Strong Α-glucosidase Inhibition Research Articles

Nutritional composition, bioactive compounds, and pharmacological activities of tossa jute sprout (Corchorus olitorius L.): A potential functional food

This study investigated the food properties, phytochemical profiles, and pharmacological activities of tossa jute sprout, underscoring the exploration of its potential as a functional food. Tossa jute sprout is rich in protein, carbohydrate, fiber, total soluble solids, color content, total energy, vitamins, and minerals, with a lower fat and sugar content. Bioactive compound profiling found that it contains a significant quantity of total phenolics and flavonoids. The HPLC-DAD polyphenol profile detected ten compounds, with 3,4 dihydroxybenzoic acid being the most abundant compound, followed by (−) epicatechin, rosmarinic acid, kaempferol, catechin hydrate, caffeic acid, myricetin, catechol, trans-ferulic acid, and rutin hydrate. It has strong radical scavenging, reducing power, metal chelating power, and total antioxidant power, suggesting this sprout's ability to repair cellular oxidative damage or restore impaired cellular oxidative homeostasis. It also possesses strong α-glucosidase and pancreatic lipase inhibition activities, but mild α-amylase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibition activities support the sprout's ability to lower blood sugar, suppress postprandial hyperglycemia, downregulate fat metabolism, and maintain or restore acetylcholine. Overall findings established tossa jute sprout's high potential as a functional food in eliminating malnutrition, maintaining quality health, and eradicating or moderating ailments, including diabetes, obesity, and Alzheimer's.

New Perspectives on the Risks of Hydroxylated Polychlorinated Biphenyl (OH-PCB) Exposure: Intestinal Flora α-Glucosidase Inhibition.

Polychlorinated biphenyls (PCBs) are a group of colorless and odorless environmental pollutants with a wide range of toxic effects. Some PCBs, especially less chlorinated ones, will rapidly undergo phase I metabolism after entering the body, and hydroxylated polychlorinated biphenyls (OH-PCBs) are the main metabolites of PCBs. Intestinal flora α-glucosidase is a common carbohydrate-active enzyme which is ubiquitous in human intestinal flora. It can convert complex dietary polysaccharides into monosaccharides, assisting the body in degrading complex carbohydrates and providing energy for the survival and growth of bacterial flora. The present study aims to investigate the inhibition of the activity of intestinal flora α-glucosidase by OH-PCBs. 4-Nitrophenyl-α-D-glucopyranoside (PNPG) was used as a probe substrate for α-glucosidase, and in vitro incubation experiments were conducted to study the inhibition of 26 representative OH-PCBs on α-glucosidase. Preliminary screening of in vitro incubation was performed with 100 μM of OH-PCBs. The results showed that 26 OH-PCBs generally exhibited strong inhibition of α-glucosidase. The concentration-dependent inhibition and half inhibition concentrations (IC50s) of OH-PCBs on α-glucosidase were determined. 4'-OH-PCB 86 and 4'-OH-PCB 106 were chosen as representative OH-PCBs, and the inhibition kinetic parameters (Kis) of inhibitors for α-glucosidase were determined. The inhibition kinetic parameters (Kis) of 4'-OH-PCB 86 and 4'-OH-PCB 106 for α-glucosidase are 1.007 μM and 0.538 μM, respectively. The silico docking method was used to further analyze the interaction mechanism between OH-PCBs and α-glucosidase. All these results will help us to understand the risks of OH-PCB exposure from a new perspective.

2-Styrylchromones as inhibitors of α-amylase and α-glucosidase enzymes for the management of type 2 diabetes mellitus

α-amylase and α-glucosidase are key enzymes implicated in carbohydrate digestion and their inhibition has been suggested as a powerful approach for regulating blood glucose levels. The present work describes for the first time their inhibition by a group of twelve hydroxylated 2-styrylchromones (2-SC). Our findings revealed that 2-SC display strong systematic inhibition of α-glucosidase rather than α-amylase activity. The number and position of the hydroxy groups in the chromone moiety further modulate the inhibitory profile of the studied compounds, and the derivatives bearing one catechol unit are efficient inhibitors of both enzymes. Enzyme kinetic studies indicate that all active compounds act as competitive inhibitors of α-amylase while most of them behave as non-competitive inhibitors of α-glucosidase. The results are promising and pave the way to further deciphering the potential of this class of compounds as a suitable alternative for the management of type 2 diabetes and its complications.

