Phenolic compounds isolated from Morus nigra and their α-glucosidase inhibitory activities

Abstract

A novel benzofuranone unprecedentedly with a prenyl group at C-3, nigranol A (1), a new flavonol, nigranol B (2), and three known compounds, sanggenon M (3), nigrasin C (4), and nigrasin A (5) were isolated from the twigs of Morus nigra Linn. Their structures were elucidated on the basis of the analysis of multiple spectroscopic data. All of the compounds, along with eight previously isolated ones (6–13) were investigated for their α-glucosidase inhibitory activities. The result showed that compounds 1–13 except 4 exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 2 and 7 were the best α-glucosidase inhibitory candidates with IC₅₀ values at 1.63 and 1.43?μM, respectively. Furthermore, the structure-activity relationships of the sanggenon-type flavanones were summarized.     

Chemical constituents from the flowers of Satsuma mandarin and their free radical scavenging and α-glucosidase inhibitory activities

Flowers of Citrus plants are used as mild sedatives and for the treatment of insomnia in traditional medicines. In Japan, tea made from the flowers of Satsuma mandarin is consumed as healthy drink. Hesperidin (1), hesperetin (2), rutin (3), quercetin (4), nicotiflorin (5), eriocitrin (6), narirutin (7), phenylethyl glucoside (8) and unshuoside A (9) were isolated from the MeOH extract of fresh flowers. Structure elucidation of these compounds was performed on the basis of NMR spectroscopic data. Among them, rutin (3), quercetin (4) and eriocitrin (6) showed potent free radical scavenging activity, whereas hesperetin (2) and quercetin (4) showed potent α-glucosidase inhibitory activity.     

New bisbibenzyl and phenanthrene derivatives from Dendrobium scabrilingue and their α-glucosidase inhibitory activity

Abstract

Phytochemical investigation of the whole plant of Dendrobium scabrilingue resulted in the isolation of two new compounds namely dendroscabrols A (1) and B (2), along with eight known compounds (3–10). The structures of these compounds were determined by NMR and HR-ESI-MS experiments. All of the isolates were evaluated for their α-glucosidase inhibitory effect. Dendroscabrol B (2) and RF-3192C (10) showed the most potent α-glucosidase inhibitory activity. Dendroscabrol A (1), gigantol (5), coelonin (7) and lusianthridin (9) also exhibited strong activity as compared with the positive control acarbose.     

Chemical composition and antioxidant, α-glucosidase inhibitory and antibacterial activities of three Echeveria DC. species from Mexico

Three Echeveria species from Sinaloa, Mexico (Echeveria craigiana, Echeveria kimnachii and Echeveria subrigida) were analyzed for their content of antioxidant compounds (β-carotene, ascorbic acid, α-tocopherol, total phenolics and flavonoids) and the in vitro antioxidant (DPPH, ABTS, ORAC and β-carotene bleaching [β-CBM]), α-glucosidase inhibitory and antibacterial activities. The studied Echeveria species showed high α-tocopherol content (2.9–9.0 mg/100 g f.w.) and total phenolics as Gallic Acid Equivalents (GAE) (152.2–400.5 mg GAE/100 g f.w.). Antioxidant activities of the three Echeveria methanol extracts (ME) were higher than those of other well-known plants with this property; the activities of E. craigiana (ABTS, 65.91 μmol ET/g f.w.) and E. subrigida (β-CBM, 79.3%) were remarkable. The Echeveria ME showed stronger α-glucosidase inhibition (IC₅₀ 25.21–50.57 μg/mL) than acarbose (IC₅₀ 3.59 mg/mL) as well as high antibacterial activity (Minimal Inhibitory Concentrations, MICs ⩽ 1 mg/mL), mainly against Gram positive bacteria. The results showed the three Echeveria species had components/biological activities with high potential for food/pharmacological uses and could be exploited by sustainable management schemes.     

Cumin scented leaf essential oil of Cinnamomum chemungianum: compositions and their in vitro antioxidant, α-amylase, α-glucosidase and lipase inhibitory activities

As part of our work on prospecting of Cinnamomum of the Western Ghats, chemical compositions, antioxidant, α-amylase, α-glucosidase and lipase inhibitory activities of leaf essential oil (EO) of Cinnamomum chemungianum were evaluated. Chemical characterisation of the cumin scented leaf EO from five locations in the southern Western Ghats revealed that they were highly varied. EO from Kannikatti (CC²) exhibited good α-amylase inhibitory activity with IC₅₀ value of 5.97 μg/mL, whereas the EOs from Chemungi (CC¹) and Athirumala (CC⁵) showed better α-glucosidase inhibition with IC₅₀ of 56.65 and 62.12 μg/mL, respectively. The EOs from Chemungi, Kannikatti and Athirumala were found to inhibit lipase with IC₅₀ of 919.75, 923.17 and 838.46 μg/mL, respectively. The EO of C. chemungianum may be used in food products as it has cumin scent and mild inhibitory activities.     

