Antidiabetic Activity Research Articles

Evaluation of antioxidant, catalytic and antidiabetic activity of Phaseolus vulgaris (French green bean) mediated nickel oxide and copper doped nickel oxide bimetallic nanoparticles

In this study, nickel oxide nanoparticles (NPs) and copper doped NiO bimetallic nanoparticles (Cu@NiO BMNPs) were synthesized using Phaseolus vulgaris extracts as reducing and stabilizing agents by sol gel methods. The chemical and physical properties of synthesized NiO NPs and Cu@NiO BMNPs were confirmed by various techniques, like UV Visible spectrophotometer (UV–Vis), Fourier transform infrared spectroscopy (FTIR), Scanning Electron Microscope (SEM), Energy Dispersive X-ray (EDX), Transmission Electron Microscope (TEM) and X-ray diffraction (XRD) analysis. The optical properties of both NPs observed by UV–Vis analysis with well-defined peak and band gap value 3.2 eV & 2.62 eV. FTIR analysis confirmed the presence of functional group of NPs with fruits extract. The morphology of NPs was confirmed by SEM and TEM analysis as polygonal, rod and spherical shape. The elements present in NPs were confirmed by EDX analysis. The crystalline size calculated based on the XRD analysis was 49.78 nm and 53.66 nm for NiO and Cu@ NiO NPs respectively which were found to be slightly smaller than particle size determined from SEM and TEM micrograph. Antioxidant activity of NPs was examined using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging radicals, Catalytic activities were screened by the degradation of Methylene blue (MB) and by the inhibition of alpha-amylase enzyme, antidiabetic activity of NPs were evaluated using acarbose as standard drug. The Cu@NiO BMNPs showed 77.60 % antioxidant, 76.98 % photocatalytic and 88.86 % antidiabetic activity, which were found to be more as compared to NiO NPs. The NiO and Cu@NiO BMNPs were synthesized for the first-time using P. vulgaris extracts. This study clearly showed that P. vulgaris extracts mediated mono- and bimetallic NPs were more stable and biocompatible than their respective bulk particles.

Assessment of the in vitro anti-diabetic activity with molecular dynamic simulations of limonoids isolated from Adalia lemon peels

Limonoids are important constituents of citrus that have a significant impact on promoting human health. Therefore, the primary focus of this research was to assess the overall limonoid content and isolate limonoids from Adalia lemon (Citrus limon L.) peels for their potential use as antioxidants and anti-diabetic agents. The levels of limonoid aglycones in the C. limon peel extract were quantified through a colorimetric assay, revealing a concentration of 16.53 ± 0.93 mg/L limonin equivalent. Furthermore, the total concentration of limonoid glucosides was determined to be 54.38 ± 1.02 mg/L. The study successfully identified five isolated limonoids, namely limonin, deacetylnomilin, nomilin, obacunone 17-O-β-D-glucopyranoside, and limonin 17-O-β-D-glucopyranoside, along with their respective yields. The efficacy of the limonoids-rich extract and the five isolated compounds was evaluated at three different concentrations (50, 100, and 200 µg/mL). It was found that both obacunone 17-O-β-D-glucopyranoside and limonin 17-O-β-D-glucopyranoside possessed the highest antioxidant, free radical scavenging, and anti-diabetic activities, followed by deacetylnomilin, and then the limonoids-rich extract. The molecular dynamic simulations were conducted to predict the behavior of the isolated compounds upon binding to the protein's active site, as well as their interaction and stability. The results revealed that limonin 17-O-β-D-glucopyranoside bound to the protein complex system exhibited a relatively more stable conformation than the Apo system. The analysis of Solvent Accessible Surface Area (SASA), in conjunction with the data obtained from Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and Radius of Gyration (ROG) computations, provided further evidence that the limonin 17-O-β-D-glucopyranoside complex system remained stable within the catalytic domain binding site of the human pancreatic alpha-amylase (HPA)-receptor. The research findings suggest that the limonoids found in Adalia lemon peels have the potential to be used as effective natural substances in creating innovative therapeutic treatments for conditions related to oxidative stress and disorders in carbohydrate metabolism.

