α-Glucosidase Inhibitor Isolated from Blechum pyramidatum

Blechum pyramidatum (Lam.) Urb. is a species of extensive medicinal use in the American continent. In fact, antidiabetic and anticancer preparations from this plant have been patented in Mexico, even though their active constituents are not yet known. It was recently discovered that B. pyramidatum inhibits the action of the α-glucosidase enzyme, thereby corroborating the antidiabetic properties attributed to this plant. The primary purpose of this study was to identify and characterize the α-glucosidase inhibitors from this species. Bioassay-guided fractionation of a crude extract of B. pyramidatum led to the isolation of a main α-glucosidase inhibitor, Palmitic acid (IC50 237.5). This compound was identified by both spectroscopic and spectrometric analysis. Its inhibitory activity was similar to that of the antidiabetic drug acarbose (IC50 241.6 μM), which was used as a positive control in our bioassay. Kinetic analysis established that palmitic acid acted as a competitive inhibitor. Docking analysis predicted that this compound binds to the same site as acarbose does in the human intestinal α-glucosidase (PDB: 3TOP). The presence of palmitic acid in B. pyramidatum and its potent inhibitory activity against α-glucosidase enzyme provides solid evidence to support the antidiabetic use of this plant in traditional medicine.

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COMPARISON OF α –GLUCOSIDASE INHIBITORY ACTIVITY OF Moringa oleifera ETHANOLIC EXTRACT

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2021.9(spl-2-icopmes_2020).s269.s273 ◽

2021 ◽

Vol 9 (Spl-2-ICOPMES_2020) ◽

pp. S269-S273

Author(s):

Rizky Rahmwaty Alami ◽

◽

Herlina Rante ◽

Yulia Yusrini Djabir ◽

◽

...

Keyword(s):

Inhibitory Activity ◽

Moringa Oleifera ◽

Ethanolic Extract ◽

Ethanol Extract ◽

Positive Control ◽

Glucosidase Inhibitor ◽

Plant Samples

The purpose of this research was to determine the α-glucosidase enzyme inhibitory activity of Moringa oleifera plant samples collected from the three geographical areas viz., Saragi, Bacuhau, and Batumatongka of Southeast Sulawesi Indonesia. Ethanol extract of Moringa leaves was prepared by the maceration method using 95% ethanol. The estimation of α –glucosidase inhibitory activity of this extract was performed in vitro. The results of the study showed that ethanolic extract of three Moringa samples i.e. Sarangi, Bacuhau, and Batumatongka had the IC50value of 18.62, 10.18, 10.58 ppm, respectively while IC50value for the acarbose positive control was reported 11.54ppm. From the results of this study, it can be concluded that ethanolic extract of Moringa could inhibit α –glucosidase and this potential was similar to the commercial α –glucosidase inhibitor acarbose.

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α-Glucosidase Inhibitory Activity of Cycloartane-Type Triterpenes Isolated from Indonesian Stingless Bee Propolis and Their Structure–Activity Relationship

Pharmaceuticals ◽

10.3390/ph12030102 ◽

2019 ◽

Vol 12 (3) ◽

pp. 102 ◽

Cited By ~ 7

Author(s):

Niken Pujirahayu ◽

Debu Kumar Bhattacharjya ◽

Toshisada Suzuki ◽

Takeshi Katayama

Keyword(s):