Polyphenol Fingerprint, Biological Activities, and In Silico Studies of the Medicinal Plant Cistus parviflorus L. Extract.

Cistus parviflorus L. (Cistaceae) is a medicinal plant with several folkloric applications, including being used for urinary tract infections and as a food additive. In this study, the polyphenolic diversity and the antioxidant, antidiabetic, and antimicrobial activities of the C. parviflorus methanolic extract were evaluated. Spectrophotometric and HPLC-based analyses using standard polyphenolic compounds were conducted to measure the phenolics and flavonoids in the plant extract. The in vitro DPPH, ORAC, FRAP, and α-glucosidase assays were used to evaluate the plant's antioxidant and antidiabetic activities. Furthermore, disc diffusion and MIC-based microdilution tests were applied to evaluate the antimicrobial activity of the plant against broad-spectrum microorganisms. The analysis revealed the existence of high phenolic and flavonoid quantities that were measured at 302.59 ± 0.6 μg GAE and 134.3 ± 0.5 μg RE, respectively. The HPLC-based analysis revealed the existence of 18 phenolic acids and 8 flavonoids. The major phenolic acid was ellagic acid (169.03 ppm), while catechin was the major flavonoid (91.80 ppm). Remarkable antioxidant activity was measured using three different assays: DPPH, ORAC, and FRAP. Furthermore, strong inhibition of α-glucosidase compared to acarbose was recorded for the plant extract (IC50 0.924 ± 0.6). The results showed that C. parviflorus's extract had a strong anti-Escherichia coli effect with MIC value of 0.98 μg\mL and IZD value of 32.2 ± 0.58 mm compared to 25.3 ± 0.18 mm for gentamycin, the positive control. Moreover, Aspergillus niger, Aspergillus fumigatus, Staphylococcus aureus, Streptococcus pyogenes, and Salmonella typhimurium all showed significant growth inhibition in response to the extract, a result that may be related to the use of the plant in traditional medicine to treat urinary tract infections. The docking study indicated the higher binding affinity of the major identified compounds, i.e., ellagic acid, rutin, naringin, catechin, and punicalagin, to the S. aureus gyrase-DNA complex, which might suggest the possible mechanisms of the plant as antimicrobial agents.

Characterization and Evaluation of the In Vitro Antioxidant, α-Glucosidase Inhibitory Activities of Camellia longii Orel and Luu. (Theaceae) Flower Essential Oil and Extracts From Vietnam

Objective/Background: Camellia longii Orel and Luu was discovered for the first time in Cat Tien National Park of Lam Dong Province, Southern Vietnam, was determined as a new species. To the best of our knowledge, this is the first report on the phytochemical and bioactivity of this species. Methods: The chemical profile of essential oil (EO) prepared from C. longii flowers was determined by GC/MS analysis and comparison of the recorded retention indices and the corresponding literature values. The total phenolic and flavonoid contents in different flower extracts were estimated by Folin-Ciocalteu and aluminum chloride methods with a spectrophotometer, respectively. The antioxidant activities of the extracts were determined by various bioassays, including DPPH free radical scavenging, ferric reducing power, and cupric reducing antioxidant capacity. The α-glucosidase inhibitory activity of the extracts was evaluated using p-nitrophenyl α-D-glucopyranoside solution as a substrate and acarbose as the positive control. Results: Fifty-seven compounds were identified from the EO of C. longii flowers. Among these, the main components were α-eudesmol (16.1%), followed by ( E)-nerolidol (13.0%), β-eudesmol (8.9%), τ-cadinol (6.5%), and γ-eudesmol (5.8%). The total phenolic and flavonoid contents were found high in ethyl acetate, n-butanol, and ethanol extracts (206.8-378.6 mg gallic acid equivalents/g crude extract and 298.5-390.3 mg rutin equivalents/g crude extract, respectively). These extracts were shown to possess potent antioxidant activities in the examined bioassays. As for the α-glucosidase inhibitory assay, the ethyl acetate, butanol, and ethanol extracts were shown to be more potent than acarbose with IC50 values of 2.16 ± 0.04, 1.95 ± 0.05, and 1.53 ± 0.04 μg/mL, respectively. Conclusion: The findings first provide the phytochemical profiles of Camellia longii Orel and Luu and its bioactivities, indicating moderate potentials in antioxidant activity and strong α-glucosidase inhibition.

