Molecular Modeling, Synthesis, and Antihyperglycemic Activity of the New Benzimidazole Derivatives - Imidazoline Receptor Agonists.

Introduction: The paper presents the results of a study on the first synthesized benzimidazole derivatives obtained from labile nature carboxylic acids. The synthesis conditions of these substances were studied, their structure was proved, and some components were found to have sugar-reducing activity on the model of alloxan diabetes in rats. Methods: The study used molecular modeling methods such as docking based on the evolutionary model (igemdock), RP_HPLC method to monitor the synthesis reaction, and 1H NMR and 13C NMR, and other methods of organic chemistry to confirm the structures of synthesized substances. Results & Discussion: The docking showed that the ursodeoxycholic acid benzimidazole derivatives have high tropics to all imidazoline receptor carriers (PDB ID: 2XCG, 2bk3, 3p0c, 1QH4). The ursodeoxycholic acid benzimidazole derivative and arginine and histidine benzimidazole derivatives showed the highest sugar-lowering activity in the experiment on alloxan-diabetic rats. For these derivatives, the difference in glucose levels of treated rats was significant against untreated control. Therefore, the new derivatives of benzimidazole and labile natural organic acids can be used to create new classes of imidazoline receptor inhibitors for the treatment of diabetes mellitus and hypertension.

Valorisation of olive pomace: phenolic prospecting and biological potential.

Phenolic compounds were extracted from biphasic olive pomace and their biological potential was characterised. Two different extracts were prepared, E1 (40% methanol) and E2 (80% methanol), both subjected to agitation (180 min) and 70 °C. LC-ESI-qTOF-MS was used for individual quantification of the extracted phenolic compounds. The antioxidant activity was determined using different methods, including nitric oxide, DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radical. The enzymes α-amylase and α-glucosidase were used to evaluate the antihyperglycemic potential and sulforhodamine B and MTT (tetrazolium salt) for antitumor activity. To evaluate the antimicrobial activity, minimum inhibitory concentration and minimum bactericidal concentration of the extracts, the disc diffusion technique was used. Among the phenolic compounds present, tyrosol was highlighted in both extracts, as well as the anti-hyperglycemic effects, antitumor action and antioxidant activity. The antimicrobial activity found in the extracts was considered moderate to weak.

Association between Glucagon-like Peptide-1 Receptor Agonists and the Risk of Glaucoma in Individuals with Type 2 Diabetes.

PURPOSE: To examine the association between Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) use and the development of glaucoma in individuals with type 2 diabetes. DESIGN: Nationwide, nested case-control study. PARTICIPANTS: From a nationwide cohort of 264708 individuals, we identified 1,737 incident glaucoma cases and matched them to 8685 glaucoma-free controls, all aged above 21 years old and treated with metformin and a second-line antihyperglycemic drug formulation, with no history of glaucoma, eye trauma or eye surgery. METHODS: Cases were incidence density matched to five controls by birth year, sex, and date of second-line treatment initiation. MAIN OUTCOME MEASURES: Conditional logistic regression was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for glaucoma, defined by first-time diagnosis, first-time use of glaucoma-specific medication, or first-time glaucoma-specific surgical intervention. RESULTS: Compared with the reference group, who received treatments other than GLP-1RA, individuals who were exposed to GLP-1RA treatment exhibited a lower risk of incident glaucoma (HR: 0.81, CI: 0.70 - 0.94, p = 0.006). Prolonged treatment extending beyond three years lowered the risk even further (HR: 0.71, CI: 0.55 - 0.91, p = 0.007). Treatment with GLP-1RA for 0 - 1 years (HR: 0.89, CI: 0.70 - 1.14, p = 0.35) and 1 - 3 years (HR: 0.85, CI: 0.67 - 1.06, p = 0.15) were not significant. CONCLUSIONS: GLP-1RA exposure was associated with a lower risk of developing glaucoma compared to receiving other second-line antihyperglycemic medication.

