Antidiabetic Agents Research Articles

Acyl pyrazole sulfonamides as new antidiabetic agents: synthesis, glucosidase inhibition studies, and molecular docking analysis.

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14µM), with IC50 values ranging from 1.13 to 28.27µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).

Effect of SGLT2 Inhibitors on Post-PCI Outcomes after Acute Myocardial Infarction in Diabetic Patients: A Systematic Review and Meta-Analysis

Background: Acute myocardial infarction (AMI) is related with poor outcomes in patients with diabetes mellitus (DM). Whether diabetic patients with AMI undergoing percutaneous coronary intervention (PCI) benefit from sodium–glucose cotransporter 2 inhibitors (SGLT2i) in terms of cardiovascular mortality, myocardial damage, and left ventricular function is unclear. Methods: Through a comprehensive search in PubMed, EMBASE, and Web of science databases from January 2018 to September 2023, randomized controlled trials were performed to compare SGLT2i with other oral antidiabetic medications in diabetic patients with AMI undergoing PCI. Cardiovascular mortality constituted the primary outcome. Secondary outcomes were high-sensitivity troponin I (hs-TnI) levels, left ventricular ejection fraction (LVEF), and contrast-induced acute kidney injury (CI-AKI). Results: SGLT2i significantly reduced cardiovascular mortality risk versus other antidiabetic agents (hazard ratio (HR): 0.35, 95% confidence interval (CI): 0.21–0.58, p < 0.0001). SGLT2i also lowered hs-TnI levels across all time points (mean difference: –2931 ng/L, p < 0.001). After adjustment for publication bias, this difference was no longer significant. However, peak hs-TnI levels remained significantly lower with SGLT2i (mean difference: –3836 ng/L, p < 0.001). Finally, SGLT2i improved LVEF versus comparators, with a mean difference of –5.00% (95% CI: –6.69 to –3.31, p < 0.001) at hospital discharge. SGLT2i was also associated with 60% lower odds of CI-AKI (odds ratio (OR): 0.40, 95% CI: 0.22–0.75, p = 0.004). Conclusions: Compared with other antidiabetic medications, SGLT2i may lower cardiovascular mortality, infarct size, and prevent left ventricle (LV) systolic dysfunction in diabetic patients with AMI undergoing PCI. The use of SGLT2i in this high-risk group is supported by these findings.

Design, synthesis, molecular dynamic simulation, DFT analysis, computational pharmacology and decoding the antidiabetic molecular mechanism of sulphonamide-thiazolidin-4-one hybrids

In search of novel antidiabetic agents, the study was framed to hybridize and synthesize molecules based on scaffolds of benzenesulfonamide and thiazolidine-4-one, efficiently synthesized (6a-6h) and structurally characterized by FTIR, 1H NMR 13C NMR and HRMS spectroscopy. The antidiabetic activity was assessed based on α-amylase inhibition, glucose uptake assay and PPAR-γ transcription factor assay. Compound 6b (4-(2-((E)-5-((Z)-2-hydroxybenzylidene)-4-oxo-2-(phenylimino) thiazolidin-3-yl) ethyl) benzenesulfonamide) demonstrated promising activity toward α-amylase inhibition having IC50 value of 29.51±1.35 µg/ml. A glucose uptake assay was performed for compounds (6a-6h) to assess the capacity of glucose uptake. Among them, Compound 6b exhibits notable glucose uptake with 88.71% in the yeast cell line. To support the glucose uptake findings of compound 6b, expression of PPAR-γ transcription factor was measured of compound 6b as compared to pioglitazone. Furthermore, induced fit docking was carried out to predict the refined pose of synthesized compounds in the α-amylase binding pocket. MD simulation studies confirmed the stability of compound 6b in the α-amylase binding pocket. Molecules were geometrically optimized by DFT theory using B3LYP 6–31 G (d, p**) basis set, and electronic properties were studied. Network pharmacology analysis for compound 6b identified key pathways involved in T2DM and postprandial hyperglycemia like PI3K-Akt pathway, Type II diabetes mellitus pathway metabolic pathway, and digestion of dietary carbohydrates pathway. These findings provide better insights into further developing benzenesulfonamide-based thiazolidin-4-one hybrids as antidiabetic agents.