α-Glucosidase inhibition by green, white and oolong teas: in vitro activity and computational studies

Natural α-glucosidase inhibitors from plant-based foods such as catechins offer an attractive strategy for their potential anti-diabetic effects. In this study, infusions of three different tea types (green, white, and oolong) were investigated for their total phenolic (TPC) and catechins (EGCG, ECG, EGC, and EC) content, and for their α-glucosidase inhibitory activities. We observed that the level of TPC in white tea was significantly higher compared to oolong and green tea, which suggests higher content of EGCG and ECG catechins in fresh young leaves. Our findings showed that the higher content of such catechins in the infusion of white tea well correlated with a strong inhibition of α-glucosidase, and such inhibition was demonstrated to be more effective than the FDA-approved drug acarbose. Then, we computationally explored the molecular requirements for enzyme inhibition, especially for the most active catechins EGCG and ECG, as well as their disposition/stability within the active site.

Hypoglycemic effect of Coffea arabica leaf extracts and major bioactive constituents

The present study focused on investigating the antioxidant, antiglycation activity, digestive enzymes inhibition, bioaccessibility and hypoglycemic effect of C. arabica leaves extracts. The extracts deactivated the O2•-, ROO•, H2O2, HOCl reactive oxygen species. Coffee leaves showed strong inhibition of α-glucosidase (IC50 = 40.30 μg mL−1) greater than the isolated metabolites and acarbose. There was also inhibition of pancreatic lipase (IC50 = 56.43 μg mL−1) in addition to a hypoglycemic effect in zebrafish similar to acarbose and metformin. With the exception of rutin, all biocompounds were detected at all stages of in vitro digestion. Finally, these results suggest that C. arabica leaf extracts possess antidiabetic and anti-obesity properties that can be attributed to the main metabolites and the synergistic action between them. Communicated by Ramaswamy H. Sarma

A new iridoid from the roots of Valeriana jatamansi Jones with α-glucosidase activity

One new iridoid namely rupesin F (1) together with four known ones (2–5) were isolated from the roots of Valeriana jatamansi Jones. The structures were established using spectroscopic methods (1D and 2D NMR including HSQC, HMBC, COSY and NOESY) and by comparison with previously published literature data. The isolated compounds 1 and 3 exhibited strong α-glucosidase inhibition activity with IC50 values of 10.13 ± 0.11 and 9.13 ± 0.03 μg/mL, respectively. This study enriched the chemical diversity of metabolites and provides a direction for the development of antidiabetic agents.

Identification of novel α-glucosidase inhibitory peptides in rice wine and their antioxidant activities using in silico and in vitro analyses

Many peptides are contained in rice wine, which may have various bioactivities, and need to be investigated. The aim of this study was to identify novel peptides with high α-glucosidase inhibition and antioxidant activities in rice wine and to illustrate their underlying mechanisms. Peptide composition, α-glucosidase inhibition and antioxidant activities of the different elution fractions from macroporous resin adsorption chromatography were investigated. Potentially bioactive peptides were screened via in silico analyses and validated by in vitro experiments, and then, their mechanisms were further investigated by molecular docking and molecular dynamics simulations. Results showed that the peptides from 50% ethanol-eluted rice wine (50%-RP) exhibited strong α-glucosidase inhibition and antioxidant activities. Three novel peptides, SSLFR, QFTPR and FTYPR screened out by in silico analyses, were confirmed to have good α-glucosidase inhibition and antioxidant activities, and FTYPR exhibited the best bioactivities. These peptides could bind to ABTS and DPPH radicals and the active site of α-glucosidase through hydrogen bonding, Pi bonding and van der Waals forces. This study may not only provide new knowledge for the health effects of rice wine, but also supply theoretical bases for the development of health products of rice wine to improve its economic value.