Effect of Drugs Used in Pharmacotherapy of Type 2 Diabetes on Bone Density and Risk of Bone Fractures.

This review summarizes the complex relationship between medications used to treat type 2 diabetes and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density; thus, we analyzed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, and GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control, and potential medication-related effects on bone.

Interactions between Gut Microbiota and Oral Antihyperglycemic Drugs: A Systematic Review.

The intestinal microbiota refers to the collection of microorganisms that exist in the human gut. It has been said that bacteria influence the development of metabolic diseases, such as diabetes mellitus, as they have roles in immunomodulation, protection against pathogens, blood vessel growth, repairing the intestinal wall, and the development of the neurological system. In this review, we look at the latest research regarding interactions between gut microbiota and oral antihyperglycemic drugs and we present data suggesting that the microbiome may help counteract the reduced glucose tolerance and insulin resistance associated with metabolic disorders. We found that antidiabetic drugs can have significant impacts on gut microbiota composition and function, potentially influencing both the efficacy and side effects of these medications. Additionally, we discovered that microbial-based therapeutics, including probiotics, prebiotics, and postbiotics, and fecal microbiota can be considered when discussing preventive measures and personalized treatment options for type 2 diabetes mellitus. Understanding how antidiabetic drugs modulate gut microbiota composition and function is essential for optimizing their therapeutic efficacy and minimizing potential adverse effects. The relationship between the gut microbiota and glycemic agents, not fully understood, is currently the subject of increasing research and discussion. It has been proven that the microbiome can impact the effectiveness of the medications, but further research in this field may uncover novel therapeutic strategies for diabetes and other metabolic disorders by targeting the gut microbiota.

Antihyperglycemic effects of triterpenoid saponins from the seeds of Aesculus chinensis Bge.

Six undescribed triterpenoid saponins, namely aescuchinosides A-F, along with seven known triterpenoid saponins, were isolated from the seeds of Aesculus chinensis. Barrigenol-like triterpenoids (BATs) constitute these saponins. Protoaescigenin serves as their aglycone, with various oxygen-containing groups, including acetyl, isobutyryl, tigloyl, and angeloyl groups situated at C-21, C-22, and C-28. Various techniques, including 1D and 2D-NMR spectroscopy, high-resolution mass spectrometry, and acid hydrolysis, were employed to determine the structures of these compounds. The antihyperglycemic effects of the isolated compounds were examined in insulin -resistant HepG2 cells induced by palmitic acid treatment. At a concentration of 6 µM, aesculinoside F exhibited a significant increase in glucose consumption. In addition, aesculinoside F demonstrated the potential to improve insulin resistant by upregulating the PI3K/AKT pathway. These results indicate that the seeds of A.chinensis hold promising potential for preventing insulin resistant related disease.

A comparison study on polysaccharides extracted from banana flower using different methods: Physicochemical characterization, and antioxidant and antihyperglycemic activities.

This work investigated and compared the physicochemical characteristics, and antioxidant and antihyperglycemic properties in vitro of polysaccharides from a single banana flower variety (BFPs) extracted by different methods. BFPs extracted using hot water (HWE), acidic (CAE), alkaline (AAE), enzymatic (EAE), ultrasonic (UAE) and hot water-alkaline (HAE) methods showed different chemical composition, monosaccharide composition, molecular weight, chain conformation and surface morphology, but similar infrared spectra characteristic, main glycosidic residues, crystalline internal and thermal stability, suggesting that six methods have diverse impacts on the degradation of BFPs without changing the main structure. Then, among six BFPs, the stronger antioxidant activity in vitro was found in BFP extracted by HAE, which was attributed to its maximum uronic acid content (21.67 %) and phenolic content (0.73 %), and moderate molecular weight (158.48 kDa). The highest arabinose and guluronic acid contents (18.59 % and 1.31 % in molar ratios, respectively) and the lowest uronic acid content (14.30 %) in BFP extracted by HWE contributed to its better α-glucosidase inhibitory activity in vitro (66.55 %). The data offered theoretical evidence for choosing suitable extraction methods to acquire BFPs with targeted biological activities for applications, in which HAE and HWE could serve as beneficial methods for preparing antioxidant BFP and antihyperglycemic BFP, respectively.