Drosophila melanogaster as a model organism for diabetes II treatment by the ethyl acetate fraction of Atriplex halimus L.

Type 2 diabetes (T2D) is the most common metabolic disorder. The undesirable effects of synthetic drugs demand a search for safe antidiabetic agents. This study aimed to assess the antidiabetic activity of different fractions of Atriplex halimus (petroleum ether 60-80, methylene chloride, ethyl acetate, and n-butanol) using Drosophila melanogaster larvae. Titers of total glucose and trehalose, as well as larval weight, were measured and compared with those of control and diabetic larvae. The expression of Drosophila insulin-like peptides (DILP2 and DILP3) and adipokinetic hormone (AKH) was evaluated. The results revealed a significant increase in total glucose, trehalose, and a decrease in body weight in the larvae fed a high-sugar diet compared with those in the control. When larvae fed diets containing the tested fractions, the total glucose and trehalose decreased to the control level, and the body weight increased. DILP2, DILP3, and AKH exhibited significant decreases upon treatment with A. halimus ethyl acetate. Metabolomic profiling of the ethyl acetate fraction of A. halimus revealed the presence of flavonoids and flavonoid glycosides. After docking screening to predict the most powerful moiety, we discovered that flavonoid glycosides (especially eriodictyol-7-O-neohesperidoside) have a greater affinity for the pocket than the other moieties. The results indicated the therapeutic activity of the A. halimus ethyl acetate fraction against induced T2D in Drosophila larvae. The antidiabetic activity may be attributed to flavonoids, which are the main components of the A. halimus ethyl acetate fraction.

Comparative Phytochemical, In-vitro Anti-Hyperglycemic Activities of Napoleona vogelii Hook & Planch Stem Bark and Cassia occidentalis L. Root Extracts

This work investigated the comparative phytochemical, proximate and anti-hyperglycemic activities of stem bark of Napoleonaea vogelii and root of Cassia occidentals extracts. Stem bark and N. vogelii root of C. occidentalis were cold extracted with methanol, ethyl acetate, and n-hexane. The extracts were subjected to proximate, phytochemical analyses and anti-hyperglycemic assays. The result of proximate analysis revealed that stem bark of N. vogelii was made up of 40.28 ± 0.49 % crude fibre, 37.05 ± 0.05 % carbohydrates, 7.45 ± 0.45 % protein and more than 6.00 % oil content. whereas 22.33±0.08 % crude fibre, 44.70± 0.93 % carbohydrates, 10.72± 0.05 % protein and 11.00± 0.00 % oil contents in roots of C. occidentalis. Alkaloids and terpenoids were present in all the extracts of N. vogelii and C. occidentalis. Flavonoids were also found in all extracts of N. vogelii, whereas tannins and glycosides were also found in all extracts of C. occidentalis. In vitro antidiabetic screening of the methanol extracts indicated that both plants showed a good concentration-dependent percentage glucose uptake. In all concentrations, extracts of C. occidentalis exhibited better glucose uptake than N. vogelii extracts. comparable to the activity of the standard drug- metronidazole (68.44±0.00 %), From 0.10 – 0.50 mg/mL, the methanol extracts of both plants also showed a dose-dependent α-amylase inhibitory effect. But the inhibition decreased as the concentration was increased to 1.00 mg/mL. At 0.50 mg/mL, C. occidentalis and N. vogelii showed percentage inhibitory effect of 50.02±0.035 and35.61±0.01. Both plants’ extracts showed good anti-hyperglycemic activity, which may be due to the presence of alkaloids, terpenoids, saponins and tannins in the extracts, validating the folkloric use of both plants in the treatment of diabetes, and thus are good anti-diabetic agents.

Aloe juvenna Brandham & S.Carter as α-Amylase Inhibitor and Hypoglycaemic Agent with Anti-inflammatory Properties for Diabetes Management.