In-Vitro evaluation of antidiabetic, antioxidant, and anti-inflammatory activities in Mucuna pruriens seed extract

BackgroundMucuna pruriens var. utilis (Wall. ex Wight) belonging to the family Fabaceae. Renowned for its diverse array of phytochemicals, this plant has been historically employed in the treatment of various ailments. The objectives of this study are to evaluate the anti-diabetic, anti-inflammatory, and antioxidant properties of the optimized M. pruriens var. utilis seed extract.MethodsThe in-vitro anti-inflammatory activity of M. pruriens var. utilis ethanolic extracts was scrutinized using the Human Red Blood Cell (HRBC) method. To evaluate antioxidant activity, ABTS and DPPH assays were employed. Furthermore, the antidiabetic activity was assessed through α-amylase and α-glucosidase inhibition assays.ResultsIn the ethanolic extract of M. pruriens var. utilis numerous phytoconstituents were found by doing a phytochemical analysis (alkaloids, flavonoids, phenols, saponins, steroids, glycosides, tannins). The total phenolic and flavonoid content were determined to be 112.07 ± 1.21 mg of gallic acid equivalents GAE/g and 101.41 ± 1.08 mg of quercetin equivalents QE/g respectively. In this investigation ethanolic extract of M. pruriens var. utilis exhibited a high anti-inflammatory, antioxidant and antidiabetic activities in a dose-dependent manner. The M. pruriens var. utilis extract shows that anti-inflammatory activity 32.26 ± 3.23%, potent antioxidant effect by ABTS radical scavenging assay IC50 67.46 ± 1.45 µg/mL and DPPH radical scavenging assay IC50 63.34 ± 2.27 µg/mL and in addition, showed promising antidiabetic potential by inhibiting α-amylase IC50 33.42 ± 1.35 µg/mL and α-glucosidase IC50 28.34 ± 1.41 µg/mL.ConclusionThese findings provide additional support for the traditional medicinal use of M. pruriens var. utilis in treating inflammation, oxidative stress, and diabetes mellitus.

Lokāt (Eriobotrya japonica; family: Rosaceae): Nutritional and Medicinal Properties, in the Light of Unani Medicine and Scientific Studies

Eriobotrya japonica Lind. (Family: Rosaceae) named as loquat, is a subtropical fruit, which is well known medicinal plant cultivated in Japan and China. Various parts, like leaves, peels and fruits have been shown to possess various useful health benefits. In Unani medicine, it is vastly utilized in many illnesses, like fevers, nausea, de-arranged sanguinous humour (diseases due to morbidity of blood), indigestion, liver diseases, vomiting, dysentery, wounds, inflammations etc. Loquat plant contains many active constituents, such as glycosides, flavonoids, polyphenolic compounds, tannin etc. and nutritional and mineral compounds like, carotenoids, vitamins, starch, amino acids, sugar and others. According to various pharmacological studies it is found that the plant has many biological effects like antitussive, anti-melanogenic, anti-diabetic, anti-inflammatory, antimicrobial, kidney protective, hepatoprotective and hypolipidemic activity. This review aims to shed light on the therapeutic applications of loquat based on both traditional Unani literature and scientific studies conducted on different parts of the plant.

Nutritional, phytochemistry, antioxidant, and antidiabetic potentials of Hippocratea velutina (Afzel.) leaves: In vitro, ex vivo and in silico studies