Antidiabetic Activity of Manonjaya Snakefruit Skin Extract with Zebra Fish (Danio rerio) as Animal Model

This research aimed to determine the active fraction and profile of active compounds in Manonjaya sSnakefruit skin extract that can be used as antidiabetic and the antidiabetic activity using zebra fish. Manonjaya sSnakefruit skin was extracted by maceration using 70% ethanol and then fractionated using n-hexane, ethyl acetate and methanol. The ethyl acetate fraction showed the highest yield and total phenolic content as well as the strongest α-glucosidase inhibition with an inhibition percentage of 64.43%. The ethyl acetate fraction provided the most active spot as an α-glucosidase inhibitor. The profile of active compounds that act as antidiabetic compound is flavonoid from glycosylflavone and flavone groups. Antidiabetic activity using zebra fish was indicates that Manonjaya Snakefruit skin extract from ethanol extract and ethyl acetate fraction can decrease blood sugar level of zebra fish after induced with alloxan. The crude extract group had 54.51% lower sugar content than the induction group and 41.70% lower than the negative control. Meanwhile, the ethyl acetate fraction group had 65.10% lower sugar content than the induction group and 55.27% lower than the negative control.

Comparative Bio-Potential Effects of Fresh and Boiled Mountain Vegetable (Fern) Extract Mediated Silver Nanoparticles.

This current investigation was designed to synthesize Ag nanoparticles (AgNPs) using both the fresh (Fbf) and boiled (Bbf) Korean mountain vegetable fern (named Gosari) extracts and make a comparative evaluation of its multi-therapeutic potentials. The screening of phytochemicals in the fern extract was undertaken. The synthesized fern-mediated silver nanoparticles are characterized and investigated for their bio-potential like α-glucosidase inhibition, antioxidant, and cytotoxicity prospects. The obtained AgNPs were characterized by the UV-Vis Spectra, SEM, EDS, XRD, FTIR, DLS, Zeta potential analysis, etc. The synthesis of the Fbf-AgNPs was very fast and started within 1 h of the reaction whereas the synthesis of the Bbf-AgNPs synthesis was slow and it started around 18 h of incubation. The UV-Vis spectra displayed the absorption maxima of 424 nm for Fbf-AgNPs and in the case of Bbf-AgNPs, it was shown at 436 nm. The current research results demonstrated that both Fbf-AgNPs and Bbf-AgNPs displayed a strong α-glucosidase inhibition effect with more than 96% effect at 1 µg/mL concentration, but the Bbf-AgNPs displayed a slightly higher effect with IC50 value slightly lower than the Fbf-AgNPs. Both Fbf-AgNPs and Bbf-AgNPs displayed good antioxidant effects concerning the in vitro antioxidant assays. In the case of the cytotoxicity potential assay also, among both the investigated Fbf-AgNPs and Bbf-AgNPs nanoparticles, the Bbf-AgNPs showed stronger effects with lower IC50 value as compared to the Fbf-AgNPs. In conclusion, both the fern-mediated AgNPs displayed promising multi-therapeutic potential and could be beneficial in the cosmetics and pharmaceutical sectors. Though the synthesis process is rapid in Fbf-AgNPs, but it is concluded from the results of all the tested bio-potential assays, Bbf-AgNPs is slightly better than Fbf-AgNPs.

Phytochemical, Antimicrobial, Antidiabetic, Thrombolytic, anticancer Activities, and in silico studies of Ficus palmata Forssk