In vitro and In vivo Determination of Biological Activities of Bitter Gourd (Momordica charantia L.) Peel, Flesh and Seeds.

Momordica charantia L. has been remained a well-known medicinal vegetable used traditionally. However, which part is most effective against which disorder, has been remained undiscovered yet. The objective of this study was to examine the antimicrobial, antihyperlipidemic and antihyperglycemic activities of peel, flesh, and seeds of bitter gourd, through in vitro and in vivo assays. Ethanolic extracts from powders of three fractions of bitter gourd were assessed for antimicrobial potential against bacterial and fungal strains, whereas, powders of these fractions were used to determine antihyperlipidemic and antihyperglycemic activity, in alloxan induced diabetic rats. Our results showed that BSE exhibited better antimicrobial activity against Bacillus cereus, whereas BFE exhibited better against Escherichia coli. Blood glucose was significantly lowered by all three powders in a dose dependent manner, when fed to diabetic rats, with the highest decrease by BSP, which reduced the glucose level from 296.20 ± 2.00 mg/dl to 123.10 ± 0.80 mg/dl, at 15 mg dose, after 28 days trial. Elevated levels of TC (101.18 ± 0.65 mg/dl), TG (83.69 ± 0.61 mg/dl) and LDL-C (25.90 ± 0.09 mg/dl) in positive control rats were lowered down in well manners by BSP at 15 mg dose, to 86.30 ± 0.53, 67.70 ± 0.53 and 19.32 ± 0.06 mg/dl, respectively. As compared to BFP and BPP, BSP showed significant involvement in antibacterial, antihyperglycemic, and antihyperlipidemic actions. Along with the edible flesh, peels and seeds, which are usually discarded as waste, could also be utilized for development of pharma foods capable of promoting health.

Hypoglycemic activities of flowers of Xanthoceras sorbifolia and identification of anti-oxidant components by off-line UPLC-QTOF-MS/MS-free radical scavenging detection.

Objective: To identify phytochemical constituents present in the extract of flowers of Xanthoceras sorbifolia and evaluate their anti-oxidant and anti-hyperglycemic capacities. Methods: The AlCl3 colorimetric method and Prussian Blue assay were used to determine the contents of total flavonoids and total phenolic acids in extraction layers, and the bioactive layers was screened through anti - oxidative activity in vitro. The Waters ACQUITY UPLC system and a Waters ACQUITY UPLC BEH C18 column (2.0 mm × 150 mm, 5 µm) were used to identify the ingredients. And anti-oxidative ingredients were screened by off-line UPLC-QTOF-MS/MS-free radical scavenging. The ameliorative role of it was further evaluated in a high-fat, streptozotocin-induced type 2 diabetic rat model and the study was carried out on NADPH oxidase (PDB ID: 2CDU) by molecular docking. Results: Combined with the results of activity screening in vitro, the anti - oxidative part was identified as the ethyl acetate layer. A total of 24 chemical constituents were identified by liquid chromatography-mass spectrometry in the ethyl acetate layer and 13 main anti-oxidative active constituents were preliminarily screened out through off-line UPLC-QTOF-MS/MS-free radical scavenging. In vivo experiments showed that flowers of X. sorbifolia could significantly reduce the blood glucose level of diabetic mice and alleviate liver cell damage. Based on the results of docking analysis related to the identified phytocompounds and oxidase which involved in type 2 diabetes, quercetin 3-O-rutinoside, kaempferol-3-O-rhamnoside, isorhamnetin-3-O-glucoside, and isoquercitrin showed a better inhibitory profile. Conclusion: The ethyl acetate layer was rich in flavonoids and phenolic acids and had significant anti-oxidant activity, which could prevent hyperglycemia. This observed activity profile suggested X. sorbifolia flowers as a promising new source of tea to develop alternative natural anti-diabetic products with a high safety margin.