Antioxidant and α-glucosidase inhibitory ingredients identified from Jerusalem artichoke flowers

Jerusalem artichoke (JA, Helianthus tuberosus L.) has been researched extensively due to its wide range of uses, but there are limited studies on its flowers. In this study, we report the first detailed phytochemical study on JA flowers, which yielded 21 compounds. Compound 4 was identified as a major water-soluble yellow pigment of JA flowers. In addition, the methanol extract of JA flowers and the isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Among the tested compounds, compound 13 showed the strongest ABTS⁺ free radical scavenging activity with SC₅₀ value of 2.30 ± 0.13 μg/mL, and compound 6 showed most potent α-glucosidase inhibitory activity with inhibition rate of 60.0% ± 10.3% at a concentration of 250 μg/mL. Results showed that methanol extract of JA flowers exhibited antioxidant and α-glucosidase inhibitory activities which could be attributed to its phenolic ingredients including chlorogenic acid derivatives, flavonoids and phenols.     

New 2-arylbenzofurans from the root bark of Artocarpus gomezianus and their α-glucosidase inhibitory activity

Two new 2-arylbenzofurans, namely 13-O-methyllakoochin B (1) and artogomezianin (2), were isolated from the root bark of Artocarpus gomezianus, along with six known compounds (3–8). The structures of new compounds were determined by spectroscopic and chemical methods. All of the isolates were evaluated for their α-glucosidase inhibitory activity. Artogomezianin (2) and lakoochin A (3) exhibited strong α-glucosidase inhibitory activity with IC₅₀ values of 18.25 and 26.19 µM, respectively, as compared with the positive control acarbose.     

Physicochemical properties, in vitro antioxidant activities and inhibitory potential against α-glucosidase of polysaccharides from Ampelopsis grossedentata leaves and stems

In the present study, polysaccharides named ALPS and ASPS were isolated from Ampelopsis grossedentata leaves and stems, respectively. Physicochemical properties, in vitro antioxidant activities and the inhibitory effects on α-glucosidase of ALPS and ASPS were investigated. It was found that both ALPS and ASPS were acid protein-bound heteropolysaccharides, although with considerably different chemical composition and molecular weight distribution. Meanwhile, in comparison with ALPS, ASPS exhibited stronger antioxidant activity and inhibitory potential against α-glucosidase according to the in vitro evaluation. Moreover, our results suggested that protein and uronic acid might, at least partly, contribute positively to the biological behavior of ALPS and ASPS.     

Studies on α-glucosidase,aldose reductase and glycation inhibitory properties of sesquiterpenes and flavonoids of Zingiber zerumbet Smith

Eight known phytochemicals, four sesquiterpenes and four flavonoids of Zingiber zerumbet were screened against α-glucosidase enzyme, aldose reductase enzyme and antiglycation property under in vitro conditions. The results established kaempferol-3-O-methylether as a potent inhibitor of α-glucosidase enzyme with an IC₅₀ value of 7.88 μM. In aldose reductase enzyme inhibition assay, all the compounds except zerumbone epoxide showed good to excellent inhibition properties. Among these, the flavonoid compounds were found to be potent aldose reductase inhibitors compared with the four sesquiterpenes. In addition, compounds such as α-humulene, kaempferol, kaempferol-3-O-methylether and 3″,4″-O-diacetylafzelin displayed potent antiglycation properties. From overall results, we found that kaempferol and kaempferol-3-O-methylether are potent inhibitors of α-glucosidase enzyme, aldose reductase enzyme and glycation reaction, the three main targets of drugs for the treatment of diabetes and its complications.     

Aryl-oxadiazole Schiff bases: Synthesis, α-glucosidase in vitro inhibitory activity and their in silico studies

α-Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1–18) were synthesized and evaluated for α-glucosidase inhibitory potential. Fifteen compounds 1–8, 11–13, and 15–18 showed excellent inhibition with IC₅₀ values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC₅₀ = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC₅₀ = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α-glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data.     

