Antidiabetic Efficacy Research Articles

A new natural product derived from cyclosorus terminans provides cardiometabolic protection against obese-induced cardiac dysfunction in rats via suppressing mitochondrial dysfunctions and apoptosis

Abstract Background The development of a novel pharmacological target for obesity has long been considered challenging in mitigating the global cardiovascular complications and mortality. Given the cytotoxic effects associated with various anti-obesity drugs, there is growing interest in exploring new natural products as potential sources for bioactive agents to treat obesity-associated diseases with minimal side effects. While Cyclosorus terminans extract has demonstrated anti-diabetic and anti-obese efficacies in adipose-derived stem cells, its cardioprotective effects in high-fat diet (HFD)-induced obese-insulin resistance rat models have never been elucidated. Purpose To examine the effects of long-term Cyclosorus terminans treatment on metabolic, cardiac, and mitochondrial functions and apoptosis in HFD-induced obese-insulin-resistant rat models Methods Male Wistar rats (n=10) were continually fed with HFD and treated with either vehicle (HFV, virgin oil for 2 ml/kg/day, p.o., n=5) or Cyclosorus terminans (HFC, 100 mg/kg/day, p.o., n=5) for 12 weeks. Rats fed a normal diet (NDV, n=5) were used as a control to confirm the development of HFD-induced obesity. The left ventricular ejection fraction (LVEF) and the ratio between early (E) and late atrial (A) ventricular filling velocity were measured using echocardiography, and the homeostatic model assessment for insulin resistance (HOMA-IR) was determined using blood serum. The cardiac tissue was processed to assess mitochondrial reactive oxygen species (ROS) levels, membrane potential (MMP) changes via red/green fluorescence intensity ratio, and apoptotic protein. Results HFV rats became obese and had impaired cardiometabolic function as shown by reducing LVEF, E/A ratio, and increasing HOMA-IR, respectively (Fig. 1A-C). These obese rats also had mitochondrial ROS overproduction, MMP depolarization (reduced red/green ratio), and apoptosis (increased Bax protein expression) (Fig. 1D-F). Treatment with Cyclosorus terminans (HFC) significantly mitigated mitochondrial dysfunction and apoptosis, resulting in cardiometabolic protection in HFD-fed rats (Fig. 1A-F). Conclusion A new natural product derived from Cyclosorus terminans effectively protected the heart against long-term HFD-induced cardiometabolic impairments by reducing mitochondrial dysfunction and apoptosis. These findings demonstrate Cyclosorus terminans as a novel cardiometabolic protection against obesity-related cardiac complications.

Anti-Diabetic Activity of Cordyceps-Fermented Edible Insects by the Promotion of Glucose Absorption.

Insects are considered important food resources for future diet due to diverse nutrients and pharmacological effects. Fermentation is an important strategy of food processing with various beneficial effects such as increasing nutrients, promoting bioavailability, and reducing anti-nutrients. Cordyceps is a mushroom that grows on insects and produces various active ingredients. Therefore, we investigated the effect of Cordyceps-fermentation of insects on the nutritional composition and functional benefits of the insects. Six edible insects: Bombyx mori, Protaetia brevitarsis, Caelifera, Gryllus bimaculatus, Tenebrio molitor, and Allomyrina dichotoma were fermented with Cordyceps militaris to produce mycelia and fruiting bodies. Analysis of nutritional components showed that protein content was increased whereas carbohydrate content was decreased by the fermentation with Cordyceps. In addition, the fermented insects showed anti-diabetic efficacy by the promotion of glucose absorption as evaluated using differentiated L6-GLUT4myc cells. Quantitation using HPLC analysis suggested that cordycepin was produced in both mycelium and fruiting bodies in Cordyceps-fermented edible insects with different amounts depending on insect type and cultivation conditions. Therefore, the fermentation of insects with Cordyceps is expected to increase nutritional values and bioactive constituents and exert anti-diabetic effects.

A Comprehensive Review of Moroccan Medicinal Plants for Diabetes Management.