Ficus palmata Forssk. (Moraceae family) is medicinally valuable plant that is mostly used as folk medicine for the treatment of differentdiseases. Phytochemical composition was evaluated by preliminary phytochemical investigation, GCMS analysis, and total bioactive contents (TPC and TFC). The antioxidant, enzyme inhibition, antimicrobial, thrombolytic and anticancer activities were performed for biological evaluation. The extract exhibited the maximum total phenolic (49.24 ± 1.21 mg GAE/g) and total flavonoid contents (29.9 ± 1.13 mg QE/g) which may be correlated to higher antioxidant potential of extract. The GCMS investigation identified the presence of 27 phytocompounds of different classes related to aldehydes, esters of fatty acids, triterpenes, steroids, triterpenoid. The extract possessed the strong α-glucosidase (73.4 ± 4.65 %) and moderate α-amylase inhibition activity (47.1 ± 3.29 %). Significant results were observed in case of antiviral, antifungal, and antibacterial activities. F. palmata extract inhibited the growth of HepG2 cancer cells in a dose-dependent manner. The extract also exhibited moderate in vitro thrombolytic activity. In addition, the phytocompounds identified by GCMS were subjected to in silico molecular docking studies to analyze the binding affinity between phytocompounds and enzymes (α-glucosidase and α-amylase). Moreover, the best docked compounds were selected for ADMET studies which provide information about pharmacokinetics, physicochemical properties, drug-likeness, and toxicity of identified phytocompounds. The outcome of our research revealed that ethanolic extract of F. palmata possessed good antidiabetic, antimicrobial, thrombolytic and anticancer potential. This plant should be further explored to isolate the bioactive compounds for new drug development.

UPLC-ESI-QTOF-MS phenolic compounds identification and quantification from ethanolic extract of Myrtus communis ‘Variegatha’: In vitro antioxidant and antidiabetic potentials

Global public health is seriously threatened by diabetes and its complications. Although several synthetic drugs are currently employed for managing diabetes, however, the adverse effects associated with their use cannot be underestimated. Thus, the quest for a safe and cost-effective alternative is highly imperative. In the present study, the phenolic contents, antioxidant, antidiabetic, and cytotoxic potentials of 70% ethanolic crude extract of Myrtus communis ‘Variegatha’ were investigated using in vitro biochemical protocols. The total polyphenols content was 116.44 mg GAE/g, flavonols (6.74 mg QE/g), flavanols (2.46 mg CE/g) and the ferric reducing antioxidant power (FRAP) value was 1267.28 µmol AAE/g, 2,2-diphenyl-1-picrylhydrazyl (DPPH) (1165.37 µmol TE/g), and Trolox equivalent antioxidant capacity (TEAC) (775.52 µmol TE/g). High-resolution ultra-performance liquid chromatography coupled with electrospray ionisation/quadrupole-time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was explored to identify the phenolic compounds, most of which were flavonoids. The extract demonstrated a strong α-glucosidase inhibition potential in a concentration-dependent manner with IC50 (3.159 µg/mL), which was higher than epigallocatechin gallate (EGCG) (6.208 µg/mL), a positive control antidiabetic drug. A slight increase in glucose utilization was observed after 24 h of treatment in C3A hepatocytes at 25 μg/mL whereas an increase in glucose uptake was recorded at 25 and 50 μg/mL. The extract exhibited a cytotoxic effect (IC50 76.85 µg/mL) against C3A hepatocytes at 100 µg/mL, which correlates to the glucose utilization and uptake recorded. The findings from the study show the prospect of M. communis ‘Variegatha’ as a promising source of bioactive compounds that could be used in the development of new anti-diabetic agents, thus, further research into the plant is recommended.

Phytochemical investigation, molecular docking studies and DFT calculations on the antidiabetic and cytotoxic activities of Gmelina philippensis CHAM

