Screening Of Α-glucosidase Inhibitors Research Articles

Fast screening of α-glucosidase inhibitors from Ginkgo biloba leaf by using α-glucosidase immobilized on magnetic metal-organic framework.

In this study, a ligand fishing method for the screening of α-glucosidase inhibitors from Ginkgo biloba leaf was established for the first time using α-glucosidase immobilized on the magnetic metal-organic framework. The immobilized α-glucosidase exhibited enhanced resistance to temperature and pH, as well as good thermal stability and reusability. Two ligands, namely quercitrin and quercetin, were screened from Ginkgo biloba leaf and identified by ultra-high performance liquid chromatography-tandem mass spectrometry. The half-maximal inhibitory concentration values for quercitrin and quercetin were determined to be 105.69±0.39 and 83.49±0.79µM, respectively. Molecular docking further confirmed the strong inhibitory effect of these two ligands. The proposed approach in this study demonstrates exceptional efficiency in the screening of α-glucosidase inhibitors from complex natural medicinal plants, thus exhibiting significant potential for the discovery of antidiabetic compounds.

Screening of potential α-glucosidase inhibitors from astragalus membranaceus by affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS method

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors.

Cerium-Based Metal–Organic Framework Nanocrystals for Colorimetric Screening of α-Glucosidase Inhibitors

Cerium-Based Metal–Organic Framework Nanocrystals for Colorimetric Screening of α-Glucosidase Inhibitors

New α-Glucosidase Inhibitors from the Whole Plant of Hypericum beanii Based on Ligand Fishing and Molecular Networking Analysis.

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 μM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.

Screening of α-Glucosidase Inhibitors in Cichorium glandulosum Boiss. et Huet Extracts and Study of Interaction Mechanisms.

Cichorium glandulosum Boiss. et Huet (CGB) extract has an α-glucosidase inhibitory effect (IC50 = 59.34 ± 0.07 μg/mL, positive control drug acarbose IC50 = 126.1 ± 0.02 μg/mL), but the precise enzyme inhibitors implicated in this process are not known. The screening of α-glucosidase inhibitors in CGB extracts was conducted by bioaffinity ultrafiltration, and six potential inhibitors (quercetin, lactucin, 3-O-methylquercetin, hyperoside, lactucopicrin, and isochlorogenic acid B) were screened as the precise inhibitors. The binding rate calculations and evaluation of enzyme inhibitory effects showed that lactucin and lactucopicrin exhibited the greatest inhibitory activities. Next, the inhibiting effects of the active components of CGB, lactucin and lactucopicrin, on α-glucosidase and their mechanisms were investigated through α-glucosidase activity assay, enzyme kinetics, multispectral analysis, and molecular docking simulation. The findings demonstrated that lactucin (IC50 = 52.76 ± 0.21 μM) and lactucopicrin (IC50 = 17.71 ± 0.64 μM) exhibited more inhibitory effects on α-glucosidase in comparison to acarbose (positive drug, IC50 = 195.2 ± 0.30 μM). Enzyme kinetic research revealed that lactucin inhibits α-glucosidase through a noncompetitive inhibition mechanism, while lactucopicrin inhibits it through a competitive inhibition mechanism. The fluorescence results suggested that lactucin and lactucopicrin effectively reduce the fluorescence of α-glucosidase by creating lactucin-α-glucosidase and lactucopicrin-α-glucosidase complexes through static quenching. Furthermore, the circular dichroism (CD) and Fourier transform infrared spectroscopy (FT-IR) analyses revealed that the interaction between lactucin or lactucopicrin and α-glucosidase resulted in a modification of the α-glucosidase's conformation. The findings from molecular docking and molecular dynamics simulations offer further confirmation that lactucopicrin has a robust binding affinity for certain residues located within the active cavity of α-glucosidase. Furthermore, it has a greater affinity for α-glucosidase compared to lactucin. The results validate the suppressive impact of lactucin and lactucopicrin on α-glucosidase and elucidate their underlying processes. Additionally, they serve as a foundation for the structural alteration of sesquiterpene derived from CGB, with the intention of using it for the management of diabetic mellitus.

