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• The present study focuses on the use of natural substances like vitamin C, folic acid, and lactoferrin to stimulate the phenylpropanoid pathway in germinating fenugreek sprouts. • Among the different genotypes studied, germinated fenugreek sprouts of the IM6 genotype pre-treated with 500 µM vitamin C (T1) demonstrated the highest increase in total phenolic content and antioxidant activity on the 4th day of germination. • The T1-treated IM3 fenugreek sprouts also exhibited the most significant anti-hyperglycemic activity. They were able to inhibit the activities of key enzymes involved in carbohydrate digestion, including α-amylase, α-glucosidase, and invertase under in vitro conditions. • The treatments did not significantly affect the levels of diosgenin and trigonelline in germinating sprouts. These compounds are known for their health benefits and remained relatively stable during germination. • Notably, the quercetin content in T1-treated germinating sprouts continued to increase, even beyond the fourth day of germination. Quercetin is a type of flavonoid with antioxidant properties. • The study established a positive correlation between the increase in total phenol content, especially quercetin, and the antioxidant potential as well as anti-diabetic activity observed in the 4th day germinated sprouts. • These findings suggest that using T1-treated fenugreek sprouts may be a promising dietary approach for managing diabetes-related hyperglycemia and oxidative stress. The present study investigated the use of natural elicitors (vitamin C, folic acid, and lactoferrin) to stimulate the phenylpropanoid pathway in germinating fenugreek sprouts, with the aim of increasing their total phenolic phytochemical compounds responsible for imparting antioxidant and anti-hyperglycemic properties. Observations revealed that germinating fenugreek sprouts of the IM3 genotype, pre-treated with 500 µM vitamin C (T1) on the 4th day, exhibited maximal elicitation of total phenolic content (3680 mg/100 g DW) and antioxidant activity (2607.5 µM/100 g DW) compared to other genotypes. Moreover, T1-treated IM3 fenugreek sprouts demonstrated the highest anti-hyperglycemic activity by inhibiting α-amylase (48.96%), α-glucosidase (92.60%), and invertase (45.65%) enzyme activities under in vitro conditions. Interestingly, the selected treatments did not affect the diosgenin and trigonelline content of germinating sprouts, which decreased in a time-dependent manner during germination. However, the quercetin content (0.01365%) of T1-treated germinating sprouts continued to increase appreciably, even after the 4th day of germination. A direct positive correlation was established between the increase in total phenols, especially quercetin, and the antioxidant potential as well as the anti-hyperglycemic activity in germinated fenugreek sprouts on the 4th day. Thus, T1-treated sprouts hold promise for managing diabetes-related hyperglycemia and oxidative stress, emphasizing the efficacy of vitamin C in enhancing their bioactive properties. This research pioneers the use of natural elicitors to enhance the health benefits of fenugreek sprouts, notably by identifying an optimal treatment and elucidating quercetin dynamics during germination. Such findings are pivotal for advancing our understanding of sprouting processes and provide valuable insights into the development of therapeutic functional foods. However, further research is necessary to validate their efficacy before considering them as futuristic functional foods. [ABSTRACT FROM AUTHOR]

Protein tyrosine phosphatase 1B (PTP1B) is an important target for diabetes since inhibition of PTP1B offers therapeutic benefits in insulin resistant diabetes. Unfortunately, no drugs are approved or available in market as PTP1B inhibitor and finding of such type of anti-diabetic agents is still in progress. However, computational modeling, based on the interaction between co-crystallized ligand and macromolecular receptor has presented some structural features required for PTPIB inhibitory activity. Considering these structural features of co-crystallized ligand bound with 3D crystal structure of PTP1B receptor we have designed some chalcones and their heterocyclic derivatives as PTP1B inhibitors. Preliminary substituted chalcones have been investigated but only one phenyl ring of these derivatives shows interaction with PTP1B receptor in molecular docking study. To overcome this problem, some heterocyclic derivatives of chalcone have been designed. These heterocyclic derivatives show interactions similar to co-crystallized ligand, which means both terminal rings exhibit interactions with macromolecular receptor in molecular docking study. Moreover, some of the synthesized heterocyclic derivatives of chalcone show potent inhibitory activity when tested in vitro and compound AD-4 ((E)-3-(3-nitrophenyl)-1-(pyridin-4-yl)prop-2-en-1-one) is observed as the most prominent inhibitory agent with 75.06% inhibition of PTP1B. Potent derivative AD-4 also exhibits significant anti-hyperglycemic activity during in vivo evaluation in animal model. [ABSTRACT FROM AUTHOR]

