystachyus Rehd against α-glucosidase and α-amylase linked to type 2 diabetes

The chemical structure of the sweet compound from Lithocarpuspolystachyus Rehd was identified as trilobatin on the basis of HPLC, EIS-MS and NMR analyses. The inhibitory activities of trilobatin against α-glucosidase and α-amylase were evaluated, and the inhibition mechanism was analysed with Lineweaver–Burk plots. Also the antioxidant activity evaluation of trilobatin was conducted by DPPH radical scavenging assay. Comparing with acarbose, trilobatin showed a strong inhibitory activity against α-glucosidase and a moderate inhibitory activity against α-amylase. The Lineweaver–Burk plots analysis elucidated that trilobatin inhibited the enzyme non-competitively. DPPH scavenging activity of trilobatin (IC₅₀ = 0.57 mg/ml) was higher than rutin (IC₅₀ = 0.72 mg/ml), which indicated that trilobatin had a moderate antioxidant potential. These results suggest that trilobatin is a potential effective α-glucosidase inhibitor for management of postprandial hyperglycemia with less side effect, and provide strong rationale for further animal and clinical studies.     

Inhibitory effect of polyphenol-rich extracts of jute leaf (Corchorus olitorius) on key enzyme linked to type 2 diabetes (α-amylase and α-glucosidase) and hypertension (angiotensin I converting) in vitro

Corchorus olitorius leaf is consumed in various parts of the world as leafy vegetable and folk remedy for the management of some degenerative diseases with dearth of information on its biochemical rationale. Therefore, this study sought to characterize the inhibitory action of polyphenol-rich extracts (free and bound) of C. olitorius on α-amylase, α-glucosidase and angiotensin I converting enzyme (ACE), as well as to identify the phenolic compound responsible for these activities. Our findings revealed that the extracts inhibited α-amylase and α-glucosidase (12.5–50.0 μg/mL), and ACE (10.0–50.0 μg/mL) in dose-dependently with free extracts having significantly (P < 0.05) higher α-amylase (17.5 μg/mL), α-glucosidase (11.4 μg/mL) and ACE (15.7 μg/mL) inhibitory activities as revealed by the IC₅₀. Reversed-phase HPLC analysis of the extracts revealed chlorogenic acid (7.5 mg/100 g) and isorhamnetin (51.1 mg/100 g) as the main phenolics in the free extract and caffeic acid (58.1 mg/100 g) in the bound extract. Therefore, the enzyme inhibitory activity of C. olitorius extracts may be attributed to the presence of caffeic acid, chlorogenic acid and isorhamnetin, thus justifying its use in folklore for the management of diabetes and hypertension.     

Bioactive compounds extracted from Gamtae (Ecklonia cava) by using enzymatic hydrolysis, a potent α-glucosidase and α-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice

This study was designed to investigate whether the brown alga gamtae (Ecklonia cava) may inhibit α-glucosidase and α-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. For that purpose, we prepared an enzymatic hydrolysate from gamtae (EHG) by using the carbohydrase, Celluclast. EHG evidenced prominent inhibitory effect against α-glucosidase and α-amylase. The IC₅₀ values of EHG against α-glucosidase and α-amylase were 0.62 and 0.59 mg/mL, respectively, which evidenced the higher activities than that of acarbose. EHG did not exert any cytotoxic effect in human umbilical vein endothelial cells (HUVECs) at various concentrations (from 0.25 to 2 mg/mL). The increase of postprandial blood glucose levels were significantly suppressed in the EHG administered group than those in the streptozotocin-induced diabetic or normal mice. Moreover, the area under curve (AUC) was significantly reduced via EHG administration (6,102 vs. 10,425 mg·min/dL) in the diabetic mice as well as it delays absorption of dietary carbohydrates. These result indicated that EHG might be a potent inhibitor for α-glucosidase and α-amylase.     

Screening of Possible In Vitro Neuroprotective,Skin Care,Antihyperglycemic, and Antioxidative Effects of Anchusa undulata L. subsp. hybrida (Ten.) Coutinho from Turkey and Its Fatty Acid Profile

The aim of this work was to determine antioxidant capacities, neuroprotective, skin care, antidiabetic effects, and fatty acid composition of Anchusa undulata subsp. hybrida. The antioxidant activity was screened by four different test systems including total antioxidant, antiradical, reducing power, and metal chelating activities. Neuroprotective potential was determined by anticholinesterase inhibitor assay. Tyrosinase inhibitory activity was tested to detect skin care effect. Antidiabetic effects were evaluated with α-amylase and α-glucosidase inhibitory assays. Inhibitory activities on acetycholinesterase, butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase enzymes were observed as 2.238 and 1.239 μmol GALAEs/g, 0.339 mmol KAEs/g, 0.193, and 0.219 mmol ACEs/g extract, respectively. Amount of total phenolics and flavonoids were found as 80.34 μg GAEs/mg and 25.09 μg QEs/mg in the extract, respectively. Twenty-three fatty acids were found in the aerial parts, being oleic acid (24.30 g/100 g of total fatty acids) the most abundant, followed by linoleic (21.19 g/100 g of total fatty acids) and palmitic acids (17.50 g/100 g of total fatty acids).     