Ethnopharmacological relevanceGmelina philippensis CHAM is an ornamental plant that is distributed in South Asia and warm regions of the Mediterranean area. The plant is traditionally applied in folk medicine for the treatment of diabetes. Aim of the studyTo evaluate the cytotoxic and the antidiabetic activities of the ethanolic extract of G. philippensis aerial parts. To isolate the metabolite(s) responsible for these activities and to elucidate the mechanism of action by molecular docking study. Materials and methodsCompounds (1–11) were isolated using various chromatographic techniques and their structures were determined by NMR spectroscopic and mass spectrometric analysis. The cytotoxic effect was tested using viability test and MTT assay. Antidiabetic activity was evaluated by measuring the inhibitory activity of the ethanolic extracts and compounds against α-glucosidase and α-amylase activities. Modeling and docking simulations were performed using Molecular Operating Environment software and the crystal structure of protein kinases CDK2, (1PYE) and AKT1 (4GV1), in addition to α-glucosidase (3TOP) and α-amylase (2QV4). ResultsCompounds 2, 3 and 8 were isolated for the first time from the plant and identified as: gmelinol (2), apigenin (3) and tyrosol (8). While β-sitosterol-3-O- β-D-glucopyranoside (4) vicenin-II (7), rhoifolin (9), isorhoifolin (11) were isolated for the first time from the genus, along with and the new iridoid 6-O-α-L-(2″-O-benzoyl-4″-O-trans-p-methoxycinnamoyl)rhamnopyranosyl-1α- β-D-glucopyranoside catalpolgenin (6). In addition, to the previously reported compounds: mixture of β -sitosterol and stigmasterol (1), and 6- O- α-L-(2″,3″,4″-tri-O -benzoyl)rhamnopyranosylcatalpol (5) and 6-O-α-L-(2″-O-trans-p-methoxycinnamoyl)rhamnopyranosylcatalpol (10). The cytotoxic activity against hepatocellular carcinoma (HepG-2) cell lines for compounds 2, 5, 7, 9 and 11 was conducted using cisplatin as a standard. Gmelinol (2) exhibited strong cytotoxic activity against HepG-2 cell lines with IC 50 value of 3.6 ± 0.1 μg/ml which is more potent than the standard cisplatin IC 50 = 8.7 ± 0.9 μg/ml. Molecular modeling of 2 against diverse targets of protein kinases suggested that CDK-2 and AKT-1 could be the dual probable kinase targets for its cytotoxic action. Compound 2 showed α-amylase inhibition activity with IC 50 value of 60.9 (μg/ml) while, compounds 5 showed strong α-glucosidase inhibition activity with IC 50 values of 41.7 (μg/ml) compared to acarbose with IC 50 value of 34.7, 30.6 (μg/ml). Molecular docking of compounds 2 and 5 on α-glucosidase (3TOP) and α-amylase (2QV4) enzymes revealed high binding affinity and active site interactions comparable to native ligand acarbose. ConclusionThe ethanolic extract of G. philippensis CHAM aerial parts is effective against HepG-2 cell lines, α-amylase and α-glucocidase activities. Biologically guided isolation indicated that compounds 2 and 5 are responsible for these activities. These results were supported by DMF calculations that detected the molecular areas responsible for protein interactions shown via docking studies.

In vitro evaluation of antidiabetic, antidementia, and antioxidant activity of Artemisia capillaris fermented by Leuconostoc spp

Artemisia capillaris (AC) extract was fermented with probiotic Leuconostoc mesenteroides MKJW, MKSR, Leu. mesenteroides KCTC 3719 (LM), and Leu. citreum KCTC3526 (LC), and their physiological effects were evaluated. Both MKJW and MKSR had the highest number of viable cells and metabolites, such as dextran, lactic acid, acetic acid, and mannitol, at 24 h fermentation. The fermentation metabolites were significantly correlated to strong α-glucosidase inhibition of MKJW and MKSR. MKJW fermented AC showed the highest α-glucosidase inhibition (76.05%), followed by MKSR (68.34%), LC (50.39%), LM (39.43%), AC extract supplemented with medium (CON1; 10.95%), and AC extract (CON2; −2.99%) at 24 h fermentation. The MKSR fermentation maintained intrinsic acetyl- and butyrylcholinesterase inhibitory activity of AC. Significant increase in antibacterial activity against tested ten foodborne pathogenic bacteria was found in ACs fermented by MKJW and MKSR compared to other fermented and non-fermented ACs. Our findings suggested that probiotic Leu. mesenteroides MKJW and MKSR could be used as probiotic starters in AC extract to improve multi-biological activities.