Analyzing the Antihyperglycemic Effect of Cissus quadrangularis and Bacopa monnieri on 3T3-L1 Cell Lines.

Background Cissus quadrangularis is a perennial shrub of the grape family. Other names for it include devil's backbone, veld grape, and pirandai (Tamil). Bacopa monnieri, a perennial plant, is native to wetlands in eastern and southern India. The 3T3-L1 cell line, which was created from 3T3 cells, was used in the scientific study. The current study's purpose is to evaluate the antihyperglycemic benefits of B. monnieri and C. quadrangularis, which will be added to the current arsenal of efficient herbal hypoglycemic medications. Aim To analyze and compare the anti-hyperglycaemic effects of the two plant extracts, C. quadrangularis and B. monnieri using a 3T3-L1 cell line. Materials and methods C. quadrangularis seeds were gathered, and extraction was conducted. The B. monnieri plant was harvested, and a rotary evaporator was used to extract the flower. Adipocyte cells were obtained from NCCS, Pune. A CO2 incubator was used to incubate the cells. The MTT assay and gene expression analysis were done on the cell line samples. Results The antihyperglycemic effects of C. quadrangularis IRS mRNA levels of 0.7 and AKT mRNA levels of 0.7 are compared to B. monnieri IRS1 mRNA levels of 0.6 and AKT mRNA levels of 0.6 to build better diabetic treatments. The antihyperglycemic benefits of C. quadrangularis levels of IRS mRNA and AKT mRNA are compared to the influence of B. monnieri IRS1 mRNA and AKT mRNA on the development of better diabetic drugs. Conclusion Comparing the effects of C. quadrangularis and B. monnieri on the 3T3 cell line by gene expression of IRS mRNA and AKT mRNA suggests that the particular AKT downregulation shows that insulin suppresses gluconeogenesis and C. quadrangularis inhibits hyperglycemia in 3T3-L1 cells, while research on in vitro rats suggests that B. monnieri may minimize the signs and symptoms of diabetes via enhancing IRS1/AKT signaling.

Phytochemical analysis and antihyperglycemic activity of Castilleja arvensis.

Castilleja genus comprises approximately 211 species, some of them exhibiting potential in treating various diseases. Remarkably, despite its abundance, there is a significant lack of scientific studies that explore the chemical composition and/or therapeutic activity of this genus. In this work, the chemical composition of Castilleja arvensis was determined, and its antihyperglycemic activity was evaluated in vivo, in vitro, and ex vivo. Hydroalcoholic extract of C. arvensis (HECa) was obtained from the maceration of aerial parts. HECa was fractionated by liquid-liquid extractions to obtain the CH2Cl2 fraction (DF), EtOAc fraction (EF), n-BuOH fraction (BF) and aqueous residue (AR). The antihyperglycemic activity was determined in vivo through oral glucose and sucrose tolerance tests in normoglycemic CD-1 mice. Ex vivo assays were performed to determine intestinal glucose absorption, muscular glucose uptake and hepatic glucose production. α-glucosidase inhibitory activity was evaluated in vitro. Phytochemical screening was carried out through conventional chromatography techniques. Structure elucidation of the isolated compounds was performed by GC-MS and NMR experiments. HECa, its fractions and AR showed significant antihyperglycemic activity in vivo. According to the in vitro and ex vivo assays, this effect can be attributed to different mechanisms of action, including a delay in intestinal glucose absorption, an improvement in insulin sensitivity, and the regulation of hepatic glucose production. These effects may be due to different metabolites identified in fractions from the HECa, including genkwanin, acacetin, verbascoside and ipolamiide. Thus, current research shows that C. arvensis is an important source of bioactive compounds for the management of glycemia.

Genetic prediction of antihyperglycemic drug targets and risk of epilepsy: a mendelian randomisation study.

