Glycation Inhibitory Activity Research Articles

Exploring anti-diabetic potential of compounds from roots of Dendrobium polyanthum Wall. ex Lindl. through inhibition of carbohydrate-digesting enzymes and glycation inhibitory activity

Eight compounds, including one anthraquinone, two bibenzyls, one phenanthrene, three dihydrophenanthrenes, and one flavonoid, were isolated from the roots of Dendrobium polyanthum Wall. ex Lindl. Among these, six compounds were investigated for inhibitory activities against alpha-glucosidase, alpha-amylase, and advanced glycation end products (AGEs) production. Additionally, molecular docking was conducted to analyze the interactions of the test compounds with alpha-glucosidase. Moscatin, the only isolated phenanthrene, displayed the strongest anti–alpha-glucosidase activity with an IC50 of 32.45 ± 1.04 μM, approximately 10-fold smaller than that of acarbose. Furthermore, moscatilin most strongly inhibited alpha-amylase and AGEs production with IC50 values of 256.94 ± 9.87 and 67.89 ± 9.42 μM, respectively. Molecular docking analysis revealed the effective binding of all substances to alpha-glucosidase with smaller lowest binding energy values than acarbose. Moscatin was selected for kinetics studies, and it was identified as a non-competitive inhibitor with approximately 9-fold greater inhibitory capability than acarbose. This study represents the first report on the phytochemical constituents and antidiabetic potential of compounds derived from the roots of D. polyanthum Wall. ex Lindl.

Synthesis, Characterization, Antiglycation Evaluation, Molecular Docking, and ADMET Studies of 4-Thiazolidinone Derivatives.

The design and development of new small-molecule glycation inhibitors are essential for preventing various chronic diseases, including diabetes mellitus, immunoinflammation, cardiovascular, and neurodegenerative diseases. 4-Thiazolidinone or thiazolidine-4-one is a well-known heterocyclic compound with the potential to inhibit the formation of advanced glycation end products. In the present work, we report the synthesis and characterization of four new 5-arylidene 3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (1-4) compounds and their human serum albumin glycation inhibitory activity. One of the compounds 5-(2H-1,3-benzodioxol-5-ylmethylidene)-3-cyclopropyl-2-(phenylimino)-1,3-thiazolidin-4-one (3) showed potent inhibition in the synthesis of initial, intermediary, and final products of glycation reactions. Besides, conformational changes in the α-helix and β-sheet (due to hyperglycemia) were also found to be reversed upon the addition of (3). Experimental findings were complemented by computational [molecular docking, ADME/Tox, and density functional theory (DFT)] studies. The docking scores of the compounds were in order 1 > 3 > 2 > 4, indicating the importance of the polar group at the 5-arylidene moiety. The results of ADME/Tox and DFT calculations revealed the safe nature of the compounds with high drug-likeness and stability. Overall, we speculate that the results of this study could provide valuable insights into the biological activity of 4-thiazolidinones.

Aldose Reductase and Protein Glycation Inhibitory Activity of Dark Chocolate-Assisted Zinc Oxide Nanoparticles.

Introduction One of the most common health issues that the global population is dealing with is the associated complications of diabetes, which encompasses cataracts, peripheral neuropathy, vascular damage, impaired wound healing, retinal issues, and arterial wall stiffening. The present study is aimed to evaluate the effect of dark chocolate and its assisted zinc oxide nanoparticles against diabetes-associated complications. Materials and methods Zinc oxide nanoparticles were synthesized using commercially dark chocolate (DC-ZnO NP). The synthesized DC-ZnO NPs were evaluated against recombinant aldose reductase (AR) activity and the formation of advanced glycation end products (AGEs). Aminoguanidine and gallic acid were used as reference standards for AGE assay and sorbitol accumulation inhibition, respectively. Results The results of the present study showed that green synthesized DC-ZnO NP had a significant dose-dependent inhibitory activity on both AR and AGEs. The inhibitory activity was compared to that of quercetin and aminoguanidine, respectively. Conclusion Targeting the endogenous antioxidant systems like AGEs and AR enzymes seems to provide a promising therapeutic approach, thus concluding that ZnO-NP could be a promising agent for treating diabetes-related complications such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy that provide grounds for further clinical investigations and trials.