Moroccan flora, renowned for its diverse medicinal plant species, has long been used in traditional medicine to manage diabetes. This review synthesizes ethnobotanical surveys conducted during the last two decades. Among these plants, 10 prominent Moroccan medicinal plants are evaluated for their phytochemical composition and antidiabetic properties through both in vitro and in vivo studies. The review encompasses a comprehensive analysis of the bioactive compounds identified in these plants, including flavonoids, phenolic acids, terpenoids, and alkaloids. Phytochemical investigations revealed a broad spectrum of secondary metabolites contributing to their therapeutic efficacy. In vitro assays demonstrated the significant inhibition of key enzymes α-amylase and α-glucosidase, while in vivo studies highlighted their potential in reducing blood glucose levels and enhancing insulin secretion. Among the ten plants, notable examples include Trigonella foenum-graecum, Nigella Sativa, and Artemisia herba-alba, each showcasing distinct mechanisms of action, such as enzymatic inhibition and the modulation of glucose metabolism pathways. This review underscores the necessity for further chemical, pharmacological, and clinical research to validate the antidiabetic efficacy of these plants and their active compounds, with a view toward their potential integration into therapeutic practices.

Unraveling the Antidiabetic Effect of Alternantera brasiliana (L.) Kuntze: A Combined in Vitro and in Vivo Approach

Background of the study This study established the antidiabetic efficacy of Alternantera brasiliana in vitro and in vivo, identified the most active fraction and profiled the chemical constituents of the most active fraction. Methodology The leaf of A. brasiliana was air-dried, pulverized and extracted with methanol and evaluated for its α-amylase activity at different concentrations using in vitro method. The in vivo antidiabetic activity of the extract and glibenclamide was evaluated in glucose loaded and streptozotocin-induced diabetic rats using various doses, while the most active partitioned fraction was identified using glucose loaded method followed by identification of its chemical constituents through GC-MS analysis. Results The extract elicited good α-amylase inhibitory potential with IC50 = 0.45 mg/mL. Also, the 50 mg/kg dose demonstrated the highest percentage blood glucose level reduction and significantly ( P > 0.05) comparable to glibenclamide (5 mg/kg) from 0.5 to 4 h. The streptozotocin-induced antidiabetic assay showed that the 50 mg/kg demonstrated better activity than glibenclamide (5 mg/kg) and was significantly comparable on days 10 and 14. The aqueous methanol fraction was the most active fraction with 53% blood glucose level reduction at 4 h. The secondary metabolite profiling identified 30 chemical compounds whereby 1H-Indole-2-carboxylic acid, 6-(4-ethoxyphenyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-, isopropyl ester, Benzo[h]quinoline, 2,4-dimethyl-, thymol and 13,5-trioxane as the major constituents. Conclusion The antidiabetic activity demonstrated by the A. brasiliana extract established its antidiabetic efficacy

In vivo and In silico Insights into the Anti-Diabetic Efficacy of EVOO and Hydroxytyrosol in a Rat Model

Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an eight-week treatment with either EVOO (90 g/kg of the diet) (DO) or hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired β-cell function. In contrast, treatments with EVOO and hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced β-cell survival. Molecular docking and dynamics confirm hydroxytyrosol's high affinity binding to PGC-1α, IRE-1α, and PPAR-γ, particularly IRE-1α, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and hydroxytyrosol. Moreover, the favorable docking scores of hydroxytyrosol with PGC-1α, IRE-1α, and PPAR-γ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.