Despite Aloe's traditional use, Aloe juvenna Brandham & S.Carter is poorly characterized. Other Aloes are known for their antidiabetic activity. This study describes the antidiabetic potentials and phytoconstituents of the A. juvenna leaves methanolic extract (AJME). Twenty-six phytoconstituents of AJME were described using HPLC/MS-MS. Lupeol and vitexin were isolated using column chromatography. The antidiabetic activity of AJME was investigated using an in vivo high-fat diet/streptozotocin-induced diabetic rat model and in vitro α-glucosidase and α-amylase inhibitory activity assays. AJME demonstrated its α-amylase inhibitory activity (IC50=313±39.9 ppm) with no effect on α-glucosidase. In vivo, AJME dose-dependently improved hyperglycaemia in a high-fat diet/streptozotocin-induced diabetic rat model. Notably, the higher dose (1600 mg/kg) of AJME significantly downregulated serum interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-1 genes, suggesting its anti-inflammatory effect. These findings indicate AJME's potential as a significant antidiabetic agent through its α-amylase inhibition, hypoglycaemic, and anti-inflammatory properties.

Purification of exopolysaccharide produced from Lactobacillus spp. using ionic-liquid as adjuvant in alcohol/salt-based aqueous two-phase system for its antidiabetic properties

Diabetes is a chronic, metabolic disease characterized by hyperglycemia resulting from either insufficient insulin production or impaired cellular response to insulin. Exopolysaccharides (EPS) produced by Lactobacillus spp. demonstrated promising therapeutic potential in terms of their anti-diabetic properties. Extraction and purification of EPS produced by Lactobacillus acidophilus and Limosilactobacillus reuteri were performed using ethanol precipitation, followed by alcohol/salt based aqueous two-phase system (ATPS). The purification process involved ethanol precipitation followed by an alcohol/salt-based ATPS. The study systematically investigated various purification parameters in ATPS, including ethanol concentration, type and concentration of ionic liquid, type and concentration of salt and pH of salt. Purified EPS contents from L. acidophilus (63.30 μg/mL) and L. reuteri (146.48 μg/mL) were obtained under optimum conditions of ATPS which consisted of 30 % (w/w) ethanol, 25 % (w/w) dipotassium hydrogen phosphate at pH 10 and 2 % (w/w) 1-butyl-3-methylimidazolium octyl sulfate. The extracted EPS content was determined using phenol sulphuric acid method. In α-amylase inhibition tests, the inhibitory rate was found to be 92.52 % (L. reuteri) and 90.64 % (L. acidophilus), while in α-glucosidase inhibition tests, the inhibitory rate was 73.58 % (L. reuteri) and 68.77 % (L. acidophilus), based on the optimized parameters selected in ATPS. These results suggest that the purified EPS derived from the postbiotics of Lactobacillus spp. hold promise as potential antidiabetic agents.

Antidiabetic effectiveness of Phyllanthus niruri bioactive compounds via targeting DPP-IV.

Phyllanthus niruri Linn. (Euphorbiaceae) is a small herb and is categorised as one of the rich medicinal plants throughout the world. This study aimed to evaluate the P. niruri L. whole plant extract (PNE) for secondary metabolite assay (total phenolic and terpenoid content) followed by the potential antioxidant activity (ABTS diammonium salt radical assay, DPPH· activity, superoxide anion (O2-) radicals' assay, and nitric oxide (NO) radical generation) and antidiabetic activity in vivo and in vitro in streptozotocin (STZ) induced albino mice. PNE showed good scavenging activity with a value of 286.45 ± 6.55 mg TE/g and 194.54 ± 4.64 mg TE/g in ABTS and DPPH assays respectively. In the superoxide anion assay, the PNE caused a dose-dependent inhibition at the lowest IC25 value of 0.17 ± 0.00 mg/mL compared to ascorbic acid (IC25 of 0.25 ± 0.02 mg/mL). The scavenging ability of PNE against nitric oxide showed an IC25 of 1.13 ± 0.04 mg/mL compared to ascorbic acid (IC25 4.78 ± 0.09 mg/mL). Unlike diabetic control mice, the PNE-treated diabetic mice presented significant amelioration of glycaemia and lipid dysmetabolism. Phytochemicals like Astragalin, Gallocatechin, Ellagic acid, Gallic acid, Brevifolin carboxylic acid, Phyllnirurin, and Hypophyllanthin showed significant docking score (> -4) of inhibitory potential with DPP-IV protein. Results indicated that PNE phytochemicals could be a promising antidiabetic agent by targeting DPP-IV.