GAA/(Au–Au/IrO2)@Cu(PABA) reactor with cascade catalytic activity for α-glucosidase inhibitor screening

BackgroundIn vitro screening strategies based on the inhibition of α-glucosidase (GAA) activity have been widely used for the discovery of potential antidiabetic drugs, but they still face some challenges, such as poor enzyme stability, non-reusability and narrow range of applicability. To overcome these limitations, an in vitro screening method based on GAA@GOx@Cu-MOF reactor was developed in our previous study. However, the method was still not satisfactory enough in terms of construction cost, pH stability, organic solvent resistance and reusability. Thence, there is still a great need for the development of in vitro screening methods with lower cost and wider applicability. ResultsA colorimetric sensing strategy based on GAA/(Au–Au/IrO2)@Cu(PABA) cascade catalytic reactor, which constructed through simultaneous encapsulating Au–Au/IrO2 nanozyme with glucose oxidase-mimicking and peroxidase-mimicking activities and GAA in Cu(PABA) carrier with peroxidase-mimicking activity, was innovatively developed for in vitro screening of GAA inhibitors in this work. It was found that the reactor not only exhibited excellent thermal stability, pH stability, organic solvent resistance, room temperature storage stability, and reusability, but also possessed cascade catalytic performance, with approximately 12.36-fold increased catalytic activity compared to the free system (GAA + Au–Au/IrO2). Moreover, the in vitro GAA inhibitors screening method based on this reactor demonstrated considerable anti-interference performance and detection sensitivity, with a detection limit of 4.79 nM for acarbose. Meanwhile, the method owned good reliability and accuracy, and has been successfully applied to the in vitro screening of oleanolic acid derivatives as potential GAA inhibitors. SignificanceThis method not only more effectively solved the shortcomings of poor stability, narrow scope of application, and non-reusability of natural enzymes in the classical method compared with our previous work, but also broaden the application scope of Au–Au/IrO2 nanozyme with glucose oxidase and peroxidase mimicking activities, and Cu(PABA) carrier with peroxidase mimicking activity, which was expected to be a new generation candidate method for GAA inhibitor screening.

Diphenolic boldine, an aporphine alkaloid: inhibitory effect evaluation on α-glucosidase by molecular dynamics integrating enzyme kinetics

Screening α-glucosidase inhibitors with novel structures is an important field in the development of anti-diabetic drugs due to their application in postprandial hyperglycemia control. Boldine is one of the potent natural antioxidants with a wide range of pharmacological activities. Virtual screening and biochemical inhibition kinetics combined with molecular dynamics simulations were conducted to verify the inactivation function of boldine on α-glucosidase. A series of inhibition kinetics and spectrometry detections were conducted to analyze the α-glucosidase inhibition. Computational simulations of molecular dynamics/docking analyses were conducted to detect boldine docking sites’ details and evaluate the key binding residues. Boldine displayed a typical reversible and mixed-type inhibition manner. Measurements of circular dichroism and fluorescence spectrum showed boldine changed the secondary structure and loosened the tertiary conformation of target α-glucosidase. The computational molecular dynamics showed that boldine could block the active pocket site through close interaction with binding key residues, and two phenolic hydroxyl groups of boldine play a core function in α-glucosidase inhibition via ligand binding. This investigation reveals the boldine function on interaction with the α-glucosidase active site, which provides a new inhibitor candidate. Communicated by Ramaswamy H. Sarma

A magnetic beads-based ligand fishing method Coupled with UHPLC-QTOF MS for screening and identification of α-glucosidase inhibitors from Houttuynia cordata Thunb

In this study, a method for the screening and identification of α-glucosidase inhibitors from natural products was developed. The α-glucosidase was immobilized on carboxyl terminated magnetic beads to form a ligand fishing system to screen the potential inhibitors. A total of 9 compounds were fishing out from the crude Houttuynia cordata Thunb. extract. Meanwhile, ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS) was used for the identification of the chemical structures, including 3 chlorogenic acid isomers, 2 flavone C-glycosides and 4 flavone O-glycosides. The combination of enzyme immobilization magnetic beads and UHPLC-QTOF MS could be used for the screening of bioactive multi-components from herbs with appropriate targets. Taking the advantage of the specificity of enzyme binding and the convenience of magnetic separation, the method has great potential for rapid screening of α-glucosidase inhibitors from complicated natural product extracts.