Inhibitory Activity ◽

Antioxidant Activities ◽

Stingless Bee ◽

Structure Activity Relationships ◽

Glucosidase Inhibitor ◽

Structure Activity ◽

Glucosidase Inhibitors ◽

Ic50 Values ◽

New Type ◽

Treatment Of Diabetes

This study reports on the antioxidant activity and α-glucosidase inhibitory activity of five cycloartane-type triterpenes isolated from Indonesian stingless bee (Tetragonula sapiens Cockerell) propolis and their structure–activity relationships. The structure of the triterpenes was determined to include mangiferolic acid (1), Cycloartenol (2), ambonic acid (3), mangiferonic acid (4), and ambolic acid (5). The inhibitory test results of all isolated triterpenes against α-glucosidase showed a high potential for inhibitory activity with an IC50 range between 2.46 and 10.72 µM. Among the compounds tested, mangiferonic acid (4) was the strongest α-glucosidase inhibitor with IC50 2.46 µM compared to the standard (–)-epicatechin (1991.1 µM), and also had antioxidant activities with IC50 values of 37.74 ± 6.55 µM. The study on the structure–activity relationships among the compounds showed that the ketone group at C-3 and the double bonds at C-24 and C-25 are needed to increase the α-glucosidase inhibitory activity. The carboxylic group at C-26 is also more important for increasing the inhibitory activity compared with the methyl group. This study provides an approach to help consider the structural requirements of cycloartane-type triterpenes from propolis as α-glucosidase inhibitors. An understanding of these requirements is deemed necessary to find a new type of α-glucosidase inhibitor from the cycloartane-type triterpenes or to improve those inhibitors that are known to help in the treatment of diabetes.

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Phenylethyl Cinnamides as Potential α-Glucosidase Inhibitors from the Roots of Solanum Melongena

Natural Product Communications ◽

10.1177/1934578x1100600623 ◽

2011 ◽

Vol 6 (6) ◽

pp. 1934578X1100600 ◽

Cited By ~ 3

Author(s):

Xuchun Liu ◽

Jianguang Luo ◽

Lingyi Kong

Keyword(s):

Solanum Melongena ◽

Preliminary Observation ◽

Mechanism Analysis ◽

Isolation And Identification ◽

Etoh Extract ◽

Glucosidase Inhibitors ◽

Medicinal Use ◽

Competitive Inhibitors ◽

Bioassay Guided Fractionation ◽

Inhibitory Activities

Bioassay-guided fractionation against α-glucosidase resulted in isolation and identification of six phenolic compounds (1–6) from the 70% EtOH extract of the roots of Solanum melongena L. (Solanaceae). Of these, three phenylethyl cinnamides, N-trans-feruloyl tyramine (1), N-trans-p-coumaroyl tyramine (2) and N-cis-p-coumaroyl tyramine (3) possessed inhibitory activity against α-glucosidase with IC50 values of 500.6, 5.3 and 46.3 μM, respectively. Mechanism analysis revealed these phenylethyl cinnamides were non-competitive inhibitors. This is the first study of the α-glucosidase inhibitory activities of the roots of S. melongena, and this preliminary observation suggested potential medicinal use of this herb.

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Isolation of neolignan and phenolic glycosides from the branches of Viburnum macrocephalum f. keteleeri and their α-glucosidase inhibitory activity

Holzforschung ◽

10.1515/hf-2018-0081 ◽

2018 ◽

Vol 72 (12) ◽

pp. 1017-1024 ◽

Cited By ~ 3

Author(s):

Chunchao Zhao ◽

Jia Chen ◽

Jianhua Shao ◽

Jie Shen ◽

Xiaoqing Xu ◽

...

Keyword(s):

Ethyl Acetate ◽

Inhibitory Activity ◽

Ethyl Acetate Fraction ◽

Positive Control ◽

Phenolic Glycosides ◽

Isolation And Identification ◽

Bioassay Guided Fractionation ◽

First Time ◽

Deciduous Shrub

AbstractViburnum macrocephalumf.keteleeri, not well explored in the pharmaceutical field, is a tall deciduous shrub and commonly used as folk medicines for the treatment of type 2 diabetes (T2D). In this study, the dried branches ofV. macrocephalumf.keteleeriwere extracted with 95% ethanol and the extract was fractionated on the basis of polarity with ethyl acetate andn-butanol. Among the different fractions, the ethyl acetate fraction exhibited the highestα-glucosidase inhibitory activity, and its bioassay-guided fractionation led to the isolation and identification of six compounds including a new 8-O-4′-neolignan glycoside (1), categorized as a rare 7-deoxy skeleton, three previously undescribed phenolic glycosides (2–4), together with two known secondary metabolites (5,6), which were found for the first time inViburnum. Noticeably, compound1had almost the same intestinalα-glucosidase inhibitory activity as the positive control acarbose.