Exploring the multifaceted bioactivities of Lavandula pinnata L. essential oil: promising pharmacological activities.

Introduction: This study investigates the biological activities of Lavandula pinnata essential oil (LPEO), an endemic lavender species from the Canary Islands, traditionally used in treating various ailments. Methods: LPEO was extracted by hydrodistillation and analyzed using GC-MS. Antioxidant activity was assessed by DPPH radical scavenging and total antioxidant capacity assays. Antimicrobial activity was evaluated by disc diffusion, MIC, MBC, and MFC determination against bacterial (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa) and fungal (Candida glabrata, Rhodotorula glutinis, Aspergillus niger, Penicillium digitatum) strains. Antidiabetic and anti-gout potential were investigated through α-amylase, α-glucosidase, and xanthine oxidase inhibition assays. Antityrosinase activity was determined using a modified dopachrome method. Cytotoxicity was assessed by MTT assay against breast (MCF-7, MDA-MB-468), liver (HepG2), colon (HCT-15) cancer cells, and normal cells (PBMCs). Results and discussion: LPEO exhibits potent antiradical activity (IC50 = 148.33 ± 2.48μg/mL) and significant antioxidant capacity (TAC = 171.56 ± 2.34μg AA/mg of EO). It demonstrates notable antibacterial activity against four strains (Staphylococcus aureus, Micrococcus luteus, Escherichia coli, and Pseudomonas aeruginosa) with inhibition zones ranging from 18.70 ± 0.30mm to 29.20 ± 0.30mm, along with relatively low MIC and MBC values. LPEO displays significant antifungal activity against four strains (Candida glabrata, Rhodotorula glutinis, Aspergillus niger, and Penicillium digitatum) with a fungicidal effect at 1mg/mL, surpassing the positive control (cycloheximide), and MIC and MFC values indicating a fungicidal effect. It exhibits substantial inhibition of xanthine oxidase enzyme (IC50 = 26.48 ± 0.90μg/mL), comparable to allopurinol, and marked inhibitory effects on α-amylase (IC50 = 31.56 ± 0.46μg/mL) and α-glucosidase (IC50 = 58.47 ± 2.35μg/mL) enzymes.The enzyme tyrosinase is inhibited by LPEO (IC50 = 29.11 ± 0.08mg/mL). LPEO displays moderate cytotoxic activity against breast, liver, and colon cancer cells, with low toxicity towards normal cells (PBMC). LPEO exhibits greater selectivity than cisplatin for breast (MCF-7) and colon (HCT-15) cancer cells but lower selectivity for liver (HepG2) and metastatic breast (MDA-MB-468) cancer cells. These findings suggest the potential of LPEO as an antioxidant, antimicrobial, anti-gout, antidiabetic, and anticancer agent.

Harnessing silk fibroin microparticles for metformin delivery: A novel approach to treating corneal neovascularization

Corneal neovascularization (CV) poses significant challenges in ophthalmology, often leading to impaired vision and discomfort. Silk fibroin microparticles have emerged as promising candidates for drug delivery applications, owing to their biocompatibility, biodegradability, and controlled release characteristics. In the current research, metformin-loaded silk microparticles were developed, and their potential for treating corneal neovascularization was evaluated. Silk microparticles were prepared using silk fibroin and polyvinyl alcohol (PVA) at various weight ratios, facilitating phase separation to create a porous structure conducive to drug loading. Metformin (MT), a widely used antidiabetic agent with potential anti-angiogenic properties, was incorporated into the silk microparticles at different concentrations. The formulation termed TB (0.3 % MT loaded Microparticles) emerged as the most promising candidate was identified through comprehensive in vitro evaluations. In in vitro cytotoxicity studies, it was determined that all formulations provided cell viability above 80%, however, in permeability studies and encapsulation efficiency studies, TB was determined to be more effective than other formulations. TB demonstrated a particle size of approximately 8.9 ± 3.6 μm and an encapsulation efficiency of 96.3 ± 2.1%. In vitro release studies revealed that TB exhibited a burst release of 62% within the initial two days, followed by sustained release over a period of 14 days, consistent with Peppas-Sahlin kinetics. Mathematical modeling further corroborated the diffusion mechanism underlying drug release from TB microparticles. In vivo studies on rats and histochemical analyzes on corneas showed that TB exhibited efficacy comparable to dexamethasone, a standard treatment for CV, despite being administered once daily. Histological analyses of corneal tissues revealed reduced neovascularization and inflammation in the TB-treated group, underscoring its therapeutic potential. Overall, our findings highlight the promise of metformin-loaded silk fibroin microparticles as a novel therapeutic approach for managing CV, offering sustained drug release and enhanced efficacy in treating this challenging ocular condition.