BackgroundHippocratea velutina is a novel folk plant that is used for lowering blood glucose and is hence a potential source of new antidiabetic medication. Therefore, this study was designed to investigate the antidiabetic and antidiabetic potential of the methanol extract of Hippocratea velutina leaves. MethodsThe nutritional, elemental, and phytochemical properties of H. velutina leaves were investigated. 1,1-diphenyl-2-picrylhydrazine (DPPH) scavenging ability, Fe2+chelation and nitric oxide scavenging abilities, FeSO4-induced pancreatic injury parameters such as catalase, GSH, ENTPase, Na/K ATPase activities, α-glucosidase and α-amylase inhibitory activities were used to assess the antioxidant and antidiabetic properties of H. velutina leaf. Furthermore, HPLC-identified constituents of H. velutina leaf methanol extract were docked against human α-glucosidase (3TOP) and human α-amylase (1B2Y). ResultsThe results revealed that H. velutina contains protein, crude fat, flavonoids, anthraquinones, magnesium, sodium, and iron. Compared with quercetin, H. velutina significantly scavenged NO• radicals and chelated Fe2+. H. velutina exhibited a greater inhibitory effect on FeSO4-induced pancreatic injury. Furthermore, H. velutina showed a dose-dependent increase in the activity of ENTPDase and the Na/K ATPase enzyme, and it also had a significantly greater inhibitory effect on α-amylase and α-glucosidase enzymes than metformin. Computational study revealed that lutein showed the highest binding free energy to 3TOP, while apigenin offered the highest binding free energy to 1B2Y. ConclusionHippocratea velutina leaf possesses significant antioxidant and antidiabetic activities.

Synthesis, in vitro and in silico study of novel 1,3-diphenylurea derived Schiff bases as competitive α-glucosidase inhibitors.

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 μM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase (K i = 3.96 ± 0.0048 μM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients.

In vitro insulinotropic actions of extracts of Gnetum africanum welw and effects on glucose homeostasis in mice with diet-induced obesity-diabetes

IntroductionGnetum africanum leaf is consumed as a vegetable in many parts of Africa. Many ethnobotanical surveys indicate its usage in the management of inflammation-related diseases (such as diabetes). However, mechanisms underlying its antidiabetic actions are poorly understood. MethodsThis study conducted phytochemical analysis and investigated mechanisms underlying anti-diabetic actions of aqueous extracts of G. africanum in cellular and high fat-fed mice models of diabetes. Reversed phase high performance liquid chromatography (HPLC) analysis, qualitative phytochemical screening and the estimation of the total flavonoid and total phenolic content were conducted. Mechanisms underlying insulinotropic actions of the extracts as well as its effects on cytotoxicity, cell viability, intracellular calcium and membrane potential were assessed. In vivo actions were evaluated in mice with diet-induced obesity-diabetes. ResultsG. africanum has total phenolic content of 1.24±0.23GE/g and total flavonoid content of 1.54±0.06QE/g. HPLC analysis revealed the presence of the presence of atropine, vicenin 3, vicenin 2, alpha-chaconine, isoswertisin and solanidine. The extract stimulated non-toxic, concentration-dependent insulin-release from BRIN-BD11 cells (1.3-fold to 3.3-fold, P < 0.05 to P < 0.001). As glucose concentration increased from 1.1 mM to 5.6 mM and 5.6 mM to 16.7 mM, these effects increased by 2.0-fold (P < 0.001) and 1.2-fold (P < 0.05) respectively. Insulinotropic effects increased in cells depolarised with KCl (30 mM, 1.3-fold, P < 0.05). These effects reduced in the presence of diazoxide (300 µM, 67 %, P < 0.001), verapamil (50 nM, 50 %, P < 0.001), and absence of extracellular calcium (55 %, P < 0.001). Membrane potential (48 %, P < 0.05) and intracellular calcium (34 %, P < 0.05) increased in cells incubated with the extract. The extract improved glucose tolerance (22.2 %, P < 0.01 at 150 mg kg-1 bw; 35.1 %, P < 0.001 at 300 mg kg-1 bw) and plasma insulin levels (1.4-fold, P < 0.05 at 150 mg kg-1 bw; 2.9-fold, P < 0.001 at 300 mg kg-1 bw) in high fat fed mice in a dose-dependent manner. ConclusionThese results suggest a role for the KATP-dependent pathway in G. africanum insulinotropic actions and encourage further development of the therapeutic potential of the extract.