Antioxidant capacities of crude extract and protein glycation inhibitory activities of bioactive fractions of Arthrospira (Spirulina) platensis Gomont

Antioxidant capacities of crude extract and protein glycation inhibitory activities of bioactive fractions of Arthrospira (Spirulina) platensis Gomont

Recent Advances on Natural Aryl-C-glycoside Scaffolds: Structure, Bioactivities, and Synthesis-A Comprehensive Review.

Aryl-C-glycosides, of both synthetic and natural origin, are of great significance in medicinal chemistry owing to their unique structures and stability towards enzymatic and chemical hydrolysis as compared to O-glycosides. They are well-known antibiotics and potent enzyme inhibitors and possess a wide range of biological activities such as anticancer, antioxidant, antiviral, hypoglycemic effects, and so on. Currently, a number of aryl-C-glycoside drugs are on sale for the treatment of diabetes and related complications. This review summarizes the findings on aryl-C-glycoside scaffolds over the past 20 years, concerning new structures (over 200 molecules), their bioactivities-including anticancer, anti-inflammatory, antioxidant, antivirus, glycation inhibitory activities and other pharmacological effects-as well as their synthesis.

Structure analysis and tyrosinase, melanogenesis, α-glucosidase, and nonenzymatic glycation inhibitory activities of polymeric proanthocyanidins from the pulp of Crataegus pinnatifida Bge.

Crataegus pinnatifida Bge. is a worthwhile industrial crop for its extensive application in Chinese herbal pharmaceuticals, food, and other industries. In this study, proanthocyanidins were extracted from the pulp of Crataegus pinnatifida Bge., and the structure, antityrosinase, antimelanogenesis, anti-α-glucosidase, and anti-glycation activities of these compounds were systematically elucidated. The combined utilization of high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), and nuclear magnetic resonance (NMR) demonstrated that the proanthocyanidins were B-type procyanidin polymers consisting of epicatechin . These polymers were efficient, reversible, and competitive inhibitors of both tyrosinase and α-glucosidase with IC 50 values of 0.10 ± 0.01 mg/mL (for monophenolase), 0.16 ± 0.02 mg/mL (for diphenolase), and 0.50 ± 0.02 µg/mL, respectively. Moreover, the process of nonenzymatic glycation was also delayed by proanthocyanidins. Further cell assays suggested that these polymers strongly inhibited intracellular tyrosinase activity and melanogenesis and induced apoptosis in mouse melanoma cells. The results of circular dichroism (CD), molecular docking , and molecular dynamics (MD) consistently revealed that the inhibition of procyanidins on the two enzymes was primarily driven by hydrogen bonding and hydrophobic interactions, and the binding of epicatechin caused structural stretching and conformational modification of tyrosinase. Consequently, this study confirms novel tyrosinase, melanogenesis, α-glucosidase, and nonenzymatic glycation inhibitors, which might offer scientific evidence for potential applications in the cosmetics and pharmaceutical industries. • Proanthocyanidins can be produced industrially for a yield of 11.08%. • Various biological activities of proanthocyanidins enabled their wide applications. • Hydrogen bond and hydrophobic interaction loosened tyrosinase secondary structures. • Proanthocyanidins can reduce melanogenesis by down-regulating tyrosinase proteins.