Antidiabetic Properties of the Root Extracts of Dandelion (Taraxacum officinale) and Burdock (Arctium lappa).

Several preclinical studies suggest the potential of edible plants in controlling blood sugar levels and stabilizing diet. The goals of the study were to examine, analyze, and describe whether there are chemical compounds in dandelion and burdock roots that could have antidiabetic properties. The 70% ethyl alcohol and lyophilizate extracts (AE and LE, respectively), were used, and analyses were carried out on their total polysaccharide (TP), total phenolic content (TPC), tannin, and inulin. The antioxidant activity of extracts was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and hypoglycemic properties were based on α-amylase activity. Liquid chromatography-mass spectrometry was used for the tentative identification of the chemical components. Qualitative techniques confirmed the presence of inulin in both roots. Analysis of TPC, tannin content, DPPH assay, and α-amylase activity revealed higher values for burdock compared to dandelion. However, dandelion exhibited higher TP content. Burdock contained a small amount of tannin, whereas the tannin content in dandelion was insignificant. All LE consistently exhibited higher values in all analyses and assays for all roots compared to AE. Despite burdock root showing overall better results, it is uncertain whether these plants can be recommended as antidiabetic agents without in vivo studies.

Exploring Type II Diabetes Inhibitors from Genus Daphne Plant-species: An Integrated Computational Study.

Plant species of the genus Daphne clasps a historical background with a potential source of bioactive phytochemicals such as flavonoids and daphnodorins. These compounds manifest a significant chemotaxonomic value in drug discovery. Their flair comprehensive pharmacological, phytochemical, biological, catalytic, and clinical utilities make them exclusively unique. This study was conducted to investigate the optimization and structure-based virtual screening of these peculiar analogs. The majority of the active constituents of medicines are obtained from natural products. Previously, before the invention of virtual screening methods or techniques, almost 80% of drugs were obtained from natural resources. Comparing reported data to drug discovery from 1981 to 2007 signifies that half of the FDA-approved drugs are obtained from natural resources. It has been reported that structures of natural products that have particularities of structural diversity, biochemical specification, and molecular properties make them suitable products for drug discovery. These products basically have unique chiral centers which increase their structural complexity than the synthesized drugs. This work aimed to probe the use of daphnodorins analogs for the first time as antidiabetic inhibitors based on significant features and to determine the potential of daphnodorin analogs as antidiabetic inhibitors through computational analysis and structure-based virtual screening. A dataset of 38 compounds was selected from different databases, including PubChem and ZINC, for computational analysis, and optimized compounds were docked against various co-crystallized structures of inhibitors, antagonists, and receptors which were downloaded from PDB by using AutoDock Vina (by employing Broyden-Fletcher-Goldfarb-Shanno method), Discovery studio visualizer 2020, PYMOL (Schrodinger). Docking results were further validated by Molecular dynamic simulation and MM-GBSA calculation. Quantitative structure-activity relationship (QSAR) was reported by using Gaussian 09W by intimating Density Functional Theory (DFT). Using this combination of multi-approach computational strategy, 14 compounds were selected as potential exclusive lead compounds, which were analyzed through ADMET studies to pin down their druglike properties and toxicity. At significant phases of drug design approaches regular use of molecular docking has helped to promote the separation of important representatives from 38 pharmaceutically active compounds by setting a threshold docking score of -9.0 kcal/mol which was used for their exposition. Subsequently, by employing a threshold it was recognized that 14 compounds proclaimed this threshold for antidiabetic activity. Further, molecular dynamic simulation, MM-GBSA, ADMET, and DFT results screened out daphnegiralin B4 (36) as a potential lead compound for developing antidiabetic agents. Our analysis took us to the conclusion that daphnegiralin B4 (36) among all ligands comes out to be a lead compound having drug-like properties among 38 ligands being non-carcinogenic and non-cytotoxic which would benefit the medical community by providing significant drugs against diabetes. Pragmatic laboratory investigations identified a new precursor to open new doors for new drug discovery.