A connection between diabetes and an increased risk of epilepsy has been suggested by observational studies. Animal studies have also shown that antihyperglycemic drugs can improve seizures. However, it is unclear whether antihyperglycemic drugs have a causal role in epilepsy in humans. To investigate this potential causal relationship, a Mendelian randomisation study was conducted using International League Against Epilepsy data as the discovery set and FinnGen data as the replication set. It was discovered that three antidiabetic drug target genes, ETFDH, CYP21A2 and CYP2D6, were involved in the occurrence of epilepsy. In particular, ETFDH was identified as a target gene in both the discovery set (inverse variance weighting [IVW], odds ratio [OR] = 1.018, 95% confidence interval [CI], 1.004-1.033, p = 0.009) and replication set (IVW, OR = 1.074, 95% CI, 1.034-1.114, p = 0.00016), and CYP21A2 was identified in the discovery set (IVW, OR = 1.029, 95% CI, 1.005-1.053, p = 0.016) and replication set (IVW, OR = 1.057, 95% CI, 1.001-1.116, p = 0.045) as having a causal association with an increased risk of epilepsy. Conversely, the CYP2D6 gene was found to be a protective factor for epilepsy in both the discovery set (IVW, OR = 0.0984, 95% CI, 0.969-0.998, p = 0.025) and replication set (IVW, OR = 0.977, 95% CI, 0.955-1.000, p = 0.046). A search of DrugBank revealed that metformin, an anti-glucose drug, is an inhibitor of the ETFDH gene and may have a potential therapeutic effect on epilepsy.

Characterization and bioaccessibility assessment of bioactive compounds from camu-camu (Myrciaria dubia) powders and their food applications.

Camu-camu (Myrciaria dubia) is a tropical fruit known for its content of bioactive compounds. This study aimed to evaluate physicochemically, morphologically, andsensorialpowders from camu-camu obtained by spray-drying at two inlet temperatures (150 °C and 180 °C) with three encapsulating agents (maltodextrin, whey protein and a 50:50 mixture of both) and by freeze-drying of whole fruit. The use of maltodextrin protected bet anthocyanins (cyanidin-3-glucoside (C3G) and delphinidin-3-glucoside (D3G)), but whey protein showed a better protective effect on ascorbic and malic acids. These facts were confirmed during the storage stability test, finding that relative humidity is a critical variable in preserving the bioactive compounds of camu-camu powders. The powders with the highest content of bioactive compounds were added to a yogurt and a white grape juice, and then sensory evaluated. The bioaccessibility studies in gastric and intestinal phases showed better recovery percentages of bioactive compounds in camu-camu powders (up to 60.8 %) and beverages (up to 90 %) for C3G, D3G, ascorbic acid, and malic acid than in the fruit juice. Dehydration of camu-camu (M. dubia) is a strategy to increase the bioactive compounds stability, modulate the fruit sensory properties, and improve their bioavailability after incorporation in food matrices.

An Insight into the Combat Strategies for the Treatment of Type 2 Diabetes Mellitus.

Diabetes is a chronic, and metabolic disorder that has gained epidemic proportions in the past few decades creating a threat throughout the globe. It is characterized by increased glucose levels that may be due to immune-mediated disorders (T1DM), insulin resistance or inability to produce sufficient insulin by ß-pancreatic cells (T2DM), gestational, or an increasingly sedentary lifestyle. The progression of the disease is marked by several pathological changes in the body like nephropathy, retinopathy, and various cardiovascular complications. Treatment options for T1DM are majorly focused on insulin replacement therapy. While T2DM is generally treated through oral hypoglycemics that include metformin, sulfonylureas, thiazolidinediones, meglitinides, incretins, SGLT-2 inhibitors, and amylin antagonists. Multidrug therapy is often recommended when patients are found incompliant with the first-line therapy. Despite the considerable therapeutic benefits of these oral hypoglycemics, there lie greater side effects (weight variation, upset stomach, skin rashes, and risk of hepatic disease), and limitations including short half-life, frequent dosing, and differential bioavailability which inspires the researchers to pursue novel drug targets and small molecules having promising clinical efficacy posing minimum side-effects. This review summarizes some of the current emerging novel approaches along with the conventional drug targets to treat type 2 diabetes.