Screening of α-glucosidase inhibitors in tea by amino-functionalized mesoporous SBA-15 immobilized α-glucosidase microreactor

NH2-SBA-15 was prepared as an enzyme loading microreactor by modifying SBA-15 with 3-aminopropyltriethoxysilane as the functionalizing reagent. After modification, α-glucosidase (α-Glu) can be easily and fast immobilized on the surface and inner wall of the two-dimensional pores of NH2-SBA-15 by electrostatic adsorption in phosphate buffered saline (PBS, pH 7.4). The quantity of immobilized α-Glu by NH2-SBA-15 under the optimum conditions was 39.93 μg mg−1 which was much higher than unmodified SBA-15 (15.92 μg mg−1), and the enzyme activity still retained 76.1% after 7 cycles. In addition, due to the restricted conformational change of the immobilized enzyme in the 2D pore structure, which had some protective effect on the enzyme, the immobilized enzyme had good acid and alkali resistance, and high temperature resistance. The results showed that the relative activity of the immobilized enzyme fluctuated less in the same pH range, and still retained more than 90% of the activity after standing at 40 °C and 60 °C for 24 h. Finally, the NH2-SBA-15-α-Glu microreactors were co-incubated with the tea extract, and the α-Glu inhibitory active components were screened by HPLC. Several chemical components were successfully screened out, verifying the feasibility of the microreactor.

Screening for α-glucosidase inhibitors from Selaginella uncinata based on the ligand fishing combined with ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry.

Biflavonoids are naturally occurring compounds consisting of two flavonoid moieties that have received substantial attention from researchers. Although many kinds of biflavonoids are typically distributed in Selaginella uncinata with hypoglycemic effect, their anti-α-glucosidase activities are not yet clear. In this study, a ligand fishing strategy for fast screening of α-glucosidase inhibitors from S. uncinata was proposed. α-Glucosidase was first immobilized on Fe3 O4 magnetic nanoparticles (MNPs) and then the α-glucosidase-functionalized MNPs were incubated with crude extracts of S. uncinata to fish out the ligands. Furthermore, considering the similarity and easy confusion of the structures of biflavonoids, the fragmentation patterns of different types of biflavonoids were studied. Based on this, 11 biflavonoids ligands with α-glucosidase inhibitory activities were accurately and quickly identified from S. uncinata with ultra-high-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry. Furthermore, these ligands were confirmed to be potential inhibitors through the in vitro inhibitory assay and molecular docking.

Identification of yeast α-glucosidase inhibitors from Pueraria lobata by ligand fishing based on magnetic mesoporous silicon combined with knock-out/knock-in technology.

In this study, a ligand fishing technique based on magnetic mesoporous silicon was established and used to screen α-glucosidase inhibitors from Pueraria lobata. To clarify quantity-activity relationships in a holistic view, the knock-out/knock-in technology was used to analyse the interactions of several active constituents in P. lobata. Magnetic mesoporous silicon with a large specific surface area and better biocompatibility was synthesised. Subsequently, α-glucosidase was immobilised on -NH2-modified magnetic mesoporous silicon, and the compounds in the crude extract of P. lobata were screened across enzyme binding. The structures of the ligands were elucidated using UPLC-Q-TOF-MS/MS, and their activities were verified by knock-out/knock-in experiments and molecular docking. Daidzein and puerarin showed α-glucosidase inhibitory activities with an IC50 of 0.088 ± 0.003 mg mL-1 and 0.414 ± 0.005 mg mL-1, respectively. Among them, puerarin, which accounted for more than 40% of the total content, showed synergistic effects with other components and was the main contributor to the α-glucosidase inhibitory activity of P. lobata.

Cascade reaction biosensor based on gold nanocluster decorated iron-cobalt oxide nanosheets as a superior peroxidase mimic for dual-mode detection of α-glucosidase and its inhibitor

Herein, we have synthesized a novel kind of gold nanoclusters decorated iron-cobalt oxide nanosheets (His-AuNCs@FeCo-ONSs) assembled by electrostatic interaction, which possessed both outstanding peroxidase-like activity and fluorescence property. Taking advantage of our bifunctional hybrid nanozyme and enzyme cascade reactions, a sensitive dual-mode (colorimetric/fluorescent) detection method for α-glucosidase was constructed. The detection limits for α-glucosidase were 2.2 U/L and 3.3 U/L in fluorometric and colorimetric mode, respectively. This method not only provides high sensitivity, but also can correct itself to improve the accuracy of analysis due to the dual-response signals. Furthermore, it was employed for α-glucosidase determination in real samples and screening of α-glucosidase inhibitors.