Locust bean gum glutarate nanocomposite hydrogel microspheres of gliclazide: Optimization by box-Behnken design and preclinical evaluation of anti-diabetic efficacy

In this study, carboxymethyl locust bean gum was synthesized and nanocomposite hydrogel microspheres (GHMs) of gliclazide were produced based on nanosilicate reinforcement and aluminium-ion driven gelation process, followed by covalent crosslinking with glutaric anhydride (GA). The effect of three independent variables (polymer and GA concentration, incubation time) on the drug entrapment efficiency (DEE%) and percent drug release at 8 h, was optimized using Box-Behnken design. The highest DEE (%) and lowest drug release was achieved at the following optimized conditions: polymer (2.43 %), GA (0.34 %), and incubation (27 min). The nanoscilicate-enriched matrix provided a maximum of 75.13 % DEE, 92.33 % gel fraction, and excellent flowability. The optimized microspheres had virtually spherical morphology, according to FE-SEM analysis. FTIR study indicated a hydrogen bonding interaction between the drug and other formulation components. X-ray and DSC measurements suggested that the crystallinity of the drug decreased following integration into the matrix. The optimized GHM demonstrated anomalous diffusion of gliclazide in simulated gastrointestinal fluids for 12 h without disintegration. In streptozotocin (50 mg/kg BW)-induced diabetic rats, the optimized formulation diminished blood glucose level by about 72 % in 12 h. Thus, the nanocomposite GHMs created by combining nanosilicate with GA had an outstanding potential for long-term control of diabetes.

Olive oil and flaxseed oil incorporating niosomes for enhanced in vivo anti-diabetic efficacy of canagliflozin

Background Canagliflozin (CFZ) is broadly implicated for the management of type 2 diabetes mellitus. Unfortunately, it has low oral bioavailability due to poor solubility behavior and restricted membrane permeability. Objective The current work focuses on development of CFZ encapsulated niosomes for enhanced oral anti-diabetic efficacy. Methodology Niosomes comprising Span 60 and cholesterol were formulated both in absence and presence of olive oil or flaxseed oil. These were evaluated in vitro for average vesicular size, structural morphology, CFZ entrapment efficiency, and drug release. Additionally, the oral hypoglycemic effect of CFZ encapsulated niosomes was explored in diabetic rats. Results The fabricated niosomes were negatively charged spherical vesicles with a size range of 103.0–141.7 nm. These entrapped CFZ with efficiency ranging from 92.3% to 96.0%. Drug release investigations reflected that incorporating CFZ into niosomes significantly sustained drug release compared to the aqueous drug dispersion. Oral administration of niosomal formulations significantly enhanced the oral antidiabetic effect of CFZ. Comparing the tested niosomes, similar efficiency was shown eliminating the effect of composition. Conclusion The enhanced oral bioavailability of niosomes’ encapsulated drugs is related to niosomal vesicular structure which allows intact niosomes absorption. The study presented niosomes as promising carriers for improved oral anti-diabetic activity of CFZ.

Enhanced antidiabetic performance through optimized charantin-loaded nanostructured lipid carriers: Formulation and In vivo studies in diabetic mice

The hypoglycemic potential of charantin, a compound from Momordica charantia L., has been well-documented, but its pharmaceutical application faces challenges like poor solubility, low permeability, and suboptimal bioavailability. This study aimed to develop and optimize charantin-loaded nanostructured lipid carriers (Ch-NLCs) to enhance their antidiabetic efficacy. Using a 32 factorial design and high-pressure homogenization, Ch-NLCs were formulated with Precirol and Labrasol as solid and liquid lipids, respectively, combined with surfactants Tween 80 and Poloxamer 188. The optimization focused on key parameters such as particle size, entrapment efficiency (%EE), and zeta potential. FTIR confirmed the interaction between charantin and lipids, while DSC and XRD analyses showed the amorphous nature of Ch-NLCs. The optimized Ch-NLCs exhibited a particle size of 221.0 nm, an %EE of 81.89 %, and a zeta potential of −24.42 mV. In vitro release studies demonstrated a sustained release profile of charantin from the NLCs. In vivo studies on streptozotocin (STZ)-induced diabetic mice revealed significantly enhanced antidiabetic effects of Ch-NLCs compared to pure charantin. Specifically, Ch-NLCs led to substantial reductions in blood glucose levels, total cholesterol (T-Cho), low-density lipoprotein (LDL) and glycosylated hemoglobin (HbA1c) levels, while improving high-density lipoprotein (HDL). These findings highlight the potential of Ch-NLCs as an effective delivery system for charantin in diabetes management. In conclusion, the study successfully engineered and optimized Ch-NLCs, demonstrating their superior pharmacokinetic profiles over pure charantin. These results suggest that Ch-NLCs could be a promising candidate for effective diabetes management, warranting further clinical investigation to confirm their therapeutic potential in human subjects.