Zinc-Phthalocyanine Loaded PLGA-PVA-Chitosan Nanosystem for the Enhancement of Antidiabetic Activity.

Zinc, one of the most common nutraceutical agents, proved to be effective for diabetes as it regulates the blood glucose level by inhibiting glucagon secretion. However, the hepatotoxicity of zinc creates necrosis, hepatic glycogen depletion, and apoptosis of hepatocytes at the concentration of 10 µg/kg. Phthalocyanine, a blue-colored compound, is an aromatic macrocyclic compound with good antioxidant ability owing to its heterocyclic nitrogen conjugation. The conjugation of zinc with phthalocyanine aimed to reduce the toxicity associated with zinc and enhance the antidiabetic activity at a lower dose. Hence, the present research work possessed the insights of the synthetic aspect of zinc with phthalocyanine along with its entrapment in the poly(lactic-co-glycolic acid) (PLGA)-chitosan nanosystem via oral administration in the treatment of diabetes. A nanoprecipitation technique was implemented for the synthesis of PLGA chitosan nanoparticles, and formulation was further optimized using a central composite design. Twenty trials provided by the software selected optimum concentrations of PLGA, poly(vinyl alcohol) (PVA), and chitosan in consideration with particle size up to 335.6 nm, zeta potential 27.87 mV, and entrapment efficiency of 75.67 ± 8.13%. Addition of chitosan to the nanocarrier system for controlling the release of the drug for 3 days was accompanied by the improvement in the glucose level within 28 days. The delivery of the nanoparticles showed enhancement in the cholesterol, triglyceride, alkaline phosphatase (ALP), urine parameters, and pro-inflammatory cytokines. The application of DoE (design of experiments) for the optimization of the nanoparticles established a controlled release formulation for diabetes, which displayed safety and effectiveness in streptozotocin (STZ)-induced diabetic rats.

Cardioprotective antihyperglycemic drugs ameliorate endoplasmic reticulum stress.

Cellular stress, notably oxidative, inflammatory, and endoplasmic reticulum (ER) stress, is implicated in the pathogenesis of cardiovascular disease. Modifiable risk factors for cardiovascular disease such as diabetes, hypercholesterolemia, saturated fat consumption, hypertension, and cigarette smoking cause ER stress whereas currently known cardioprotective drugs with diverse pharmacodynamics share a common pleiotropic effect of reducing ER stress. Selective targeting of oxidative stress with known antioxidative vitamins has been ineffective in reducing cardiovascular risk. This "antioxidant paradox" is partially attributed to the unexpected aggravation of ER stress by the antioxidative agents used. In contrast, some of the contemporary antihyperglycemic drugs inhibit both oxidative stress and ER stress in human coronary artery endothelial cells. Unlike sulfonylureas, meglitinides, α glucosidase inhibitors, and thiazolidinediones, metformin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors are the only antihyperglycemic drugs that reduce ER stress caused by pharmacological agents (tunicamycin) or hyperglycemic conditions. Clinical trials with selective ER stress modifiers are needed to test the suitability of ER stress as a therapeutic target for cardiovascular disease.

"Green" synthesized versus chemically synthesized zinc oxide nanoparticles: In vivo antihyperglycemic activity and pharmacokinetics.