Solubility Enhancement of Lawsone by Complexation with Beta Cyclodextrin

Abstract: Introduction: Lawsone is a phyto-constituent obtained from the leaves of the Lawsonia inermis. It has antibacterial, antifungal, antiviral, wound healing, antiparasitic, tuberculostatic, anti-fertility, analgesic, anti-inflammatory, enzyme inhibitory, nematicidal, anticoagulant, and protein glycation inhibitory activities. It has poor water solubility (hydrophobic), poor bioavailability, and poor dissolution characteristics. Aim: The purpose of this research is to improve the aqueous solubility of Lawsone by preparing the inclusion complexes of Lawsone with beta-cyclodextrin. Materials and Methods: Inclusion complexes of Lawsone were prepared by different methods such as physical mixture, kneading method and co-precipitation method. Characterization of the complexes were done by Fourier Transform Infrared (FTIR) spectroscopy and in vitro dissolution study. Differential scanning calorimetry (DSC), Nuclear Magnetic Resonance spectroscopy (NMR), and Powder X-Ray Diffraction (PXRD). were used to evaluate the co-precipitation technique inclusion complexes. Antimicrobial studies of complexes against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), and Pseudomonas aeruginosa (P. aeruginosa ) were done by colony counting method. Results: Phase solubility study revealed the molar ratio of Lawsone to betacyclodextrin in the complex is 1:1. At the third hour, the drug release was 64%, 78%, 93%, and 97% for pure drug, physical mixture, inclusion complexes formed by kneading technique and co-precipitation technique respectively. DSC, NMR, and PXRD confirmed the formation of complexes of Lawsone. The order of antibacterial activity of inclusion complexes was E. coli > B. subtilis > P. aeruginosa > S. aureus. Keywords: Lawsone, Beta-cyclodextrin, Inclusion complexes, Kneading method, Co-precipitation method.

Dual l-Carnosine/Aloe vera Nanophytosomes with Synergistically Enhanced Protective Effects against Methylglyoxal-Induced Angiogenesis Impairment.

Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of Aloe vera whole extract, and capability of l-carnosine, an endogenous dipeptide, in attenuating MGO's destructive activity, we examined whether application of a combination of l-carnosine and A. vera could be an effective way of synergistically weakening this reactive dicarbonyl's impaired angiogenic effects. Additionally, overcoming the poor cellular uptake and internalization of l-carnosine and A. vera, a nanophytosomal formulation of the physical mixture of two compounds was also established. Although l-carnosine and A. vera at whole studied combination ratios could synergistically enhance viability of human umbilical vein endothelial cells (HUVECs) treated with MGO, the 25:1 w/w ratio was the most effective one among the others (27 ± 0.5% compared to 12 ± 0.3 to 18 ± 0.4%; F (4, 15) = 183.9, P < 0.0001). Developing dual nanophytosomes of l-carnosine/A. vera (25:1) combination ratio, we demonstrated superiority of the nanophytosomal formulation in protecting HUVECs against MGO-induced toxicity following a 24-72 h incubation period (17.3, 15.8, and 12.4% respectively). Moreover, 500 μg/mL concentration of dual l-carnosine/A. vera nanophytosomes exhibited a superior free radical scavenging potency (63 ± 4 RFU vs 83 ± 5 RFU; F (5, 12) = 54.81, P < 0.0001) and nitric oxide synthesizing capacity (26.11 ± 0.19 vs 5.1 ± 0.33; F (5, 12) = 2537, P < 0.0001) compared to their physical combination counterpart. Similarly, 500 μg/mL dual l-carnosine/A. vera nanophytosome-treated HUVECs demonstrated a superior tube formation capacity (15 ± 3 vs 2 ± 0.3; F (5, 12) = 30.87, P < 0.001), wound scratch healing capability (4.92 ± 0.3 vs 3.07 ± 0.3 mm/h; F (5, 12) = 39.21, P < 0.0001), and transwell migration (586 ± 32 vs 394 ± 18; F (5, 12) = 231.8, P < 0.001) and invasion (172 ± 9 vs 115 ± 5; F (5, 12) = 581.1, P < 0.0001) activities compared to the physical combination treated ones. Further confirming the proangiogenic activity of the dual l-carnosine/A. vera nanophytosomes, a significant shift toward expression of proangiogenic genes including HIF-1α, VEGFA, bFGF, KDR, and Ang II was reported in treated HUVECs. Overall, dual l-carnosine/A. vera nanophytosomes could be a potential candidate for attenuating type II DM-associated microvascular complications with an impaired angiogenesis background.

Vanillic acid-Zn(II) complex: a novel complex with antihyperglycaemic and anti-oxidative activity.