α-Glucosidase and α-amylase inhibitory activities of guava leaves

The 75% ethanol extract from guava (Psidium guajava Linn.) leaves was extracted further, in turn, with CH₂Cl₂, EtOAc and n-BuOH to afford four fractions, CH₂Cl₂-soluble, EtOAc-soluble, n-BuOH-soluble and residual extract fractions. Both the n-BuOH-soluble and EtOAc-soluble fractions showed high inhibitory activity against α-glucosidase and α-amylase. Seven pure flavonoid compounds, quercetin (1), kaempferol (2), guaijaverin (3), avicularin (4), myricetin (5), hyperin (6) and apigenin (7), were isolated (using enzyme assay-guide fractionation method) from the n-BuOH-soluble and EtOAc-soluble fractions. The structures of these pure compounds were determined on the basis of MS and NMR data and the activities of these compounds were evaluated. Compounds 1, 2 and 5 showed high inhibitory activities, with IC₅₀ values of 3.5 mM, 5.2 mM and 3.0 mM against sucrase, with IC₅₀ values of 4.8 mM, 5.6 mM and 4.1 mM against maltase and with IC₅₀ values of 4.8 mM, 5.3 mM and 4.3 mM against α-amylase, respectively. We found that myricetin showed the most powerful activity among these compounds with a 70% inhibition against sucrase at a concentration of 1.5 mg/ml. The hydroxyl group at the 3-position on the A-ring and a number of hydroxyl groups attached to the C-ring played important roles in the inhibition activity. There was an obvious synergistic effect (the mixing action of two compounds) against α-glucosidase, but against α-amylase this was not found. This is the first study of the active compositions of guava leaves and the biological activity of the active compositions against α-glucosidase and α-amylase.     

Flavonoids isolated from Syzygium aqueum leaf extract as potential antihyperglycaemic agents

Syzygium aqueum is a medicinal plant which is grown in tropical regions. In this study, the ethanolic extracts of S. aqueum leaf were investigated for its antihyperglycaemic activity. Our investigation revealed its effectiveness in inhibiting the carbohydrate hydrolysing enzymes, α-glucosidase (EC₅₀ = 11 μg/ml) and α-amylase (EC₅₀ = 8 μg/ml), at significant level than the commercial drug acarbose (EC₅₀ = 28 μg/ml, α-glucosidase; EC₅₀ = 12 μg/ml, α-amylase). In addition, the ethanolic leaf extracts were able to inhibit the key enzyme in the polyol pathway, aldose reductase (EC₅₀ = 0.03 μg/ml) and prevent the AGEs formation by 89%. Six flavonoid compounds, 4-hydroxybenzaldehyde (1), myricetin-3-O-rhamnoside (2), europetin-3-O-rhamnoside (3), phloretin (4), myrigalone-G (5) and myrigalone-B (6), were isolated from the ethanolic leaf extracts. Compounds (2) and (3) showed high inhibitory activities, with EC₅₀ values of 1.1 μM and 1.9 μM against α-glucosidase and EC₅₀ values of 1.9 μM and 2.3 μM against α-amylase, respectively. These findings provide a strong rationale to establish S. aqueum’s capability as an antihyperglycaemic agent.     

In vitro inhibitory effect of oriental melon (Cucumis melo L. var. makuwa Makino) seed on key enzyme linked to type 2 diabetes: Assessment of anti-diabetic potential of functional food

As the world’s population continues to increase, the agricultural discards of plant origin have attracted considerable attention for various purposes in the pharmaceutical and food industry. The objective of present study was to evaluate the potential of oriental melon (Cucumis melo L. var. makuwa Makino) seed for management of hyperglycaemia-linked to type 2 diabetes. Ethanol and hexane extracts from oriental melon seed were used to evaluate their inhibitory activities against α-glucosidase and α-amylase. Low phenolic-containing hexane extract exhibited much higher inhibitory activities against α-glucosidase and α-amylase than ethanol extract. The GC–MS result revealed that hexane extract constituted linoleic acid (29.6%), oleic acid (17.3%), and palmitic acid (6.5%). At high concentration, hexane extract exhibited strong inhibitory activities against α-glucosidase (35.3%) and α-amylase (61.8%). These in vitro studies indicated that hexane extract of oriental melon seed could be used as a potent alternative for controlling type 2 diabetes.     