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.

Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds

In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both in vitro and in vivo assays. The tested compounds 7a-7j demonstrated In vitro inhibitory potential against α-glucosidase, as indicated by their IC50 values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC50 value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for in vivo evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both in vitro and in vivo, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the α-glucosidase enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.

Ameliorative Effects of Essential Oils on Diabetes Mellitus: A Review.

Diabetes mellitus (DM) is a metabolic disorder and is responsible for the death of more than 4.2 million people in 2019. Synthetic drugs for DM like metformin have been reported to induce numerous complications and side effects. Reports suggested that essential plant oil has been used as an herbal remedy to lower blood glucose levels. Essential oils (EOs) are complex combinations of small molecules obtained from plants via the process of steam distillation and several solvents. EOs have already shown great efficacy as antimicrobials, anti-inflammatory, hepatoprotective, and anti-hypertensive. This review aims to summarize some potential EOs that have been reported to have anti-diabetic activity both in preclinical and clinical aspects while summarizing the probable mechanism of action. The authors went through a vast number of articles from various scientific databases like Google Scholar, PubMed, and Web of Science. It was found that EO from a total of 20 plants has been pre-clinically investigated to have anti-diabetic potential. Besides this, clinical studies have reported the antidiabetic efficacy of EOs from Nigella sativa and Cuminum cyminum at different concentrations. Bioactive phytoconstituents like carvacrol, thymol, α- pinene, via . obtained from EOs ameliorate DM by inhibiting α-GLUC, α-amylase, lipase enzymes and increasing GLUT-4 expression, AKT phosphorylation, via . Although fewer in number, EOs from plant sources have demonstrated significant efficacy in DM. Proper elucidation of the anti-diabetic efficacy of the EOs may open up new avenues for drug discovery and development subjected to clinical studies.

Exploring the Biological Effects of Anti-Diabetic Vanadium Compounds in the Liver, Heart and Brain.

The prevalence of diabetes mellitus and diabetes-related complications is rapidly increasing worldwide, placing a substantial financial burden on healthcare systems. Approximately 537 million adults are currently diagnosed with type 1 or type 2 diabetes globally. However, interestingly, the increasing morbidity rate is primarily influenced by the effects of long-term hyperglycemia on vital organs such as the brain, the liver and the heart rather than the ability of the body to use glucose effectively. This can be attributed to the summation of the detrimental effects of excessive glucose on major vascular systems and the harmful side effects attributed to the current treatment associated with managing the disease. These drugs have been implicated in the onset and progression of cardiovascular disease, hepatocyte injury and cognitive dysfunction, thereby warranting extensive research into alternative treatment strategies. Literature has shown significant progress in utilizing metal-based compounds, specifically those containing transition metals such as zinc, magnesium and vanadium, in managing hyperglycaemia. Amongst these metals, research carried out on vanadium reflected the most promising anti-diabetic efficacy in cell culture and animal studies. This was attributed to the ability to improve glucose management in the bloodstream by enhancing its uptake and metabolism in the kidney, brain, skeletal muscle, heart and liver. Despite this, organic vanadium was considered toxic due to its accumulative characteristics. To alleviate vanadium's toxic nature while subsequently manipulating its therapeutic properties, vanadium complexes were synthesized using either vanadate or vanadyl as a base compound. This review attempts to evaluate organic vanadium salts' therapeutic and toxic effects, highlight vanadium complexes' research and provide insight into the novel dioxidovanadium complex synthesized in our laboratory to alleviate hyperglycaemia-associated macrovascular complications in the brain, heart and liver.