Our aim was to synthesize, characterize and evaluate the antihyperglycaemic and anti-oxidative properties of a new Zn(II) complex of vanillic acid. The complex was synthesized using ZnSO4.7H2O and vanillic acid as precursors. NMR and FTIR techniques were used to characterize the synthesized complex. The cytotoxicity of the complex was measured. The antihyperglycemic and anti-oxidative properties of the complex were evaluated using in vitro, cell-based and ex vivo models and compared with those of its precursors. Zn(II) coordinated with vanillic acid via a Zn(O6) coordination, with the complex having three moieties of vanillic acid. The radical scavenging, Fe3+ reducing and hepatic antilipid peroxidative activity of the complex were, respectively, 2.3-, 1.8- and 9.7-folds more potent than vanillic acid. Complexation increased the α-glucosidase and glycation inhibitory activity of vanillic acid by 3- and 2.6-folds, respectively. Zn(II) conferred potent L-6 myotube (EC50 = 20.4 μm) and muscle tissue (EC50 = 612 μm) glucose uptake effects on vanillic acid. Cytotoxicity evaluation showed that the complex did not reduce the viability of L-6 myotubes and Chang liver cells. The data suggest that Zn(II)-vanillic acid complex had improved bioactivity relative to vanillic acid. Thus, Zn(II) may be further studied as an antihyperglycaemic and anti-oxidative adjuvant for bioactive phenolic acids.

Biotransformed Antioxidant isoflavone extracts present high-capacity to attenuate the in vitro formation of advanced glycation end products

ABSTRACT Advanced glycation end products (AGEs) are toxic with a high capacity to cause damages to health, mainly associated with diabetes complications. In this study, soybean isoflavone extracts were subjected to different biotransformation processes: Lactobacilli fermentation, Enzymatic and Enzymatic followed by fermentation, in order to improve their antioxidant capacity and bioactive isoflavone content. The effects of the biotransformation processes on total phenolic content, antioxidant activities, and isoflavone profile were evaluated. Analyses of antiglycation activity of the isoflavones extracts were evaluated by glycation models in vitro. The results showed that all bioprocesses increased the aglycone content, as well as the antioxidant capacity by about 2.5 times using ORAC and 1.6 times using FRAP assays. The results were superior for enzymatic biotransformation followed by fermentation. All processes showed about 24,33% to 57,33% of anti-glycationt capacity, indicating that biotransformation improved the bioactivity of isoflavones extracts for glycation inhibitory activity, as well as the associated e antioxidant capacity.

Chemoprofiling of Artocarpus camansi Blanco. and Artocarpus lakoocha Wall. ex. Roxb. and its antidiabetic potential for modulation of digestive enzymes, protein glycation and glucose uptake in L6 myotubes

Acetone extract of the stem bark of Artocarpus camansi and Artocarpus lakoocha afforded 14 compounds. Herein, we report the compounds 3, 8, 9, 10, 11, 12 and 13 for the first time from these species. The structures were elucidated on the basis of various spectroscopic analyses including IR, 1D and 2D NMR, and HRMS data. All the isolated compounds were tested for α-glucosidase, α-amylase and glycation inhibitory activity. Oxyresveratrol displayed prominent IC50 value of 37.38 ± 1.11 µM in -glucosidase inhibitory assay. Compound 3, 4 and 8-13 exhibited moderate -glucosidase inhibitory activity. The effect of glucose uptake performed by 2-NBDG in L6 muscle cells using fluorescent microscope and flow cytometry. The compounds E-resveratrol (1), artobiloxanthone (11) and artonol B. (13) showed glucose uptake of 32.2 %, 32.9 % and 33.5 % respectively.

Study on the active polyphenol constituents in differently colored Rubus Chingii Hu and the structure-activity relationship of the main ellagitannins and ellagic acid

Color is considered an index to evaluate the quality of the unripe fruit of Rubus chingii Hu in China. This study compared the contents of the active polyphenolic constituents in unripe differently colored fruits. The data showed that there were significant differences between the yellow fruit (YF) and green fruit (GF) in the composition of ellagitannins (ETs) and ellagic acid (EA). Then, the structure-activity relationship of the main ellagitannins (lambertianin A, sanguiin H-6, casuarictin) and ellagic acid in unripe fruits were investigated by the antioxidant activities assay, non-enzymatic glycation inhibitory activity assay and glucose uptake assay in L6 cells. The results showed that the number of hydroxyl groups and galloyl configuration at the glucose C-1 significantly affected the activity of ellagitannins. However, ellagic acid, which had fewer hydroxyl groups, exhibited the highest bioactive properties. Moreover, the fluorescence quenching analysis and molecular docking results demonstrated that ellagitannin was a concentration-dependent antiglycation compound. This study suggested that EA and ETs had different action mode and the content of ETs was an important factor influencing the unripe fruits of Rubus chingii Hu.