Nano-Cuo–Au-catalyzed solvent-free synthesis of α-aminophosphonates and evaluation of their antioxidant and α-glucosidase enzyme inhibition activities

A new green and efficient method has been developed for the synthesis of α-aminophosphonates through one-pot three-component Kabachnik–Fields reaction. It involves the reaction of a 2-aminophenol with different substituted aromatic aldehydes and dimethyl phosphite in the presence of nanocopper oxide–gold (CuO–Au) catalyst under solvent-free conditions at 60?°C. Nano-CuO–Au catalyst was found to have many advantages like high activity, simple workup, and good (87%) to very high yields (96%). The products were characterized by IR, ¹H, ¹³C, and ³¹P NMR spectra and elemental analysis. All the synthesized compounds were screened for in vitro antioxidant and α-glucosidase inhibition activities. The compound 4b showed higher 2,2-diphenyl-1-picrylhydrazyl and H₂O₂ radical scavenging activity and compound 4e showed higher NO radical scavenging activity than the standard ascorbic acid. The compound 4j has much higher α-glucosidase enzyme inhibition activity than the standard acarbose.     

Synthesis and α-glucosidase inhibitory activity of chrysin,diosmetin, apigenin,and luteolin derivatives

Several derivatives have been synthesized from chrysin, diosmetin, apigenin, and luteolin, which were isolated from diverse natural plants. The α-glucosidase inhibitory activity of these compounds was evaluated. The glucosidase inhibitory activity of all derivatives （IC50 〈 24.396 μmol]L） was higher compared with that of the reference drug, acarbose （IC50=563.601 ±40.492μmol/L）, and 1- deoxynojirimycin （IC50 = 226.912± 12.573 μmol/L）. O3＇,O7-Hexyl diosmetin （IC50 = 2.406 ± 0.101μmol/L） was the most potent inhibitor identified. These compounds showed a higher inhibitory ability compared with their precursors except the luteolin derivatives. In general, the inhibitory activity of the synthetic derivatives was enhanced with long alkyl chains at positions 3＇, 4＇ and 7 of the flavonoid.     

Isolation of polyphenol compounds from olive waste and inhibition of their derivatives for α-glucosidase and α-amylase

Abstract

Olive waste was used as a sustainable resource because it contained a variety of valuable compounds. The polyphenols active fraction from enrichment by microporous resin and extraction with ethyl acetate were analysed by different chromatographic methods. A total of 14 polyphenolic compounds were isolated and identified by structure elucidation. Based on the above obtained compounds, tyrosol was selected as a characteristic polyphenol and participated in transesterification reaction to synthesise β-ketoester using Yb(OTf)₃. Then the Biginelli reaction with benzaldehyde, urea and ketoester (1:1.2:1.2) was performed at 90?°C for 3.0?h under the acidic condition. In addition, the β-ketoester prepared using tyrosol with benzyl had a greater inhibitory effect on α-glucosidase and α-amylase, and the inhibition of enzyme activity for 3, 4-dihydropyrimidinone derivatives prepared using abovementioned β-ketoester was improved significantly. Meanwhile, fluorine-containing dihydropyrimidinone derivatives were considerable inhibitors for both enzymes.     

A new dihydrobenzofuran lignan and potential α-glucosidase inhibitory activity of isolated compounds from Mitrephora teysmannii

A new dihydrobenzofuran lignan, (2R,3S)-2-(3′,4′-dimethoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-2,3-dihydrobenzofuran-3-methyl acetate, named as mitredrusin (1), was isolated from the leaves of Mitrephora teysmannii (Annonaceae) together with 12 known compounds including a related dihydrobenzofuran lignan: (?)-3′,4-di-O-methylcedrusin (2), four polyacetylenic acids: 13(E)-octadecene-9,11-diynoic acid (3), 13(E),17-octadecadiene-9,11-diynoic acid (4), octadeca-9,11,13-triynoic acid (5) and octadeca-17-en-9,11,13-triynoic acid (6), five lignans: (?)-eudesmin (7), (?)-epieudesmin (8), (?)-phillygenin (9), magnone A (10) and forsythialan B (11) and two megastigmans: (3S,5R,6S,7E,9R)-7-megastigmene-3,6,9-triol (12) and annoionol A (13). The chemical structures of these compounds were established on the basis of their 1-D and 2-D NMR spectroscopic data. All compounds were evaluated for their α-glucosidase inhibitory activity. Among these isolates, polyacetylenic acids 3 and 4 showed more than 20-fold much higher activity compared with that of the antidiabetic drug acarbose.     