Abstract Background Type II diabetes mellitus is posing a severe health threat throughout the globe due to its associated pathophysiological risks and high mortality rate. Carbohydrate catabolic enzymes, including α-amylase, α-glucosidase and aldose reductase, play an important role in the development of diabetes. The natural or synthetic inhibitors of these enzymes are crucial in reducing diabetes and its related complications. Tinospora cordifolia is a plant of great significance in Ayurveda due to its unique biological activities, including anti-diabetic properties. The present study aims to identify the active constituents of T. cordifolia leaves and evaluate the in vitro inhibitory potential of its ethanol extract constituents against α-amylase, α-glucosidase and aldose reductase activities. Results The ethanolic leaf extract of T. cordifolia inhibited the activities of α-amylase, α-glucosidase and aldose reductase in a dose-dependent manner. It was on par with the standard inhibitors acarbose and quercetin. At 5 mg/ml, the noted % inhibition values of extract were 69.27 ± 0.17, 67.8 ± 0.26 and 62.55 ± 0.24, respectively, for α-amylase, α-glucosidase and aldose reductase. Using GC-MS analysis, neophytadiene, γ-sitosterol, phytol, phytyl palmitate, and phytyl acetate were identified as prominent constituents of the ethanolic extract. Based on molecular docking and ADME analysis, γ-sitosterol was found as the major reactive phytoconstituent, which showed the highest inhibitory potential against α-amylase, α-glucosidase and aldose reductase activities. Conclusions The present study identified γ-sitosterol as triplet inhibitor of α-amylase, α-glucosidase and aldose reductase and affirmed the ethno-medicinal significance of T. cordifolia leaves in the development of new anti-diabetic leads.

Background The prevalence of diabetes mellitus (DM) is increasing overtime, potentially leading to various severe health complications and mortality. Despite therapeutic agents have currently been developed, unexpected adverse effects are inevitable. Hence, safe and effective medications such as those of plant origin are critical to prevent unexpected complication in DM sufferers. Etlingera elatior has been widely used as spice and traditional medicine to treat diabetes in Aceh Province, Indonesia. However, study regarding α-glucosidase inhibitory effect of E. elatior growing in Gayo highlands, Aceh, Indonesia, is completely lacking. The aim of this study was to evaluate in vitro α-glucosidase inhibitory effect of E. elatior ethanol extracts (EEEE) growing in Gayo highlands, Aceh Province, Indonesia. Methods Antioxidant activity was determined using DPPH procedure, whereas α-glucosidase inhibition assay was carried out using spectrophotometric method. Data analysis was performed using One-Way Analysis of Variance (ANOVA), followed by Duncan’s multiple range test at α=0.05. Results Phytochemical analysis revealed the presence of total phenolic (TPC), total flavonoid (TFC), and total tannin (TTC) content in all E. elatior plant parts, in which the highest TPC was found in the stem (158.38 GAE/g), whereas the highest TFC and TTC was obtained in the rhizome extracts. The extract of fruit showed the strongest antioxidant activities, followed by the stem and leaf, with IC 50 of 2.381 μg/mL, 6.966 μg/mL, and 19.365 μg/mL, respectively. All E. elatior extracts revealed a significant inhibitory activity against α-glucosidase at the concentration of 500 μg/mL, in which the stem extract showed the most effective α-glucosidase inhibitory effect with IC 50 value of 5.15 μg/mL, suggesting its promising potential as antidiabetic agent. Conclusions This study highlights E. elatior potency as a novel source of antioxidant and natural antidiabetic compounds that are useful for the prevention and treatment of diabetes.

Background: Type II diabetes mellitus is posing a severe health threat throughout the globe due to its associated pathophysiological risks and high mortality rate. Carbohydrate catabolic enzymes, including α-amylase, α-glucosidase and aldose reductase, play an important role in the development of diabetes. The natural or synthetic inhibitors of these enzymes are crucial in reducing diabetes and its related complications. Tinosporacordifolia is a plant of great significance in Ayurveda due to its unique biological activities, including anti-diabetic properties. The present study aims to identify the active constituents of T. cordifolia leaves and evaluate the in vitro inhibitory potential of its ethanol extract constituents against α-amylase, α-glucosidase and aldose reductase activities. Results: The ethanolic leaf extract of T. cordifolia inhibited the activities of α-amylase, α-glucosidase and aldose reductase in a dose-dependent manner. It was on par with the standard inhibitors acarbose and quercetin. At 5 mg/ml, the noted % inhibition values of extract were 69.27 ± 0.17, 67.8 ± 0.26 and 62.55 ± 0.24, respectively, for α-amylase, α-glucosidase and aldose reductase. Using GC-MS analysis, neophytadiene, γ-sitosterol, phytol, phytyl palmitate, and phytyl acetate were identified as prominent constituents of the ethanolic extract. Based on molecular docking and ADME analysis, γ-sitosterol was found as the major reactive phytoconstituent, which showed the highest inhibitory potential against α-amylase, α-glucosidase and aldose reductase activities. Conclusions: The present study identified γ-sitosterol as triplet inhibitor of α-amylase, α-glucosidase and aldose reductase and affirmed the ethno-medicinal significance of T. cordifolia leaves in the development of new anti-diabetic leads. [ABSTRACT FROM AUTHOR]