Alpha amylase, alpha glucosidase and glycation inhibitory activity of Moringa oleifera extracts

Moringa oleifera is a source of food, shelter and traditional medicine for many people in developing countries. It is an exceptional source of vitamins, minerals, amino acids, lipids, carotenoids, flavonoids, sterols and phenolics. Owing to its diverse nutritional and phytochemical composition, it is widely consumed and used in therapeutics. In this study, the aqueous, methanol, hexane and ethyl acetate extracts of M. oleifera seeds, leaves and roots were assessed for in vitro α-amylase, α-glucosidase and glucose-induced bovine serum albumin glycation inhibition. Findings indicate that methanol and hexane leaves extracts demonstrated highest α-amylase inhibitory activity (IC50 = 8.217 and 9.397 mg/ml respectively), though the activities were lower than that of acarbose (IC50 = 0.036 mg/ml). In contrast, hexane root extract exhibited optimal α-glucosidase inhibition and antiglycation effect (IC50 = 0.382 and 0.772 mg/ml, respectively). The extract activity was higher than that of acarbose (IC50 = 0.884 mg/ml), but lesser than rutin (IC50 = 0.199 mg/ml); which were the control for α-glucosidase inhibition and antiglycation studies respectively. In conclusion, suggesting its potentials in regulating postprandial blood glucose, and attenuating the production/accumulation of advanced glycation end product. Thus, M. oleifera extracts exhibited promising antidiabetic activity.

Dicoma anomala (Sond.) abates glycation and DPP-IV activity and modulates glucose utilization in Chang liver cells and 3T3-L1 adipocytes

Dicoma anomala (Sond.) is known for its folkloric application in the treatment diabetes, but with few scientific evidences. This study reported the antidiabetic potential and possible mode of actions of this plant. The phenolic content; α-glucosidase, DPP-IV and glycation inhibitory activities and glucose utilization and adipocyte differentiation modulatory activities of D. anomala root extracts (hexane, DCM, DCM:MeOH 50:50 and MeOH) were determined. The DCM:MeOH extract had the highest phenolic content. Same extract exhibited the most potent DPP-IV (IC50 = 164.96 μg/mL) and glycation (70.3% at 5 μg/mL) inhibitory effects. The DCM:MeOH and MeOH extracts showed the most potent modulatory effects on glucose utilization, while the DCM:MeOH showed the most potent adipocyte differentiation (AD50; extract concentration causing 50% adipocyte differentiation = 68.55 μg/mL) in 3T3-L1 adipocytes. The glucose utilization modulatory effect of the DCM:MeOH extract in Chang liver cells was comparable to that of metformin. Lupeol and quercetin were the main bioactive compounds was identified in DCM:MeOH and MeOH. The DCM:MeOH extract was non-cytotoxic at effective concentrations. D. anomala root extract may exert glycemic control by inhibiting DPP-IV activity and glycation process and modulating glucose uptake.

Isolation and characterization of resveratrol oligomers from the stem bark of Hopea ponga (Dennst.) Mabb. And their antidiabetic effect by modulation of digestive enzymes, protein glycation and glucose uptake in L6 myocytes