In‐Vitro Antimicrobial, Antidiabetic and Anticancer Activities of Calyptocarpus Vialis Extract and its Integration with Computational Studies

AbstractCalyptocarpus vialis (C. vialis), a plant of Asteraceae family exhibits nutritional value, antioxidant properties and has potential for various other biomedical applications. The present study is focused to assess the antimicrobial, antidiabetic, and anticancer potential of C. vialis extract and its integration with computational studies. The antimicrobial activity is performed against the Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis) pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) bacteria and Saccharomyces cerevisiae (S. cerevisiae), Candida albicans (C. albicans) fungi using disc diffusion method. Maximum Zone of Inhibition (ZOI) of 37±3.2 and 35±2.9 mm is obtained for S. aureus and B. subtilis respectively, whereas ZOI of 39±2.8 mm is obtained against C. albicans at dose of 500 μg/mL. The extract shows strong α‐amylase inhibition activity with IC50 ~46.8±0.81 μg/mL inferring about its antidiabetic potential. Anticancer activity of C. vialis extract is checked against HCT‐116 and DU‐145 cell lines using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium‐bromide (MTT) assay, which shows excellent anticancer activity with IC50 value of 38.09±0.65 μg/ml and 36.34±1.05 μg/ml respectively. The obtained results are further verified using computational studies considering interaction among phytochemicals and selected targets. Extract is found potent for biological activities and promising candidate for development of new drugs.

In-Depth Mass Spectrometry Study of Vanadium(IV) Complexes with Model Peptides.

Investigating the speciation of vanadium complexes in the presence of potential biomolecular targets under physiological conditions remains challenging, and further experimental techniques are needed to better understand the mechanism of action of potential metallodrugs. The interaction of two model peptides (angiotensin I and angiotensin II) with three well-known oxidovanadium(IV) compounds with antidiabetic and/or anticancer activity, [VIVO(pic)2(H2O)], [VIVO(ma)2], and [VIVO(dhp)2] (where pic, ma, and dhp are picolinate, maltolate, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate anions, respectively), was investigated by ESI-MS/MS (electrospray ionization tandem mass spectrometry) and complemented by EPR (electron paramagnetic resonance) spectroscopy measurements and theoretical calculations at the DFT (density functional theory) level. The results demonstrated that vanadium-peptide bonds are preserved after HCD (higher energy collisional dissociation) fragmentation, allowing for the identification of binding sites through a detailed analysis of the fragmentation spectra. Angiotensin I (AT1) and angiotensin II (AT2) exhibited different coordination behaviors. AT1, with two His residues (His6, His9), prefers to form [AT1 + VOL] adducts with both histidine residues coordinated to the metal ion, while AT2, which has only His6, can bind the metal in a monodentate fashion, forming also [AT2 + VOL2] adducts. Insights from this study pave the way to ESI-MS/MS investigations of more complex systems, including target proteins and further development of vanadium-based drugs.

Phytochemical Diversity and Biological Effects of Juniperus thurifera L., Essential Oil : A Comparative Study using In Vitro and In Silico Methods.

This study aims to elucidate the phytochemical diversity and biological activities of J. thurifera essential oil (JTEO) through a comparative analysis of samples from two distinct regions: Tensift-Al Haouz and Azilal, using both in vitro and in silico methods. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed 21 components in the Tensift-Al Haouz JTEO (99.99% of the oil) and 23 components in the Azilal JTEO (99.58% of the oil), with oxygenated monoterpenes being the predominant compounds in both. The biological activities were assessed in vitro. Antioxidant properties, evaluated using DPPH, FRAP, and ABTS assays, showed significant activity in both oils. Antibacterial activity was tested against two strains of Gram-positive and two strains of Gram-negative bacteria, with both oils demonstrating notable bacterial growth inhibition. Enzymatic assays assessed the antidiabetic (α-amylase and α-glucosidase), dermo-protective (tyrosinase and elastase), and neuroprotective (AChE and BChE) activities. Both oils displayed substantial inhibitory effects across all tested activities, with variations attributed to their distinct chemical compositions. In silico analyses of six target enzymes confirmed significant binding affinities of the major compounds. Notably, 2,2'-Thiobis(6-tert-butyl-p-cresol) exhibited strong binding affinities with AChE, BChE, α-amylase, α-glucosidase, tyrosinase, and elastase, with binding energies ranging from -10.0 to -6.2 kcal/mol.