Effect of Combination of Porang and Moringa Flour on Blood Glucose Levels and Body Weight in Rats

Porang tuber is rich in fiber and low in calories of carbohydrates. Moringa oleifera leaf has a high protein and a low content of lipids. Obesity and diabetes mellitus are the risk factors of cardiovascular disease, also known as cardiovascular disease risk factors. Combining of porang and moringa as feed can increase nutrition without causing weight gain. This study aims to determine these two materials as antidiabetic and antiobesity agents. The samples are porang tuber, a combination of porang tuber and M. oleifera leaves, a combination of M. oleifera leaves and wheat flour, wheat flour, and standard feed of mice. The parameters tested in this study are analysis of macronutrients of feed, loss of weight of mice, average consuming feed in 28 days, and reduction of blood glucose with a glucometer. The results obtained are a combination of porang tuber and moringa had a low contain carbohydrates and a high contain lipids and protein, can reduction in body weight of 21%, the lowest consumption of feed, and the lowest fasting and postprandial blood glucose levels compared to the other feeds. A combination of porang and moringa can be an antidiabetic and antiobesity agent.

A Review of Endophytic Fungi and their Applications in Different Fields of Biotechnology

Endophytic fungus is an intriguing group of organisms that live inside their host's living tissues, which are primarily higher plants. Endophytes generate naturally occurring bioactive chemicals that are thought to operate as an elicitor for the synthesis of secondary metabolites in plants, without causing any disease symptoms in the host cells. By imparting stress tolerance and enhancing host resistance to a range of diseases, this incredibly varied collection of fungus can have a significant influence on plant ecosystems. They are known to improve nutrition through the reversible exchange of nutrients and protect plants from infections, which in turn affects development by releasing plant growth hormones. Endophytic fungus-infected plants exhibit notable increases in biomass, enhance commercial plant output, and are therefore beneficial to the agricultural industry. The potential uses of endophytic fungi as biological vectors, biological control agents, and insecticidal products, sources of secondary metabolites, antimicrobial agents, antitumor compounds, antibiotics, immunosuppressants, and antidiabetic agents make them of biotechnological interest. The current study concentrated on the numerous uses of fungal endophytes in several biotechnology fields.

Pharmaceutical Properties and Phytochemical Profile of Extract Derived from Purple Leaf Graptophyllum pictum (L.) Griff.