Ethnopharmacological relevanceHopea ponga (Dennst.) Mabb. Is used in traditional herbal formulations for diabetes complications. The aim of this study is to evaluate the antidiabetic effect of extracts and compounds from H. ponga. Materials and methodsSilica gel column chromatography was performed to identify various chemical components of the plant extract. Different extracts of H. ponga and isolated compounds were screened for their antidiabetic effect by modulation of digestive enzymes and protein glycation. The effect of glucose uptake by the compounds and the pathways through which the compounds mediate the glucose uptake potential were confirmed by fluorescent microscopy, flow cytometry and western blot analysis. ResultsAcetone and ethanol extracts of the stem bark of Hopea ponga (Dennst.) Mabb. Afforded six resveratrol oligomers namely, E-resveratrol (1), (−)-ε-viniferin (2), (−)-α-viniferin (3), trihydroxyphenanthrene glucoside (THPG) (4), vaticaphenol A (5), (−)-hopeaphenol (6), along with four phytosterols. The structures were determined on the basis of spectroscopic analyses including nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry (HRMS) data. Compounds 1–5 and 7–10 were tested for their α-glucosidase, α-amylase and glycation inhibitiory activities. All the resveratrol oligomers (1–5) showed prominent α-glucosidase inhibition with IC50 values, 12.56 ± 1.00, 23.98 ± 1.11, 7.17 ± 1.10, 31.74 ± 0.42 and 16.95 ± 0.39 μM, respectively. Molecular docking studies also supported the observed α-glucosidase inhibition. Compound 3 displayed IC50 values of 4.85 ± 0.06 and 27.10 ± 0.04 μM in α-amylase and glycation inhibitory assays activity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed that the compounds 3 and 4 were found to be less toxic at a concentration of 100 μM (<10%) and 25 μM (<20%), respectively. The effect of glucose uptake performed by 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in L6 myoblast were measured by fluorescent microscopy and flow cytometry. The compounds 3 and 4 showed 2-NBDG uptake of 49.6% and 38.8% respectively. By examining the molecular pathway through which the compounds elicit their glucose uptake potential, it was observed that both the compounds mainly act via AMPK pathway. ConclusionThis is the first report on the isolation of compounds from H. ponga. Altogether, the results of this study reveal the antidiabetic effects of H. ponga extracts and isolated compounds promoting traditional use of this plant in the treatment of diabetes.

α-Glucosidase and glycation inhibitory activities of Rumex lunaria leaf extract: a promising plant against hyperglycaemia-related damage

Rumex lunaria L. is a Canarian medicinal plant, belonging to Polygonaceae. The potential antidiabetic activity of the methanolic extract of the leaves was investigated. For this purpose, the inhibition of α-glucosidase and albumin glycation by the extract was studied. Further, the anti-radical activity and the phytochemical composition were detected. The reduction of α-glucosidase activity was significant from 3 µg/mL, while the BSA glycation inhibition started from 100 µg/mL. Moreover, the extract exhibited a significant free-radical scavenger activity. Its phytochemical characterization showed the presence of carotenoids, phenolic and flavonoid compounds, whereas anthraquinones were not detected. C-flavonoid glycosides were identified and quercetin-O-hexoside-O-deoxyhexoside was the most detected (22.67 ± 0.02 mg/g). The findings indicate that the methanolic R. lunaria leaf extract has significant anti-α-glucosidase, anti-radical and anti-glycation activities. This research is the first showing the potential antidiabetic activity of R. lunaria.

Glycation Inhibitory and Antioxidative Activities of Ergothioneine

Glycation Inhibitory and Antioxidative Activities of Ergothioneine

Stem bark exudate (resin) of Araucaria cunninghamii Aiton ex D. Don (hoop pine) abates glycation, α-glucosidase and DPP-IV activity and modulates glucose utilization in Chang liver cells and 3T3-L1 adipocytes

Araucaria cunninghamii (hoop pine) is known for its traditional medicinal uses. The stem bark exudes resin, which possess anti-microbial properties, but its anti-diabetic potentials remain unknown. We investigated the anti-diabetic potentials and possible mode of actions of the stem bark exudate (resin) of A. cunninghamii. Phenolic content; α-glucosidase, DPP-IV and glycation inhibitory activities and glucose utilization and adipocyte differentiation modulatory activities of different solvent extracts (HEX, DCM, MeOH and DCM:HEX) of A. cunninghamii stem bark exudate were determined. Phenolic content did not differ among extracts. Alpha glucosidase inhibition of MeOH extract (48.5%) was twice (p < .05) that of other extracts (24.2%–26.6%), and comparable to that of acarbose (48.7%). DPP-IV inhibition of HEX, DCM and MeOH extracts was double (p < .05) that of DCM:HEX extracts. All extracts dose-dependently (5 and 50 μg/mL) inhibited glycation and significantly (p < .05) modulated glucose utilization in Chang liver cells. In 3T3-L1 adipocytes, glucose utilization modulatory effect of MeOH extract was comparable to that of insulin. 3T3-L1 adipocytes differentiation was not altered by all extracts. Arachidonic acid and methyl oleate were identified by GC–MS in the MeOH extract. In silico docking showed that GLUT-4 (binding energy = −10.5 kcal mol−1) and α-glucosidase (binding energy = −8.5 kcal mol−1) are possible molecular targets of these compounds, respectively. Data suggest that the glucose uptake modulatory effect of A. cunninghamii stem bark exudate in adipocytes may be via GLUT-4 modulation, but independent of PPARγ. A. cunninghamii stem bark exudate showed great potentials for further investigation in the management of diabetes and its complications.