A Comparison Between Microcapsules of Antioxidant Fraction of Stevia: an Evaluation of Physicochemical Parameters, Stability, Bioaccessibility, and Antidiabetic Capacity

Introduction: The antioxidant fraction of Stevia rebaudiana has important antidiabetic potential, is poorly soluble, and has low stability, which makes its applicability difficult. Materials and Methods: In this study, Stevia's fraction was obtained, characterized by Ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLCMS/ MS), and microencapsulated with maltodextrin (MDF), gum arabic (GAF), whey protein + maltodextrin (MDWF), and whey protein + gum arabic (GAWF). Then, the following parameters were evaluated: stability and antioxidant capacity over 30 days, physicochemical characteristics, preservation of bioactive compounds by digestion, and in vitro antidiabetic activity. Results and Discussion: The microcapsule with gum arabic showed better microencapsulation efficiency, while its version with maltodextrin provided increased solubility. Microencapsulation reduced the humidity and water activity in the microcapsules, except for the microcapsules containing gum arabic. The combination of maltodextrin and whey protein showed greater luminosity and a whiter powder. The microcapsules with maltodextrin and its mixture with gum arabic kept the phenolic compounds stable for 30 days. The microencapsulation with whey protein increased the antioxidant activity after 15 days of the process and during in vitro digestion. All samples showed 96% inhibition of the α-glucosidase enzyme, and only the microcapsule with maltodextrin inhibited α-amylase (58%). Conclusion: This study showed paramount results so that Antioxidant Stevia Fraction (ASF) can effectively be an adjuvant product to prevent and treat diabetes.

Design, Synthesis, molecular dynamic analysis, and In-Vivo anti-diabetic evaluation of novel hydrazine carboximidamide derivatives

Diabetes is one of the most rapidly growing health problems globally, and researchers working hard to develop novel efficient therapies against it. In this regard, hydrazine carboximidamide has a great deal of attention owing to its diverse biological activities. Herein, a new series of N, N-disubstituted hydrazine carboximidamide derivatives was designed, synthesized, and assessed for their antidiabetic activity. Docking studies were performed to initially evaluate the binding of the designed compounds to the target enzyme. It was found that all of the pivotal ligand-enzyme interactions, including the interactions with Glu205/Glu206 aminoacids were observed in docking studies. The molecular dynamic analysis showed that the antidiabetic activity of the newly developed compounds may be implemented through the inhibition of dipeptidyl peptidase 4 (DPP-4), an important target that involves enhancing insulin release and suppressing glucagon discharge from the pancreas. The target molecules were synthesized practically and all the newly-developed chemical structures were confirmed via spectrophotometric methods, including IR, LC-MS, 1H NMR, and 13C NMR techniques. Finally, the in-vivo studies were carried out to confirm the results obtained from the docking and molecular dynamics studies. Compounds 6b and 6d demonstrated improved glucose tolerance through oral glucose tolerance tests in NMRI mice (at a dose of 10 mg/kg). Furthermore, prolonged administration of compounds 6b and 6d to diabetic Wistar rats for 14 days led to a noteworthy reduction in blood levels of glucose, akin to the effects observed with sitagliptin, a standard diabetes medication.

Discovering the anti-diabetic potential of pomegranate peel metabolites by examining molecular interplay with the thioredoxin-interacting protein.