Mycosynthesis and Characterization of Zinc Oxide Nanoparticles from Shiitake Mushrooms (Lentinula edodes): Potential Antidiabetic, Antimicrobial and Antioxidant Efficacy

Mycosynthesis and Characterization of Zinc Oxide Nanoparticles from Shiitake Mushrooms (Lentinula edodes): Potential Antidiabetic, Antimicrobial and Antioxidant Efficacy

The Role and Mechanism of Probiotics Supplementation in Blood Glucose Regulation: A Review.

With economic growth and improved living standards, the incidence of metabolic diseases such as diabetes mellitus caused by over-nutrition has risen sharply worldwide. Elevated blood glucose and complications in patients seriously affect the quality of life and increase the economic burden. There are limitations and side effects of current hypoglycemic drugs, while probiotics, which are safe, economical, and effective, have good application prospects in disease prevention and remodeling of intestinal microecological health and are gradually becoming a research hotspot for diabetes prevention and treatment, capable of lowering blood glucose and alleviating complications, among other things. Probiotic supplementation is a microbiologically based approach to the treatment of type 2 diabetes mellitus (T2DM), which can achieve anti-diabetic efficacy through the regulation of different tissues and metabolic pathways. In this study, we summarize recent findings that probiotic intake can achieve blood glucose regulation by modulating intestinal flora, decreasing chronic low-grade inflammation, modulating glucagon-like peptide-1 (GLP-1), decreasing oxidative stress, ameliorating insulin resistance, and increasing short-chain fatty acids (SCFAs) content. Moreover, the mechanism, application, development prospect, and challenges of probiotics regulating blood glucose were discussed to provide theoretical references and a guiding basis for the development of probiotic preparations and related functional foods regulating blood glucose.

Biobased Polybutyrolactam Nanofiber with Excellent Biodegradability and Cell Growth for Sustainable Healthcare Textiles.

The white pollution caused by unsustainable materials is a significant challenge around the globe. Here, a novel and fully biobased polybutyrolactam (PBY) nanofiber membrane was fabricated via the electrospinning method. As-spun PBY nanofiber membranes have good thermal stability, high porosity of up to 71.94%, and excellent wetting behavior. The biodegradability in soil, UV aging irradiation, and seawater was investigated. The PBY nanofiber membrane is almost completely degraded in the soil within 80 days, showing excellent degradability. More interestingly, γ-aminobutyric acid, as a healthcare agent with intrinsic hypotensive, tranquilizing, diuretic, and antidiabetic efficacy, can be detected in the degradation intermediates. In addition, the PBY nanofiber membrane also exhibits antibacterial ability against Escherichia coli. As a fully biomass-derived material, the PBY membrane has excellent biodegradable performance in various environments as well as negligible cytotoxicity and commendable cell proliferation. Our PBY nanofiber membrane shows great potential as biodegradable packaging and in vitro healthcare materials.

Assessing anti oxidant, antidiabetic potential and GCMS profiling of ethanolic root bark extract of Zanthoxylum rhetsa (Roxb.) DC: Supported by in vitro, in vivo and in silico molecular modeling.