The effect of extraction solution pH level on the physicochemical properties and α-glucosidase inhibitory potential of Fucus vesiculosus polysaccharide

In this study, five Fucus vesiculosus polysaccharides (FVPs; FVP-2, FVP-4, FVP-7, FVP-10, and FVP-13) were extracted by different pH, and their physicochemical characteristics and α-glucosidase inhibitory activity were investigated. Results showed that extraction pH significantly affected the chemical composition, molecular weight, zeta potential, structure characterization, and rheological property of FVPs. The viscosity consistency index of Fucus vesiculosus polysaccharides at high concentration (40 mg/mL) were ranked in decreasing order as FVP-10 > FVP-4 > FVP-7 > FVP-2 > FVP-13, which was strictly in accordance with the order of Mw. Among the five polysaccharides, FVP-13 showed the strongest α-glucosidase inhibitory activity, which might be related to its the lowest Mw and relatively higher xylose content. Fluorescence quenching analysis indicated that the interaction of FVPs and α-glucosidase was predominated by a dynamic mechanism. Thermodynamic analysis showed that the main driving forces for the interaction was hydrophobic interaction. Circular dichroism spectrum analysis found that FVPs could induce the secondary structure of α-glucosidase changes like the decrease of β-sheet content and the increase of β-turn and random coil content to inhibit α-glucosidase activity. These results suggested that extraction with high pH was an efficient method to obtain FVPs with strong α-glucosidase inhibition activity.

Phytochemical Profiling, In Vitro Biological Activities, and In-Silico Studies of Ficus vasta Forssk.: An Unexplored Plant.

Ficus vasta Forssk. (Moraceae family) is an important medicinal plant that has not been previously investigated for its phytochemical and biological potential. Phytochemical screening, total bioactive content, and GCMS analysis were used to determine its phytoconstituents profile. Antioxidant, antibacterial, antifungal, anti-viral, cytotoxicity, thrombolytic, and enzyme inhibition activities were examined for biological evaluation. The plant extract exhibited the maximum total phenolic (89.47 ± 3.21 mg GAE/g) and total flavonoid contents (129.2 ± 4.14 mg QE/g), which may be related to the higher antioxidant potential of the extract. The extract showed strong α-amylase (IC50 5 ± 0.21 µg/mL) and α-glucosidase inhibition activity (IC50 5 ± 0.32 µg/mL). Significant results were observed in the case of antibacterial, antifungal, and anti-viral activities. The F. vasta extract inhibited the growth of HepG2 cells in a dose-dependent manner. The GCMS analysis of the extract provided the preliminary identification of 28 phytocompounds. In addition, the compounds identified by GCMS were subjected to in silico molecular docking analysis in order to identify any interactions between the compounds and enzymes (α-amylase and α-glucosidase). After that, the best-docked compounds were subjected to ADMET studies which provide information on pharmacokinetics, drug-likeness, physicochemical properties, and toxicity. The present study highlighted that the ethanol extract of F. vasta has antidiabetic, antimicrobial, anti-viral, and anti-cancer potentials that can be further explored for novel drug development.

Synthesis of Sulfur-Containing Analogues of Hedychenone, a Labdane Diterpenoid from Hedychium spicatum.

The labdane diterpene hedychenone, isolated from Hedychium spicatum, is an example of a furan-containing natural product. Herein, a new and efficient method for the synthesis of 19 new thio analogues of hedychenone is reported. The present methodology exhibits a broad substrate scope with good to excellent yields without metal or base under mild reaction conditions. The natural compound 1 and four semisynthetic derivatives (3a, 3b, 3i, and 3j) exhibited strong α-glucosidase inhibition activity with IC50 values of 15.93 ± 0.29, 9.70 ± 0.33, 11.82 ± 0.06, 12.23 ± 0.33, and 12.15 ± 0.14 μg/mL, respectively. In addition, compound 3e (6.0 ± 0.04 mm; zone of inhibition) displayed antibacterial activity against Staphylococcus aureus. This study increases the chemical diversity of bioactive hedychenone derivatives and provides a direction for the development of antidiabetic agents.