Screening of α-glucosidase inhibitors in large-leaf yellow tea by offline bioassay coupled with liquid chromatography tandem mass spectrometry

Larger-leaf yellow tea (LYT) is a characteristic type of Chinese tea produced in Huoshan County, Anhui Province, which is made by mature leaves with stems. According to recent report, LYT showed competitive effects in anti-hyperglycemia in comparison to other teas such as green or black tea. However, the bioactive compounds of LYT are still undiscovered so far. For this purpose, 5 fractions of LYT were prepared by sequential extraction. The in vitro bioassay results indicated that the ethyl acetate fraction of LYT had the strongest inhibitory effects on α-glucosidase and α-amylase. Fluorescence-quenching analysis and protein-binding test revealed that the compounds of ethyl acetate fraction could inhibit α-glucosidase and α-amylase activities through binding to enzymes or other mechanisms. All chromatographic peaks of high-performance liquid chromatography (HPLC) of ethyl acetate fraction were separated and collected. The purified compounds were identified by liquid chromatography-mass spectrometry (LC-MS), and subsequently screened by calculating their inhibition ratio on α-glucosidase at the real concentration in LYT infusion. The results showed that (–)-epigallocatechin gallate, (–)-gallocatechin gallate, caffeine, N-ethyl-2-pyrrolidone-substituted flavan-3-ols were effective inhibitors for α-glucosidase.

Copper-carbon dot aerogel: a high-performance mimetic peroxidase and its application for versatile colorimetric bioassays.

Three-dimensional hierarchically porous copper-carbon dot aerogels (Cu-CDA) were fabricated on a large scale using copper as metal nodes and carbon dots derived from adenine and sodium citrate as building blocks. Benefiting from the electron transfer process and generation of hydroxyl radicals, Cu-CDA exhibited a high peroxidase-like activity. Combining the observation with multienzyme cascade reactions, versatile colorimetric bioassays of hydrogen peroxide as well as diabetes-associated glucose and α-glucosidase were explored and then extended to screen α-glucosidase inhibitors that are used as antidiabetic and antiviral agents.

Critical Assessment of In Vitro Screening of α-Glucosidase Inhibitors from Plants with Acarbose as a Reference Standard.

Postprandial hyperglycemia is treated with the oral antidiabetic drug acarbose, an intestinal α-glucosidase inhibitor. Side effects of acarbose motivated a growing number of screening studies to identify novel α-glucosidase inhibitors derived from plant extracts and other natural sources. As "gold standard", acarbose is frequently included as the reference standard to assess the potency of these candidate α-glucosidase inhibitors, with many outperforming acarbose by several orders of magnitude. The results are subsequently used to identify suitable compounds/products with strong potential for in vivo efficacy. However, most α-glucosidase inhibitor screening studies use enzyme preparations obtained from nonmammalian sources (typically Saccharomyces cerevisiae), despite strong evidence that inhibition data obtained using nonmammalian α-glucosidase may hold limited value in terms of identifying α-glucosidase inhibitors with actual in vivo hypoglycemic potential. The aim was to critically discuss the screening of novel α-glucosidase inhibitors from plant sources, emphasizing inconsistencies and pitfalls, specifically where acarbose was included as the reference standard. An assessment of the available literature emphasized the cruciality of stating the biological source of α-glucosidase in such screening studies to allow for unambiguous and rational interpretation of the data. The review also highlights the lack of a universally adopted screening assay for novel α-glucosidase inhibitors and the commercial availability of a standardized preparation of mammalian α-glucosidase.

Screening and functional evaluation of the glucose-lowering active compounds of total saponins of Baibiandou (Lablab Semen Album)

ObjectiveTo screen for α-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity in vivo. MethodsAcarbose was used as the positive control, and the median inhibitory concentration (IC50) was used as the evaluation index of α-glucosidase inhibitory activity to establish an in vitro α-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of α-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived α-glucosidase and human-derived α-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice. ResultsThis study successfully identified 15 compounds with potential α-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong α-glucosidase inhibitory activity. The α-glucosidase inhibitory concentration IC50 was (565.2 ± 1.026) μg/mL, and the IC50 of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived α-glucosidase and human-derived α-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (P < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent. ConclusionThis study provides a basis for screening α-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).