Graptophyllum pictum (L.) Griff is a medicinal shrub belonging to the Acanthaceae family and is traditionally used to treat various diseases. Therefore, this study aimed to evaluate the pharmaceutical properties and phytochemical profiles of the methanolic extract of G. pictum. G. pictum leaves was extracted using methanol. Antioxidant, cytotoxic on Michigan Cancer Foundation-7 (MCF-7) and HepG2, antidiabetic, and antibacterial properties were evaluated in vitro. Chemical profile of the extract was identified through qualitative (for phytochemicals), quantitative (for phenolic and flavonoid content), and gas chromatography-mass spectrometry (GC-MS) analysis. The results showed that the extract had potent antioxidant activity against 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) and 2,2-diphenyl-1-picrylhydrazyl radicals with IC50 values of 49.00 ± 3.20 µg/mL and 70.18 ± 3.27 µg/mL, respectively. It also exhibited cytotoxic effects on human breast (MCF-7) and liver (HepG2) carcinoma cells with growth inhibition percentages of 74.29 ± 1.53% and 64.90 ± 1.94%, respectively. The antidiabetic assay showed that the extract had inhibitory effects on α-glucosidase activity with IC50 value 194.59 ± 15.59 µg/mL, indicating its potential to be developed as an antidiabetic agent. Furthermore, it had antibacterial properties against four test strains, and the highest activity was found against Bacillus subtilis American Type Culture Collection 19659, with minimum inhibitory concentration and minimum bactericidal concentration values of 625 µg/mL and 1250 µg/mL, respectively. Phytochemical tests indicated the presence of alkaloids, flavonoid and terpenoids in the extract, with total phenolic content and total flavonoid content of 41.17 ± 2.38 mg gallic acid equivalents/g and 26.52 ± 0.61 mg quercetin equivalent/g, respectively. GC-MS analysis revealed that it contained several active compounds, including eicosane, 2,4-Di-tert-butylphenol, hentriacontane, tetracosane, octacosane, sulfurous acid, 2-methylhexacosane, docosane, heneicosane, 1-propene-1,2,3-tricarboxylic acid, tributyl ester, and pentacosane. The extract derived from G. pictum leaves was a potential source of therapeutic compounds, particularly for antioxidant, antidiabetic, anticancer, and antibacterial agents.

Synthetic Strategies of Thiazolidine-2,4-dione Derivatives for the Development of New Anti-diabetic Agents: Compressive Review.

Thiazolidine-2,4-dione (2,4-TZD) is a flexible pharmacophore and a privileged platform and contains a five-membered ring with a 2-oxygen atom with double bond 2,4- position and one nitrogen atom as well as sulphur containing in the heterocyclic compound. A famous electron-rich nitrogen transporter combines invigorating electronic properties with the prospective for elemental applications. Thiazolidine-2,4-dione analogues have been synthesized using a variety of methods, all of which have shown to have a strong biological effect. The study of the biological activity of Thiazolidine-2,4-dione derivatives has been a fascinating field of pharmaceutical chemistry and has many purposes. This derivative described in the literature between 1995 to 2023 was the focus of this study. Thiazolidine-2,4-diones have been discussed in terms of their introduction, general method, synthetic scheme and antidiabetic significance in the current review. Thiazolidine-2,4-diones are well-known heterocyclic compounds. The synthesis of Thiazolidine-2,4-diones has been described using a variety of methods. Antidiabetic activity has been discovered in several Thiazolidine-2,4-dione derivatives, which enhance further research. The use of Thiazolidine-2,4-diones to treat antidiabetics has piqued researchers' interest in learning more about thiazolidine-2,4-diones.

Alpha-amylase and Alpha-glucosidase Inhibitory Activities of Philippine Indigenous Medicinal Plants

In the Philippines, medicinal plants still provide the first line of therapeutic remedies and their reported efficacy in traditional treatments provides an opportunity for drug discovery and development. The study aimed to evaluate in vitro commonly used Philippine medicinal plants for their alpha-amylase and alpha-glucosidase inhibitory activities as potential sources of antidiabetic agents. The study emphasised the inhibitory activities of 54 medicinal plants against α-amylase and α-glucosidase enzymes. The findings revealed 7 medicinal plants with the highest alpha-glucosidase inhibitory activity of ≥ 50% and 3 with alpha-amylase inhibitory activity of ≥ 20%. Ethyl acetate extract of Cycas sp. exhibited the highest α-glucosidase inhibitory activity with 83.87% ± 1.52 followed by the aqueous extract of cf. Calyptranthera sp. With 82.07% ± 0.14 with Acarbose as the reference standard (99.71% ± 0.63) at 10µg/mL (w/v) concentration. For the alpha-amylase inhibitory assay, the highest bioactivity was observed in ethyl acetate extract of Curcuma longa L. (39.44% ± 1.56) with Acarbose as the reference standard (51.59% ± 0.98) at 10µg/mL (w/v) concentration. These findings suggest the potential of the above-mentioned plants as sources of alpha-amylase and alpha-glucosidase inhibitors that may be used as antidiabetic agents.

Evaluation of Antidiabetic Activity and Cytotoxic Effect of Strontium Nanoparticles Synthesized Using Mimosa Pudica.