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Intestinal α-Glucosidase Inhibitors in Achillea millefolium

Natural Product Communications ◽

10.1177/1934578x1701200828 ◽

2017 ◽

Vol 12 (8) ◽

pp. 1934578X1701200

Author(s):

Kota Noda ◽

Eisuke Kato ◽

Jun Kawabata

Keyword(s):

Enzyme Activity ◽

Bioactive Compounds ◽

Inhibitory Activity ◽

Achillea Millefolium ◽

Major Contributor ◽

Caffeoylquinic Acids ◽

Glucosidase Inhibitor ◽

Glucosidase Inhibitors ◽

Prevention And Treatment ◽

Treatment Of Diabetes

Achillea millefolium is a plant used as a component of anti-diabetic preparation but the bioactive compounds responsible for its use are not known. Inhibition of intestinal α-glucosidase is a preferable effect for prevention and treatment of diabetes, and A. millefolium extract showed inhibitory activity against the enzyme. Activity-guided separation of the extract gave four mono- or di-caffeoylquinic acids as the isolate. Quantitation of these four caffeoylquinic acids and the activity of the isolates suggested that these are the major contributor for the α-glucosidase inhibitory activity in the extract. However also, the presence of unidentified, minor, but potent α-glucosidase inhibitor in the isolate was also suggested.

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Xanthine oxidase inhibitory activity of a new isocoumarin obtained from Marantodes pumilum var. pumila leaves

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-020-03119-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Nor-Ashila Aladdin ◽

Khairana Husain ◽

Juriyati Jalil ◽

Carla Wulandari Sabandar ◽

Jamia Azdina Jamal

Keyword(s):

Xanthine Oxidase ◽

Inhibitory Activity ◽

Positive Control ◽

Oxidase Inhibitor ◽

Bone Diseases ◽

Spectroscopic Techniques ◽

Xanthine Oxidase Inhibitor ◽

Margaric Acid ◽

Bioassay Guided Fractionation

Abstract Background In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds. Method Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques. Results The most active dichloromethane extract of M. pumilum var. pumila leaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50 value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL). Conclusion This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.

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Identification of α-Glucosidase Inhibitors from Leaf Extract of Pepper (Capsicum spp.) through Metabolomic Analysis

Metabolites ◽

10.3390/metabo11100649 ◽

2021 ◽

Vol 11 (10) ◽

pp. 649

Author(s):

Samuel Tilahun Assefa ◽

Eun-Young Yang ◽

Gelila Asamenew ◽

Heon-Woong Kim ◽

Myeong-Cheoul Cho ◽

...

Keyword(s):

Inhibitory Activity ◽

Positive Control ◽

Partial Least Square ◽

Least Square ◽

Inhibitory Potency ◽

Glucosidase Inhibitors ◽

Hydroxycinnamic Acid Derivatives ◽

Capsicum Spp ◽

Pepper Leaves

Metabolomics and in vitro α-glucosidase inhibitory (AGI) activities of pepper leaves were used to identify bioactive compounds and select genotypes for the management of type 2 diabetes mellitus (T2DM). Targeted metabolite analysis using UPLC-DAD-QToF-MS was employed and identified compounds that belong to flavone and hydroxycinnamic acid derivatives from extracts of pepper leaves. A total of 21 metabolites were detected from 155 samples and identified based on MS fragmentations, retention time, UV absorbance, and previous reports. Apigenin-O-(malonyl) hexoside, luteolin-O-(malonyl) hexoside, and chrysoeriol-O-(malonyl) hexoside were identified for the first time from pepper leaves. Pepper genotypes showed a huge variation in their inhibitory activity against α-glucosidase enzyme(AGE) ranging from 17% to 79%. Genotype GP38 with inhibitory activity of 79% was found to be more potent than the positive control acarbose (70.8%.). Orthogonal partial least square (OPLS) analyses were conducted for the prediction of the AGI activities of pepper leaves based on their metabolite composition. Compounds that contributed the most to the bioactivity prediction model (VIP >1.5), showed a strong inhibitory potency. Caffeoyl-putrescine was found to show a stronger inhibitory potency (IC50 = 145 µM) compared to acarbose (IC50 = 197 µM). The chemometric procedure combined with high-throughput AGI screening was effective in selecting polyphenols of pepper leaf for T2DM management.