GC–MS profiling, phytochemical and biological investigation of aerial parts of Leucophyllum frutescens (Berl.) I.M. Johnst. (Cenizo)

Leucophyllum frutescens (Berl.) I.M. Johnst has been used as a crude drug for treating various respiratory ailments, dysentery, cataract and liver disorders in the folk medicine systems by the inhabitants of America and Mexico. The Phytochemical and biological investigation was established by spectrophotometrically and chemical profiling was performed by GC–MS analysis. The chemical profiling by GC–MS analysis revealed that HELE majorly contains 9-octadecenoic acid (Z)-, methyl ester, pentadecanoic acid, 14-methyl-, methyl ester, 2,6-bis(3,4-methylenedioxyphenyl)-3,7-dioxabicyclooctane, (+)-sesamin, 9,12-octadecadienoic acid, methyl ester, 9,12,15-octadecatrienoic acid, ethyl ester, (Z,Z,Z)-, n-hexadecanoic acid, hexadecanoic acid, ethyl ester, phytol, methyl stearate, cyclohexanone, 1H,3H-Furo[3,4-c]furan, 1,4-bis(3,4-dimethoxy phenyl)tetrahydro-, [1R-(1.alpha.,3a.alpha.,4.alpha.,6a.alpha.)]-, and squalene. Strong inhibition of α-glucosidase and urease enzymes was observed by HELE (IC50 0.3321 mg.mL−1) and CHLE (IC50 4.711 mg.mL−1) extracts, respectively. Phytochemical quantification revealed high TPC by BULE (189.369±1.393 mg GA.Eq.gm−1 DE ± S.D) and high TFC by CHLE (232.458±1.589 mg Qu.Eq.gm−1 DE ± S.D). CHLE presented with highest antioxidant content equivalent to Trolox, by five different spectrophotometric methods such as TAA, DPPH, TEAC, FRAP, and CUPRAC. The study concludes that L. frutescens possesses significant antioxidant, antidiabetic and cytotoxic activities indicating that L. frutescens as a potential candidate for discovery of novel phytochemical products and industrial applications.

Peptide conjugates of 18β-glycyrrhetinic acid as potent inhibitors of α-glucosidase and AGEs-induced oxidation

18β-Glycyrrhetinic acid (18β-GA) is known for several biological activities, and has been the focus of extensive research for the development of therapeutic agents. In the current study, 18β-GA-peptide conjugates 2-11 were evaluated for their in vitro α-glucosidase inhibitory and antiglycation activities. Structure-activity relationship (SAR) established and molecular interactions of active bioconjugates with the enzyme's binding sites were predicted through molecular modeling approach. In tripeptide moiety of conjugates 2−11, peptide residue at position 1 was found to have a significant role on α-glucosidase inhibition. The most active 18β-GA-peptide conjugates 5 (18β-GA-Cys1-Tyr2-Gly3), and 8 (18β-GA-Pro1-Tyr2-Gly3) exhibited several-fold potent α-glucosidase inhibition (IC50 values 20–28 μM), as compared to standard drug acarbose (IC50 = 875.8 ± 2.10 µM). Kinetic studies of potent compounds, 4–8 revealed that conjugate 5 exhibits competitive-type of inhibition, while conjugates 6–8 showed a non-competitive type of inhibition. The simulation studies also supported the kinetic results that conjugate 5 (18β-GA-Cys1-Tyr2-Gly3) inhibits the α-glucosidase enzyme by blocking its substrate binding site. AGEs-induced NO• inhibitors play an important role in controlling the inflammation associated with diabetes mellitus. The peptide conjugates 2–11 were also evaluated in vitro for AGEs-induced NO• inhibition using RAW 264.7 macrophage cell line. Our data revealed that conjugates 7–10 were the more potent AGEs-induced NO• inhibitors, comparable to standards rutin, and PDTC. The peptide conjugate 5 (a competitive inhibitor of α-glucosidase) also exhibited a strong inhibitory activity against AGEs-induced NO• production. Furthermore, peptide conjugates 2–11 were found non-cytotoxic to mouse fibroblast NIH-3T3, and murine macrophages RAW 264.7 cell lines. In conclusion, our data demonstrates that besides possessing strong α-glucosidase inhibition, the newly synthesized peptide conjugates also alleviated the AGEs-induced NO• production in RAW macrophages. Dual inhibition of α-glucosidase enzyme, and AGEs-induced NO• production by 18β-GA-peptide conjugates qualify them for further research in anti-diabetic drug discovery.