Medicinal plants like Punica granatum (pomegranate) have traditional uses against diabetes, inflammation and other diseases. The study was initiated to get an insight into the interaction tendency of P. granatum derived compounds with diabetes associated human thioredoxin-interacting protein (TXNIP). High glucose in diabetes induces production of TXNIP resulting in β-cells apoptosis. Its inhibition might reduce the diabetes incidence. To elucidate the therapeutic potential of P. granatum peel against diabetes through GC-MS based identification of extracted compounds followed by application of computational algorithms. P. granatum peel extracts were screened for antioxidant, anti-inflammatory, anti-diabetic, antimicrobial and wound healing properties. Phytochemical and GC-MS based analysis were performed to identify the bioactive compounds. Molecular docking analysis was performed by Auto Dock Vina to predict the binding tendency of P. granatum derived compounds with TXNIP. The peel exhibited antioxidant, anti-inflammatory and anti-diabetic activities, which were attributed to phytochemicals like phenols, tannins and steroids. GC-MS analysis identified 3,5-octadien-2-one, 1H-pyrrole -2,5-dione, Beta-D-lyxofuranoside, 5-O-(beta-D-lyxofuranosyl)-decyl, diethyl phthalate, 9-octadecenoic acid (Z)-, methyl ester, hexadecanoic acid, methyl ester, n-hexadecanoic acid, tetradecane, 2,6,10-trimethyl, bis (2-ethylhexyl) phthalate, decane, 3,8-dimethyl, 9-octadecenoic acid (Z)-, methyl ester and bis (2-ethylhexyl) phthalate in P. granatum peel extracts. Docking analysis revealed high binding affinities of bis (2-ethylhexyl) phthalate and 9-octadecenoic acid with TXNIP i.e., -4.5 and -5.0 kcal/mol, respectively, reflecting these compounds as potent antidiabetic agents. This study validates the traditional uses of P. granatum peel and demonstrates how computational approaches can uncover pharmacologically active phytochemicals. The results suggest P. granatum peel is a promising source of novel therapeutics against diabetes, inflammation, and oxidation. Further studies on the optimization of identified ligands are warranted.

Wogonin Alleviates Streptozotocin-stimulated Diabetic Nephropathy Through Its Antidiabetic, Antidyslipidemic, and Antioxidative Effects in Rats

Background Diabetes mellitus (DM) is a prolonged endocrine syndrome recognized by defective metabolism of biomolecules on account of flaws in insulin resistance. Diabetic nephropathy (DN) is a central microvascular complication of DM with inadequate treatment alternatives. Wogonin (WOG) is a pharmacologically active flavonoid isolated from the roots of Scutellaria baicalensis Georgi, which exerts strong renoprotection. However, the defensive mechanism of WOG against DN is not completely illuminated. Purpose This study investigates the role of WOG in streptozotocin (STZ)-induced DN in high-sucrose-high-fat fed rats. Methods DM was induced in experimental rats by a solo dosage of STZ (40 mg/kg) administered intraperitoneally. All rats were allocated into five sets, namely, normal, diabetic control (DC), metformin (150 mg/kg), and WOG (25 and 50 mg/kg) treated orally for 2 months. Results The antidiabetic and renoprotective effects of WOG were assessed by analyzing lipid profiles, glucose, inflammatory mediators, oxidative stress markers, renal functional parameters, gain in body weight, and histopathology of the kidney. In the current study, WOG could improve DM-induced metabolic alterations, dyslipidemia, kidney dysfunction, and inflammatory and oxidative prominence over its antidiabetic, antioxidative, antihyperlipidemic, and anti-inflammatory actions. Conclusion Thus, WOG is employed as a nephroprotective agent in DC rats.

Synthesis of furo[2,3-c]carbazoles as potent α-glucosidase and α-amylase inhibitors

The carbazole-3-carbaldehyde 2, produced by N-ethyl carbazole via Vilsmeier-Haack reaction, was subjected to Dakin type oxidation with H2O2 and H2SO4 in methanol to produce the carbazole-3-ol 3. The reaction of 3 with a range of commercially available α-haloketones 4a–f in the presence of Al2O3 as catalyst in xylene led to their regio-selective cyclization to afford the furo[2,3-c]carbazoles 5a–f. Identification of the furo[2,3-c]carbazoles 5a–f were performed through 1H NMR,13C NMR, FT-IR and high resolution mass spectrometry. Single crystal X-ray diffraction analysis was employed to further confirm the structures of the some of the targeted compounds. In vitro antidiabetic activities of the newly synthesized furocarbazoles 5a–e were investigated utilizing α-glucosidase and α-amylase enzymes. The biological evaluation revealed the obvious efficiencies of the targeted molecules toward the α-glucosidase enzyme inhibition with the potent IC50 values compared to the standard acarbose. In the case of α-glucosidase inhibition, the furo[2,3-c]carbazoles chloro substituted 5c and nitro substituted 5f were found to be more potent than acarbose with the values of 215.0 and 162.70 μM, respectively. On the other hand, the compound 5f was found to be only promising candidate for α-amylase enzyme but not as effective as the standard acarbose.