The α-amylase and α-glucosidase inhibitory effects of Irish seaweed extracts

To date, numerous studies have reported on the antidiabetic properties of various plant extracts through inhibition of carbohydrate-hydrolysing enzymes. The objective of this research was to evaluate extracts of seaweeds for α-amylase and α-glucosidase inhibitory effects. Cold water and ethanol extracts of 15 seaweeds were initially screened and from this, five brown seaweed species were chosen. The cold water and ethanol extracts of Ascophyllum nodosum had the strongest α-amylase inhibitory effect with IC₅₀ values of 53.6 and 44.7 μg/ml, respectively. Moreover, the extracts of Fucus vesiculosus Linnaeus were found to be potent inhibitors of α-glucosidase with IC₅₀ values of 0.32 and 0.49 μg/ml. The observed effects were associated with the phenolic content and antioxidant activity of the extracts, and the concentrations used were below cytotoxic levels. Overall, our findings suggest that brown seaweed extracts may limit the release of simple sugars from the gut and thereby alleviate postprandial hyperglycaemia.     

玉蜀黍不同部位提取物对α-葡萄糖苷酶和α-淀粉酶抑制作用

目的:探究玉蜀黍不同部位(须、秸秆皮、秸秆芯)提取物对α-葡萄糖苷酶和α-淀粉酶活性抑制作用.方法:采用常规理化方法测定玉蜀黍不同部位中总黄酮、总皂苷、总多糖、总蛋白质提取物的含量,酶底物反应法和3,5-二硝基水杨酸比色法测定α-葡萄糖苷酶和α-淀粉酶抑制活性,考察不同pH、温度、时间对α-葡萄糖苷酶和α-淀粉酶活性影...     

Novel peptides derived from egg white protein inhibiting alpha-glucosidase

The aim of this study was to search and identify potential anti-diabetic peptides with α-glucosidase and α-amylase inhibitory activities. After the Alcalase hydrolysis, egg white protein hydrolysates were purified and identified by LC–MS–MS. Eight identified peptides were further synthesized by the Fmoc solid-phase synthesis. The anti-diabetic activities of these synthetic peptides were assessed using enzymatic inhibitory assays against the α-glucosidase and α-amylase. Among the eight peptides, peptide RVPSLM was discovered as a potential α-glucosidase inhibitor with an IC₅₀ value at 23.07 μmol L⁻¹. However, it did not exhibit a visible or detectable inhibitory efficiency on the α-amylase. These studies indicate the potential of using egg white protein hydrolysates as a functional food product with the anti-diabetic activity.     

Composition of native Australian herbs polyphenolic-rich fractions and in vitro inhibitory activities against key enzymes relevant to metabolic syndrome

Polyphenolic-rich fractions obtained from three native Australian herbs: Tasmannia pepper leaf, anise myrtle and lemon myrtle were characterised with regards to their composition, antioxidant capacities and inhibitory activities against α-glucosidase, pancreatic lipase and angiotensin I-converting enzyme, using in vitro models. Ellagic acid and derivatives were the dominant compounds of anise myrtle and lemon myrtle fractions, accompanied by flavonoids (catechin, myricetin, hesperetin, and quercetin). Tasmannia pepper leaf fraction comprised chlorogenic acid and quercetin derivatives, exhibited the highest oxygen radical absorbance capacity and effectively inhibited α-glucosidase (IC₅₀: 0.83 mg/ml) and pancreatic lipase (IC₅₀: 0.60 mg/ml). Anise myrtle and lemon myrtle fractions had pronounced α-glucosidase-inhibitory activities (IC₅₀: 0.30 and 0.13 mg/ml, respectively) and were less effective against lipase. Enzyme-inhibitory activities showed various levels of correlation with the levels of total phenolics and antioxidant capacities, indicating a specificity of individual phenolic compounds present in the isolated fractions to complex with proteins.     

Inhibitory effect on α-glucosidase by the fruits of Terminalia chebula Retz.

Mammalian α-glucosidase inhibitory activity by Terminalia chebula Retz. fruits was investigated. The aqueous methanolic extract was found to have potent rat intestinal maltase inhibitory activity, whereas neither intestinal sucrase nor isomaltase activity was inhibited by this extract. Using bioassay-guided separation, three active ellagitannins were identified as chebulanin (1), chebulagic acid (2) and chebulinic acid (3) and were shown to possess potent intestinal maltase inhibitory activity, with the IC₅₀ values of 690 μM, 97 μM and 36 μM, respectively. The intestinal maltase inhibitory activities of 2 and 3 were even higher than that of 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) (4, IC₅₀=140 μM), which is a known potent α-glucosidase inhibitor. Comparison of the activities of 1–4, 1,2,3-O-trigalloyl-β-d-glucose (5), neochebulagic acid (6) and corilagin (7) suggested that the positions of chebulloyl and galloyl groups mostly affected the potency. Kinetic studies revealed that 2, 3, and 4 inhibited maltose-hydrolyzing activity of intestinal α-glucosidase, noncompetitively. This is the first report on mammalian α-glucosidase inhibition by 1, 2 and 3 isolated from T. chebula fruits. These results suggest a use of the extract of T. chebula fruits for managing Type 2 diabetes.