Zanthoxylum rhetsa (ZR) is used traditionally to manage a variety of ailments, including diabetes. Oxidative stress may accelerate the diabetic condition. The available antidiabetic and antioxidant drugs have many shortcomings including resistance, inefficiency, higher dose, side effects and costs. The goal of the current investigation was to assess the antioxidant capacity and antidiabetic activity of an ethanolic extract of Zanthoxylum rhetsa root bark (ZRRB) through in vitro, in vivo, and in silico methods. The antioxidant capacity of the ZRRB extract was measured using both the DPPH radical assay and the total antioxidant activity test. The oral glucose tolerance test (OGTT) and alloxan-induced diabetic mice model were also used to examine in vivo antidiabetic efficacy. Phytochemicals identification was done by GCMS analysis. Additionally, computational methods such as molecular docking, ADMET analysis, and molecular dynamics (MD) modeling were performed to determine the above pharmacological effects. The extract demonstrated significant DPPH scavenging activity (IC50 = 42.65 μg/mL). In the OGTT test and alloxan-induced diabetes mice model, the extract effectively lowered blood glucose levels. Furthermore, in vitro inhibition of pancreatic α-amylase studies demonstrated the ZRRB extract as a good antidiabetic crude drug (IC50 = 81.45 μg/mL). GCMS investigation confirmed that the crude extract contains 16 major phytoconstituents, which were docked with human peroxiredoxin-5, α-amylase, and sulfonylurea receptor 1. Docking and pharmacokinetic studies demonstrated that among 16 phytoconstituents, 6H-indolo[3,2,1-de] [1,5]naphthyridin-6-one (CID: 97176) showed the highest binding affinity to targeted enzymes, and imitated Lipinski's rule of five. Furthermore, MD simulation data confirmed that the aforementioned compound is very steady to the binding site of α-amylase and sulfonylurea receptor 1 receptors. Findings from in vitro, in vivo and in silico investigation suggest that ZRRB extract contains a lead compound that could be a potent source of antidiabetic drug candidate.

Acute Pre- and Post-administration of Lactiplantibacillus plantarum 2034 and Its Secretory Metabolites Ameliorates Hyperglycaemia, Hyperlipidaemia, and Oxidative Stress in Diabetic Rats.

The global prevalence rate of diabetes in 2021 was 6.1% making diabetes one of the top 10 causes of death. Prolonged use of antidiabetic medications is associated with various side effects; therefore, alternative treatment strategies for diabetes need exploration. The antidiabetic properties of Lactiplantibacillus plantarum 2034 was explored both in in vitro and in vivo studies. Secretory metabolites of probiotic L. plantarum 2034 exhibited alpha-glucosidase, alpha-amylase, and lipase inhibitory activities, in vitro. Further, the antidiabetic efficacy of 2034 was evaluated in streptozotocin-nicotinamide-induced diabetic rats. In the therapeutic model, oral administration of L. plantarum resulted in normalization of body weight, fasting blood glucose, total cholesterol (TC), and liver enzymes, and significant (p < 0.05) reduction in insulin and triglyceride (TG) levels. Histological evaluation of pancreas, liver, and kidney showed restoration of normal architecture in probiotic-treated group. Similarly, in a preventive + therapeutic model, 14days of pre-administration of 2034 in pre, pre + post, and cell-free supernatant resulted in significant reduction in glucose, TG, TC, and liver biochemistry of diabetic rats as compared to untreated diabetic rats. An oral glucose tolerance test showed that the glucose levels normalized within 90min in all the treated groups. Further, the oxidative stress parameters were also studied that showed that in all the treated groups, the concentration of antioxidant enzymes significantly (p < 0.05) increased as compared to diabetic untreated rats. Thus, administration of L. plantarum 2034 and its metabolites successfully ameliorated hyperglycaemia and hypercholesterolemia in both the models probably due to inhibition of gut enzymes and by increasing the concentration of liver antioxidant enzymes.

Evaluation of anti-diabetic, anti-oxidant and anti-bacterial activities of essential oil collected from wildly growing Calotropis gigantea (Linn.) Aiton f. and its therapeutic applications: insights from chemical profiling, in-vitro and in-silico studies