In silico analysis reveals α-amylase inhibitory potential of Taraxerol (Coccinia indica) and Epoxywithanolide-1 (Withania coagulans): a possible way to control postprandial hyperglycemia-induced endothelial dysfunction and cardiovascular events.

Postprandial hyperglycemia (PPG) exacerbates endothelial dysfunction and impairs vascular function in diabetes as well in healthy people. Though synthetic drugs are available to regulate PPG, the severe gastrointestinal side effects of those medications have prompted the search for alternative treatments. Recently, some phytochemicals captured the attention because of their inhibitory effects on α-amylase to control diabetes. The aim of this study was to investigate and identify potential alpha-amylase inhibitors in C. indica and W. coagulans. This study also aims to understand one of the possible mechanisms of action of plants for their anti-diabetic activity. A total of 36 phytochemical ligands were subjected for protein-ligand docking analysis. Among the phytochemicals, Taraxerol and Epoxywithanolide-I demonstrated significant binding free energy of -10.2kcal/mol and -11.9kcal/mol respectively, which was higher than the reference acarbose with -8.6kcal/mol. These molecules were subjected for molecular dynamics simulation (MDS) analysis with alpha-amylase protein for a duration of 150ns. Among the three complexes, Taraxerol and Epoxywithanolide-I complexes demonstrates strong potential as inhibitors of the target protein. MDS results were analyzed via root mean square deviation (RMSD), fluctuation of residues, potential energy, radii of gyration and solvent access surface area analysis. Taraxerol demonstrated a significantly low potential energy of -1,924,605.25kJ/mol, and Epoxywithanolide-I demonstrated -1,964,113.3kJ/mol of potential energy. RMSD plot shows that Epoxywithanolide-I has much higher stability than the other MDS complexes. Drugability and toxicity studies show that the test ligands are demonstrating strong potential as drug like molecules. The results of the study conclude that, Taraxerol of C. indica and Epoxywithanolide-I of W. coagulans are strong inhibitors of alpha-amylase enzyme and that, this is one of the possible mechanisms of action of the plants for their reported anti-diabetic activities. Further in-vitro analysis is in demand to prove the observed results.

Characterization of phenolic compounds in watermeal (Wolffia globosa) through LC-ESI-QTOF-MS/MS: assessment of bioactive compounds, in vitro antioxidant and anti-diabetic activities following different drying methods

Characterization of phenolic compounds in watermeal (Wolffia globosa) through LC-ESI-QTOF-MS/MS: assessment of bioactive compounds, in vitro antioxidant and anti-diabetic activities following different drying methods

Identification of pancreatin inhibitors from Thai medicinal Piper plants for antidiabetic and anti-obesity activities using high-performance thin-layer chromatography-bioautographic assay

Exploring the potential of natural products against diabetes and obesity is in demand nowadays. Pancreatic α-amylase and pancreatic lipase are the drug targets to minimize the absorption of glucose from starch and fatty acids from lipids, respectively. In this study, five Piper species, namely P. sarmentosum (Ps), P. wallichii (Pw), P. retrofractum (Pr), P. nigrum (Pn), and P. betle (Pb), which are commonly used as food ingredients and traditional medicines, were evaluated for their inhibitory activities against pancreatin using the microtiter plate method. Additionally, pancreatin inhibitors were identified through a cost-effective high-performance thin-layer chromatography (HPTLC)-bioautography developed using red starch and p-nitrophenyl palmitate, corresponding to anti-amylase and -lipase activities, respectively. Of the 15 samples tested, leaf samples from Pb, which had the highest total phenolic and total flavonoid contents, exhibited remarkable inhibitory activity against pancreatin, with a relative amylase inhibitory capacity (RAIC) ranging between 4.260 × 10−5 and 4.861 × 10−5 and a reciprocal half-maximal inhibitory concentration (1/IC50, PTL) of 0.390–0.510 (mg/mL)−1. Additionally, Ps samples demonstrated the second-ranked anti-pancreatin activity. Principal component analysis indicated that total phenolic content contributed to the anti-pancreatin activities of Pb samples. The anti-pancreatin bands were isolated and identified as caffeic acid, myricetin, genistein, piperine, and eugenol. Myricetin, in the roots of Ps samples, showed notable anti-pancreatin activity, which was consistent with results from the in silico prediction toward pancreatic α-amylase and pancreatic lipase. Caffeic acid and eugenol were present in Pb samples. In conclusion, the developed cost-effective pancreatin HPTLC-bioautography efficiently identified amylase and lipase inhibitors from Piper herbs, which supported the use of these plants for antidiabetes and anti-obesity.