Zinc is one of the most studied trace elements, commonly used as supplement in diabetes treatment. By its involvement in the synthesis, secretion of insulin, promotion of insulin sensitivity and its multiple enzymatic functions it is known to contribute to reduce hyperglycemia. Researchers have shown that zinc administered under the form of zinc oxide nanoparticles (ZnONPs) is more effective than under its ionic form. Studies evaluating the antihyperglycemic activity of these nanocarriers include both ZnONPs synthesised using plants (i.e. green synthesized) or chemically synthesized. The present work aims to compare green synthesized ZnONPs with the marketed chemically synthesized ones. Green ZnONPs were synthesized using the aqueous extract of the stem bark of the medicinal plant Panda oleosa and zinc nitrate hexahydrate. Both nanocarriers were compared in terms of optical properties, morphology, composition, chemical functions, resistance to oxidation, in vivo antihyperglycemic activity via oral glucose tolerance test (OGTT) and pharmacokinetics in relation to zinc in C57BL/6J mice. A UV absorption peak was observed at 354 nm and 374 nm for the green and marketed ZnONPs, respectively. The shape and hydrodynamic diameters were anisotropic and of 228.8 ± 3.0 nm for the green ZnONPs and spherical and of 225.6 ± 0.9 nm for the marketed ZnONPs. Phenolic compounds accounted for 2.58 ± 0.04% of the green ZnONPs and allowed them to be more stable and unaffected by an oxidizing agent during the experiment, while the marketed chemically synthesized ZnONPs aggregated with or without contact with an oxidizing agent. No significant differences were observed on the amounts of zinc absorbed when comparing green ZnONPs, chemically synthesized ZnONPs and zinc sulfate in a pharmacokinetics study in normoglycemic mice. When evaluating the in vivo hypoglycemic activity of the nanocarriers in obese/diabetic mice, green synthesized ZnONPs displayed a significant hypoglycemic effect compared with the chemically synthesized nanoparticles following an OGTT. Altogether, these data indicate that phytocompounds, as catechin derivatives and polyphenols, attached to the green synthesized ZnONPs' surface, could contribute to their hypoglycemic activity. The comparison thus demonstrated that green synthesized ZnONPs are significantly more efficient than chemically ones at reducing hyperglycemia regardless of their absorption.

Comparative metabolic study of the chloroform fraction of three Cystoseira species based on UPLC/ESI/MS analysis and biological activities.

This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The results revealed the identification of 19, 20 and 11 metabolites in C. myrica, C. trinodis, and C. tamariscifolia, respectively mainly terpenoids, flavonoids, phenolic acids and fatty acids. Also, an in vitro antioxidant study using FRAP and DPPH assays was conducted where the chloroform fraction of C. trinodis displayed the highest antioxidant activity in both assays, which would be attributed to its highest total phenolics and total flavonoids. Besides, the investigation of COX-1, α-glucosidase and α-amylase inhibitory activities were performed. Regarding C. trinodis, it showed the strongest inhibitory activity towards COX-1. Moreover, it showed potent inhibitory activity towards α-glucosidase and α-amylase enzymes. According to the molecular docking studies, the major compounds characterised showed efficient binding to the active sites of the target enzymes.

Hydrocotyle umbellata L.; a natural source of bioactives to mitigate diabetes mellitus and its complications.

Metabolomics study of Hydrocotyle umbellata L. revealed the richness of its aerial parts in phenolics primarily; quercetin and its glycoside derivatives, which are well-reported to exert antidiabetic activity owing to their powerful antioxidant capacity. Hence, the antioxidant and antidiabetic potentials of the quercetin standardized ethanolic extract of H. umbellata aerial parts were investigated. The antioxidant activity was examined by using in-vitro 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, while the antidiabetic activity was examined by using in-vitro α-glucosidase inhibitory assay and further confirmed by in-vivo experiments using streptozotocin-induced diabetes in rat model. Interestingly, the standardized ethanolic extract showed significant in-vitro antioxidant activity, and effectively inhibited Saccharomyces cerevisiae α-glucosidase enzyme activity. Moreover, it significantly reduced fasting blood glucose, triglycerides, and cholesterol levels. Thus, H. umbellata is a potential natural candidate to attenuate diabetes mellitus and its altered lipid profile complications, which could be attributed to its quercetin and quercetin glycosides content.