Nanotechnology is emerging as a promising approach in the development of novel therapeutic strategies. Nanoparticles, due to their unique physicochemical properties and small size, have the potential to improve the delivery of therapeutic agents, enhance their bioavailability, and increase their efficacy. Among various types of nanoparticles, strontium nanoparticles have gained attention due to their potential antidiabetic activity and cytotoxic effects against cancer cells. Mimosa pudica, also known as "Sensitive Plant" or "Touch-Me-Not," is a medicinal plant known for its diverse pharmacological activities, including antidiabetic and anticancer properties. Recent research has focused on the synthesis of strontium nanoparticles by using Mimosa pudica as a green and sustainable approach. These nanoparticles have shown promising results in terms of their antidiabetic activity and cytotoxic effects against cancer cells. Thus, in this study, the antidiabetic effect was studied using the alpha-amylase inhibitor assay, and the cytotoxic effect was studied using the brine shrimp lethality assay. In these assays, increasing concentration of Mimosa pudica-mediated strontium nanoparticles exhibited increasing antidiabetic and cytotoxic effects, which was similar to the standard used, which is acarbose. Hence, this can be used as a novel antidiabetic and cytotoxic agent in the future.

Myricetin attenuates the inflammatory bowel disease in prediabetic mice via inflammation inhibition and gut microbiota modulation

AbstractMyricetin shows great anti‐inflammatory effect on colitis and supplementation with myricetin could improve gut microbiota dysbiosis. It is reported that the abnormal blood glucose condition of prediabetes could aggravate the progression of inflammation. However, there is no report on whether myricetin has the protective effect on inflammation comorbid prediabetes. This study aimed to explore the effect and potential mechanism of myricetin on dextran sulfate sodium (DSS)‐induced colitis in prediabetic mice. Several indexes related to colitis were evaluated on DSS‐induced prediabetic mice. Myricetin intervention improved body weight loss, disease activity index score in DSS‐induced colitis in prediabetic mice. Myricetin alleviated inflammation by inhibiting proinflammatory cytokines and myeloperoxidase production in DSS‐induced colitis in prediabetic mice. Furthermore, myricetin showed recovery of intestinal barrier integrity by increasing the expression of tight junction proteins (ZO‐1, Occludin and Claudin‐1). At the gut microbiota level, myricetin showed protective effects via modulating gut dysbiosis associated with DSS‐induced colitis in prediabetic mice. In addition, myricetin could significantly increase the short chain fatty acids produced by gut microbiota. Myricetin may be serving as a novel therapeutic agent which could be used in the treatment of DSS‐induced colitis in prediabetic patients in the future with its added value as well reported antidiabetic agent.

Vildagliptin Sustained-release and Dapagliflozin Fixed-dose Combination in the Management of Type 2 Diabetes Mellitus: A Comprehensive Review

Type 2 diabetes mellitus (T2DM) is a complex disease with multiple pathophysiological defects and generally requires a combination of antidiabetic agents to achieve glycemic targets. In this context, a fixed-dose combination (FDC) of dipeptidyl peptidase-4 inhibitors vildagliptin sustained-release (SR) and a sodium-glucose cotransporter type 2 inhibitors dapagliflozin appear to be an attractive approach. There is a strong rationale for combining vildagliptin with dapagliflozin. They have complementary mechanisms of action that address several pathological pathways and are effective at all disease stages. Vildagliptin and dapagliflozin are generally well tolerated, with low hypoglycemia risk. Moreover, they exert beneficial pleiotropic actions on the cardiovascular system and kidneys, lower body weight, and blood pressure and reduce pill burden, providing an important option for managing a broad patient population. For Indian T2DM patients, who have a high prevalence of cardiometabolic risk factors, this combination would be an appropriate choice. Furthermore, the once-daily 100 mg SR dosage of vildagliptin meets the requirements for compliance and adherence. However, data on the vildagliptin SR and dapagliflozin FDC are limited. This review summarizes the available evidence and provides rational, practical guidance for the optimal clinical use of vildagliptin SR and dapagliflozin FDCs in T2DM patients.