Mechanism of inhibition of alpha-amylase by caffeic acid using in-vitro and in-silico techniques

Type-two diabetes, characterised by insulin resistance or inadequate insulin production, is prevalent among adults. The α-amylase enzyme contributes to carbohydrate digestion, elevating postprandial glucose levels. Natural compounds like caffeic acid offer a solution. This study investigates α-amylase inhibition via in-vitro and in-silico methods, emphasising the connection between phenolic compounds and antidiabetic efficacy for in-silico analysis. Enzyme kinetics, IC50, and molecular docking examine caffeic acid’s inhibitory action on α-amylase, comparing it with gallic acid and acarbose. Caffeic acid outperforms acarbose with an IC50 of 4.505 mg/mL versus 16.81 mg/mL, showcasing strong antidiabetic activity. Caffeic acid’s superior 1,1-diphenyl-2-picrylhydrazyl (DPPH) inhibition (90.67%) compared to gallic acid (55.76%) indicates potent antioxidative and antidiabetic properties. Molecular docking reveals hydrogen bonding between caffeic acid and α-amylase. These insights lay the groundwork for phenolic-based diabetic therapies, offering less expensive treatment for diabetes patients.

Discovery of tetrahydro γ-carboline based novel glucose uptake agent for the treatment of diabetes and Alzheimer’s diseases

The emergence of diabetes mellitus (DM), one of the prevalent metabolic disorders, has increased at alarming rates around the globe in the past few decades. The early discovery of insulin paved the way for the broadened non-invasive anti-hyperglycemic drug therapies to manage and treat diabetes. Recently, insulin resistance in brain tissues has been considered a new hallmark of disease progression, leading to neurodegeneration. Tetrahydro γ-carbolines are privileged scaffolds with various activities against obesity, cancer, and central nervous system (CNS) diseases. The failure of Latrepirdine in clinical phase trials as anti-AD, prompted us to explore further the γ-Carboline derivatives with anti-diabetic activity. To address this, we have leveraged our expertise in drug design to develop tetrahydro γ-carboline derivatives and studied their effect on glucose uptake. All the compounds exhibited low cytotoxicity towards the mammalian cell line 3T3-L1. Next, we screened the 10 derivatives to identify the novel anti-diabetic activities using a fluorescent glucose analog 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)-2-deoxy-D-glucose) based on a glucose-uptake assay in differentiated 3T3-L1 adipocytes. Compound 11a has significantly increased glucose uptake at 100 µM compared to rH-Insulin. The dose optimization (1 nM-100 nM) of lead compounds for 2-NBDG-glucose uptake clearly indicated that 11a is superior compared to Insulin. The 11a is the close analog of Latrepirdine, an anti-histamine drug, reported for Alzheimer disease (AD). Further, to understand its anti-AD potential we carried out in silico docking studies with its probable targets, Acetylcholinesterase (AChE), 5-hydroxytryptamine (5HT6) receptor, Butyrylcholinesterase (BChE), and N-methyl-D-aspartate (NMDA) receptor. The docking studies revealed that 11a had stronger binding to these targets than Latrepirdine, correlating with the glucose uptake assay. Thus, 11a is a potential lead disease-modifying agent and could be considered for the management and treatment of type 2 DM and AD.