South African traditional herbal formulation inhibits α-glucosidase, DPP-IV and glycation activities, and modulates glucose utilisation in Chang liver cells and 3T3-L1 adipocytes

In South Africa, herbal mixture preparations are often used as alternative treatments for various diseases including diabetes. Most of the herbal mixture preparations have not been well investigated and regulated. The aim of this study was to evaluate anti-diabetic potentials and possible mode of actions of a South African herbal formulation locally called “Mabaso”. It is prepared from three plants, namely Sclerocarya birrea (A. Rich.) Hochst, Opuntia ficus-indica (L.) Mill. and Solanum pimpinellifolium L. The phenolic and flavonoid contents, α-glucosidase, DPP-IV and glycation inhibitory activities as well as glucose utilisation and adipocyte differentiation modulatory activities of herbal mixture was evaluated for the first time. The HPLC fingerprints of potent extracts were also determined. The DCM:MeOH extract showed the highest phenolic content. Same extract exhibited the most potent α-glucosidase, DPP-IV (73.51% at 50 μg/ml) and glycation (62.5% at 5 μg/ml) inhibitory activities. DCM:MeOH and MeOH extracts appreciably enhanced glucose utilisation in 3T3-L1 adipocytes and Chang liver cells respectively. Herbal mixture extracts enhanced (p < .05) adipocyte differentiation in 3T3-L1 adipocytes. Data suggest that the studied herbal formulation may potentiate anti-hyperglycemic effects via inhibiting α-glucosidase, DPP-IV and glycation activities as well as enhancing glucose utilisation and/or adipocyte differentiation. Thus, this herbal preparation may be an interesting candidate for further investigation on their ameliorative potentials against diabetes and its complications using appropriate animal models.

Inhibition of advanced glycation end products by Punica granatum Linn. leaves and its antioxidant activity

Advanced glycation end products (AGEs) are the consequent products by virtue of non-enzymatic reaction of reducing sugars with amino groups present either in lipids, nucleic acids or proteins. Lately AGEs have been embroiled in the inception of diabetes induced complications. In Ayurveda, Punica granatum is contemplated as “a pharmacy unto itself”. Punica granatum leaves have been stated to have anti-diabetic activity. The purpose of the existing study was to determine the anti-glycation potential of methanolic extract of Punica granatum leaves (MPGL) and investigate the fundamental mechanisms in discouraging the glycation process. Antioxidant activity of MPGL was estimated by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (3-ethyl-benzothiazoline-6-sulfonic acid) radical scavenging assays. Both MPGL and aminoguanidine were evaluated against the formation of AGEs. Antiglycation activity was evaluated by determining the fluorescence intensity of AGEs and formation of fructosamine. Protein oxidation in the glycation process was determined by evaluating the protein carbonyl content and thiol group. MPGL demonstrated IC50 value of 15.602 ± 0.296 and 724.323 ± 16.451 µg/ml for the DPPH and ABTS radical scavenging assays respectively. Current study revealed that MPGL had cogent effects on the in vitro formation of AGEs. MPGL decreased fructosamine level and significantly counteracted the oxidative damage of protein by curbing protein carbonyl content and impeding the loss of thiol group. The anti-glycation activity was farther cogent than the glycation inhibitory activity attained using the standard drug, aminoguanidine. Thereupon, MPGL presents to be more encouraging to be emerged as an competent AGE inhibitor.