C-methyl flavonoid from the leaves of Cleistocalyx conspersipunctatus: α-glucosidase inhibitory,molecular docking simulation and biosynthetic pathway

We extracted one new C-methyl flavonoid, farrerol 7-O-β-d-(6-O-galloyl)glucopyranoside (1), along with 11 known flavonoids, from the Cleistocalyx (C.) conspersipunctatus leaves. Elucidation of these flavonoid structures was accomplished through spectroscopic investigation and electronic circular dichroism (ECD) computation. Compared to corosolic acid (IC₅₀: 15.5 ± 0.9 μM), an established inhibitor, the compound 1 (IC₅₀: 6.9 ± 1.2 μM) was found more active in suppressing α-glucosidase. These findings imply the potential of compound 1 as a valid α-glucosidase inhibitor, which also offer evidence for future animal experiments and clinical trials. Besides, molecular docking was employed to explore the probable mechanism for α-glucosidase–compound 1 interaction. The biosynthetic pathway of these flavonoids in C. conspersipunctatus were proposed.     

New biphenantherene and nervogenic acid derivatives from Liparis regnieri Finet and their inhibitory activities against NF-κB activation

A phytochemical investigation of the whole plant of Liparis regnieri Finet led to the isolation of one new biphenantherene (1) and ten new nervogenic acid derivatives (2–11), together with nine known compounds. Their structures were elucidated mainly by extensive analyses of 1D and 2D NMR spectroscopic data and chemical reactions. Additionally, for the first time a previously unreported biphenantherene was discovered to effectively suppress TNF-α induced expression of NF-κB-Luc in Hela cells with the IC₅₀ value of 1.80 μM and the structure-activity relationshipwas also discussed.     

Screening and structural characterization of α-glucosidase inhibitors from hawthorn leaf flavonoids extract by ultrafiltration LC-DAD-MS n and SORI-CID FTICR MS

In vitro α-glucosidase inhibition assays and ultrafiltration liquid chromatography with photodiode array detection coupled to electrospray ionization tandem mass spectrometry (ultrafiltration LC-DAD-ESI-MS ⁿ ) were combined to screen α-glucosidase inhibitors from hawthorn leaf flavonoids extract (HLFE). As a result, four compounds were identified as α-glucosidase inhibitors in the HLFE, and their structures were confirmed to be quercetin-3-O-rha- (1-4)-glc-rha and C-glycosylflavones (vitexin-2″-O-glucoside, vitexin-2″-O-rhamnoside and vitexin) by high-resolution sustained off resonance irradiation collision-induced dissociation (SORI-CID) data obtained by Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS). Several other C-glycosylflavones (vitexin, isovitexin, orientin, isooriention) and their aglycones apigenin and luteolin were evaluated by in vitro assays, and were found to possess strong α-glucosidase inhibitory activities as well. Moreover, the substituent groups on the flavones had a great impact on the enzyme inhibition activity. C-3′-OH of the B-ring of flavones in particular increased the α-glucosidase inhibition activity, whereas C-glycosylations at C-6 or C-8 of the A ring weakened the inhibition activity.     

Potent α-glucosidase inhibitory activity of compounds isolated from the leaf extracts of Uvaria hamiltonii

Abstract

The phytochemical investigation of the leaf extracts of Uvaria hamiltonii (Annonaceae) led to the isolation and identification of ten compounds including a new seco-cyclohexene (1) together with nine known compounds (2–10). Their structures were elucidated by intensive analysis by spectroscopic methods and comparisons of their spectroscopic data with those of compounds reported in the literature. Compounds 2, 8, and 9 showed potent α-glucosidase inhibitory activity with the IC₅₀ values ranging from 2.6–7.1?µM.     

Facile one-pot synthesis,butyrylcholinesterase and α-glucosidase inhibitory activities,structure–activity relationship,molecular docking and DNA–drug binding analysis of Meldrum’s acid derivatives

Research on Chemical Intermediates - Meldrum’s acid derivatives were facile synthesized by one-pot condensation process and characterized by NMR (1H, 13C, DEPT-90 and DEPT-135) and EI-MS. The...     

Pycnalin, a new α-glucosidase inhibitor from Acer pycnanthum

A new compound, pycnalin (1), together with four known compounds, ginnalins A (2), B (3), C (4), and 3,6-di-O-galloyl-1,5-anhydro-D-glucitol (3,6-di-GAG) (5), were isolated from Acer pycnanthum. The structure of 1 was determined on the basis of 2D-NMR spectral data and synthesis of 1. Pycnalin (1) is the first 1,5-anhydro-D-mannitol linked to a gallic acid, while compounds 2-5 were 1,5-anhydro-D-glucitol linked to gallic acids. All compounds were tested in vitro for α-glucosidase inhibitory and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities. Pycnalin (1) exhibited moderate α-glucosidase inhibitory activity as well as free radical scavenging activity. Ginnalin A (2) and 3,6-di-GAG (5), which have two galloyl groups, exhibited potent α-glucosidase inhibition, compared to those of other compounds 1, 3, and 4 containing a galloyl group. These results suggest that α-glucosidase inhibition is influenced by the number of galloyl groups.