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Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000652 ◽

2020 ◽

pp. 1-9

Author(s):

Pınar Ercan ◽

Sedef Nehir El

Keyword(s):

Inhibitory Activity ◽

Digestive Enzymes ◽

Positive Control ◽

Anthocyanin Content ◽

Inhibitory Effects ◽

Total Anthocyanin ◽

Total Anthocyanin Content ◽

Before And After ◽

Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

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Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

Phytothérapie ◽

10.3166/phyto-2018-0074 ◽

2018 ◽

Vol 17 (3) ◽

pp. 134-139

Author(s):

R.M. Perez-Gutierrez

Keyword(s):

Protein Tyrosine Phosphatase ◽

Inhibitory Activity ◽

Spectroscopic Data ◽

Methanol Extract ◽

Tyrosine Phosphatase ◽

Positive Control ◽

Protein Tyrosine Phosphatase 1B ◽

Protein Tyrosine ◽

Ic50 Value ◽

Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

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Evaluation of Enzyme Inhibitory Activity of Flavonoids by Polydopamine-Modified Hollow Fiber-Immobilized Xanthine Oxidase

Molecules ◽

10.3390/molecules26133931 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3931

Author(s):

Cong-Peng Zhao ◽

Guo-Ying Chen ◽

Yuan Wang ◽

Hua Chen ◽

Jia-Wen Yu ◽

...

Keyword(s):

Xanthine Oxidase ◽

Hollow Fiber ◽

Inhibitory Activity ◽

Ph Value ◽

Enzymatic Reaction ◽

Amino Acid Residues ◽

Reaction Conditions ◽

Docking Analysis ◽

Dopamine Concentration ◽

Immobilization Time

In this study, a polydopamine (PDA)-modified hollow fiber-immobilized xanthine oxidase (XOD) was prepared for screening potential XOD inhibitors from flavonoids. Several parameters for the preparation of PDA-modified hollow fiber-immobilized XOD, including the dopamine concentration, modification time, XOD concentration and immobilization time, were optimized. The results show that the optimal conditions for immobilized XOD activity were a dopamine concentration of 2.0 mg/mL in 10.0 mM Tris-HCl buffer (pH 8.5), a modification time of 3.0 h, an XOD concentration of 1000 μg/mL in 10.0 mM phosphate buffer (pH 7.5) and an immobilization time of 3.0 h. Subsequently, the enzymatic reaction conditions such as the pH value and temperature were investigated, and the enzyme kinetics and inhibition parameters were determined. The results indicate that the optimal pH value (7.5) and temperature (37 °C) of the PDA-modified hollow fiber-immobilized XOD were consistent with the free enzyme. Moreover, the PDA-modified hollow fiber-immobilized XOD could still maintain above 50% of its initial immobilized enzyme activity after seven consecutive cycles. The Michaelis–Menten constant (Km) and the half-maximal inhibitory concentration (IC50) of allopurinol on the immobilized XOD were determined as 0.25 mM and 23.2 μM, respectively. Furthermore, the PDA-modified hollow fiber-immobilized XOD was successfully applied to evaluate the inhibitory activity of eight flavonoids. Quercetin, apigenin, puerarin and epigallocatechin showed a good inhibition effect, and their percentages of inhibition were (79.86 ± 3.50)%, (80.98 ± 0.64)%, (61.15 ± 6.26)% and (54.92 ± 0.41)%, respectively. Finally, molecular docking analysis further verified that these four active compounds could bind to the amino acid residues in the XOD active site. In summary, the PDA-modified hollow fiber-immobilized XOD is an efficient method for the primary screening of XOD inhibitors from natural products.

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