Identification of α-glucosidase inhibitors from the bran of Chenopodium quinoa Willd. by surface plasmon resonance coupled with ultra-performance liquid chromatography and quadrupole-time-of-flight-mass spectrometry

Extracts from the bran of Chenopodium quinoa Willd. (QBE) were reported to be active in inhibiting α-glycosidase, a promising target for treatment of diabetes mellitus. However, the constituents responsible for the α-glucosidase-inhibiting activity of QBE have not been fully characterized. The present study aimed to set up a method for rapid identification of glycosidase inhibiting compounds from the quinoa bran. With surface plasmon resonance (SPR) coupled with liquid chromatography-mass spectrometry (LC-MS), we identified eight flavonoids and ten triterpenoid saponins that may bind to the α-glycosidase. Analysis of the interaction kinetics by molecular docking supported their α-glucosidase-inhibiting activity and revealed the potential mechanisms for the inhibitory effects. In summary, this study established a SPR and LC-MS-based method for rapid in vitro screening of α-glucosidase inhibitors and suggested the quinoa bran a potential natural source of α-glucosidase inhibitors.

Dopamine‐polyethyleneimine co‐deposition of a capillary for α‐glucosidase immobilization and its application in enzyme inhibitor screening

An online method based on CE was established to screen α-glucosidase inhibitors from traditional Tibetan medicine extracts. First, the inner wall at the inlet of capillary column was simply and effectively functionalized by dopamine-polyethyleneimine co-deposition method, which combines the adhesion property of dopamine and easy cationization of polyethyleneimine. Then α-glucosidase was rapidly immobilized on the inner wall of the capillary column by electrostatic adsorption. The inter- and intraday repeatability of the peak area of the enzymatic reaction product (p-nitrophenol) in a capillary was evaluated, and RSD% (n = 3) was 0.94% and 1.09%, respectively. Good batch-to-batch reproducibility of the peak area between different capillaries (RSD = 2.1%, n = 5) shows that the preparation method has good reproducibility. The Michaelis-Menten constant of the immobilized α-glucosidase was measured to be 1.18mM, and the capillary column enzyme reactor retained 85.9% of initial activity after 30 cycles. Finally, it was applied to the screening of enzyme inhibitors in 20 traditional Tibetan medicine extracts. Sixteen medicines with inhibitory activity were screened out, and Rheum australe had the strongest inhibitory effect with an inhibitory rate of 83.3± 0.4%. These results showed that this method is effective to find potential enzyme inhibitors.

Personal Glucose Meter for α-Glucosidase Inhibitor Screening Based on the Hydrolysis of Maltose.

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.

Screening α-glucosidase inhibitors from four edible brown seaweed extracts by ultra-filtration and molecular docking

This research aimed to screen potential α-glucosidase inhibitors (AGIs) from Sargassum pallidum, Ecklonia kurome, Hizikia fusiforme and Undaria pinnatifida Suringar. Acetone was the best solvent to extract polyphenolic compounds in brown seaweeds with high total phenolic content. After concentrating with AB-8 macroporous resin, the enriched EtOH extract of Hizikia fusiforme extracts (HFEE) had the highest total phenolic content with 60.2 mg GAE/g E. The enriched acetone extract of Sargassum pallidum (SPEA) indicated the best α-glucosidase inhibitory effect with IC50 value of 270.7 μg/mL. A total of 21 potential α-glucosidase inhibitors were separated from four brown seaweed extracts by ultrafiltration, and included 2 phenolic acids, 5 terpenes, 4 flavonoids, 5 fatty acids, 3 simple phenolic compound, 1 ester and 1 other compound. The main constituents were palmitic acid (0.40–1.21 mg/g), poricoic acid A (0.58–1.62 mg/g), n-hexacosyl caffeate-hexose (0.92–2.37 mg/g), quercetin-3-O-glucuronide (1.02 mg/g in SPEA) and 6- gingerol (1.06–1.87 mg/g). Molecular docking has showed that poricoic acid A and quercetin-3-O-glucuronide could bind the active sites of α-glucosidase and form 4 and 6 hydrogen bonds in ligand-enzyme complex, and then caused the inhibition activity on α-glucosidase. The results showed the significant potential of Sargassum pallidum to be explored as AGIs.