Calotropis gigantea, often known as giant milkweed, the plant is widely known for producing herbal essential oils that are used as traditional and complementary medicine to cure various ailments. The aim of the present study was evaluation of anti-diabetic, anti-oxidant and anti-bacterial activities of essential oil collected from wildly growing Calotropis gigantea and its its therapeutic applications via chemical profiling, in-vitro and in-silico studies. After Calotropis gigantea (CEO) essential oil was extracted by hydro-distillation, its phytochemical, antioxidant, antibacterial, and anti-diabetic properties were assessed. Fingerprint analysis and GC-FID were used to create a chemical profile. Various tests for antioxidants, such as DPPH, nitric oxide radical, and iron chelating activity, were conducted. The disk diffusion approach was used for antibacterial efficacy against Gram-negative (G-) bacteria. The test of α-amylase inhibition was utilized to investigate anti-diabetic efficacy. In-silico analysis was also conducted to find out interaction of some components to α-amylase enzyme. Chemical profiling indicated the presence of phytol (24%), stearic acid (10%), and cyclohexyl ketone (6%), as predominant components. There was notable antioxidant activity ranged from 82 to 97% for various assays. IC50 values for various assays were iron chelating activity: 18.610, DPPH scavenging activity: 28.246, nitric oxide radical scavenging activity: 58.113. CEO showed a zone of inhibition value of 0.5 cm and significant antibacterial activity against Gram-negative (G-) bacteria. CEO blocked α-amylase in dose-dependent way. At a higher amount of 250 µl, CEO inhibition was 63% and mode of inhibition un-competitive. In-silico analysis validated the blocking of α-amylase and interaction of phytocomponents to α-amylase enzyme which were further validated by UV and fluorescent quenching techniques. It was determined that CEO may be extensively used in many different industries, including as food, herbal medicine, cosmetics.

Structurally Diverse Stilbenoids as Potent α-Glucosidase Inhibitors with Antidiabetic Effect from Morus alba.

Fifteen stilbenoid derivatives, including five previously undescribed ones (albaphenols A-E, 1-5) with diverse scaffolds, were obtained from the well-known agricultural economic tree Morus alba. Their structures, including absolute stereochemistries, were fully characterized by detailed interpretation of spectroscopic data and quantum chemical computational analyses of nuclear magnetic resonance (NMR) and electric circular dichroism (ECD). Albaphenol A (1) features an unprecedented rearranged carbon skeleton incorporating a novel 2-oxaspiro[bicyclo[3.2.1]octane-6,3'-furan] motif; albaphenol C (3) is likely derived from a cometabolite through an interesting intramolecular transesterification reaction; and albaphenol E (5) bears a cleavage-reconnection scaffold via a dioxane ring. All of the compounds exhibited significant inhibition against the diabetic target α-glucosidase, with low to submicromole IC50 values (0.70-8.27 μM), and the binding modes of selected molecules with the enzyme were further investigated by fluorescence quenching, kinetics, and molecular docking experiments. The antidiabetic effect of the most active and abundant mulberrofuran G (6) was further assessed in vivo in diabetic mice, revealing potent antihyperglycemic activity and comparable antidiabetic efficacy to the clinical drug acarbose.

Poly(allylamine)-adorned heptylcarboxymethyl galactomannan nanocarriers of canagliflozin for controlling type-2 diabetes: Optimization by Box-Behnken design and in vivo performance

In the past three decades, the prevalence of type-2 diabetes has arisen dramatically in countries of all income levels. A novel, most effective nanotechnology-based strategy may reduce the prevalence of diabetes. Recently, the shell-crosslinked polysaccharide-based micellar nanocarriers (MNCs) have shown great promise in terms of stability, controlled drug release, and improved in vivo performance. In this study, heptyl carboxymethyl guar gum was synthesized and characterized by ATR-FTIR, 1HNMR spectroscopy, surface charge, critical micelle concentration (23.9 μg/mL), and cytotoxicity analysis. Box-Behnken design was used to optimize the diameter, zeta potential, drug entrapment efficiency (DEE), and drug release characteristics of poly (allylamine)-crosslinked MNCs containing canagliflozin. The optimized MNCs revealed spherical morphology under TEM and had 149.3 nm diameter (PDI 21.2 %), +53.8 mV zeta potential, and 84 % DEE. The MNCs released about 63 % of the drug in 12 h under varying pH of the simulated gastrointestinal fluid. DSC and x-ray analyses suggested amorphous dispersion of drugs in the MNCs. CAM assay demonstrated the biocompatibility of the MNCs. The MNCs showed hemolysis of <1 %, 85 % mucin adsorption, and stability over three months. The MNCs demonstrated excellent anti-diabetic efficacy in streptozotocin-nicotinamide-induced diabetic rats, continuously lowering blood glucose levels up to 12 h.