Pulses, as an important part of the human diet, can act as a source of high-quality plant proteins. Pulse proteins and their hydrolysates have shown promising results in alleviating metabolic syndrome and modulating the gut microbiome. Their bioactivities have become a focus of research, with many new findings added in recent studies. This paper comprehensively reviews the anti-hypertension, anti-hyperglycemia, anti-dyslipidemia and anti-obesity bioactivities of pulse proteins and their hydrolysates in recent in vitro and in vivo studies, which show great potential for the prevention and treatment of metabolic syndrome. In addition, pulse proteins and their hydrolysates can regulate the gut microbiome, which in turn can have a positive impact on the treatment of metabolic syndrome. Furthermore, the beneficial effects of some pulse proteins and their hydrolysates on metabolic syndrome have been supported by clinical studies. This review might provide a reference for the application of pulse proteins and their hydrolysates in functional foods or nutritional supplements for people with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background The prevalence of diabetes mellitus (DM) is increasing overtime, potentially leading to various severe health complications and mortality. Despite therapeutic agents have currently been developed, unexpected adverse effects are inevitable. Hence, safe and effective medications such as those of plant origin are critical to prevent unexpected complication in DM sufferers. Etlingera elatior has been widely used as spice and traditional medicine to treat diabetes in Aceh Province, Indonesia. However, study regarding α-glucosidase inhibitory effect of E. elatior growing in Gayo highlands, Aceh, Indonesia, is completely lacking. The aim of this study was to evaluate in vitro α-glucosidase inhibitory effect of E. elatior ethanol extracts (EEEE) growing in Gayo highlands, Aceh Province, Indonesia. Methods Antioxidant activity was determined using DPPH procedure, whereas α-glucosidase inhibition assay was carried out using spectrophotometric method. Data analysis was performed using One-Way Analysis of Variance (ANOVA), followed by Duncan’s multiple range test at α=0.05. Results Phytochemical analysis revealed the presence of total phenolic (TPC), total flavonoid (TFC), and total tannin (TTC) content in all E. elatior plant parts, in which the highest TPC was found in the stem (158.38 GAE/g), whereas the highest TFC and TTC was obtained in the rhizome extracts. The extract of fruit showed the strongest antioxidant activities, followed by the stem and leaf, with IC50 of 2.381 μg/mL, 6.966 μg/mL, and 19.365 μg/mL, respectively. All E. elatior extracts revealed a significant inhibitory activity against α-glucosidase at the concentration of 500 μg/mL, in which the stem extract showed the most effective α-glucosidase inhibitory effect with IC50 value of 5.15 μg/mL, suggesting its promising potential as antidiabetic agent. Conclusions This study highlights E. elatior potency as a novel source of antioxidant and natural antidiabetic compounds that are useful for the prevention and treatment of diabetes.

The excessive consumption of high-energy dietary sweeteners is largely to blame for the widespread metabolic syndrome around the world. This study is aimed at in vivo evaluations of the ameliorative effects of A. garckeana fruit pulp on metabolic syndrome in Wistar rats. Twenty-four (24) adult male Wistar rats were divided into six (6) groups (n=4). Groups A, B, and C received standard, high-fructose, and 2% A. garckeana fruit pulp-supplemented standard diets, respectively. Groups D, E, and F were fed 5% A. garckeana fruit pulp-supplemented standard, 2% A. garckeana fruit pulp-supplemented high-fructose, and 5% A. garckeana fruit pulp-supplemented high fructose diets. In addition to weekly monitoring of weight changes, activities of serum antioxidant enzymes, lipid profile, and blood glucose level were determined. There were no significant changes in weight gain among the groups throughout the experimental period. Compared with the initial value of blood glucose level, only the group fed high fructose diet had significantly (P

Aloe species are known for the treatment of various conditions including diabetes mellitus, hypocholesteremia, and glycation end products. Nevertheless, the biological activity of Aloe armatissima is yet to be reported. It is a first-time report to evaluate the Aloe armatissima leaves (AAL) extract for its antioxidant, anti-glycation, anti-hyperglycemic, and anti-hyperlipidemic potential. In vitro tests of 1,1-diphenyl-2-picrylhydrazyl for the antioxidant and HSA for the antiglycation activity whereas in vivo models were used to assess the toxicity, antihyperglycemic, and anti-hypercholesteremic effects. The volatile profile was determined via gas chromatography-mass spectrometry. The IC50 values of 116 ± 0.66 (μg/mL) for antioxidant activity and 0.21 ± 0.009 (mg/mL) for antiglycation activity were observed for the AAL extract. The acute toxicity in the animal model revealed a lack of toxicity for the extract. The in vivo models exhibited a dose-dependent hypoglycemic and anti-hyperglycemic effects with significant (P < 0.01) blood glucose levels reduction. Moreover, a profound decrease in serum cholesterol, triglyceride, and LDL along with a significant (P < 0.05) increase in HDL and serum insulin levels was recorded. The statistical analysis demonstrated the values of F (24,125) = 23.95, P = 0.001, effect size = 1.95 (normoglycemic mice), F (24,125) = 143.21, P = 0.001, effect size = 4.79 (glucose loaded mice), and F (24,125) = 82.69, P = 0.001, effect size = 3.6 (diabetic model). GCMS showed the presence of eleven compounds with tetratetracontane (100%), β-sitosterol (27.76), and vitamin E (18.68) in major amounts. The results underscore the extract’s capacity to effectively combat various ailments; however, the active phytochemicals need to be isolated and the pharmacological activities may be established at the molecular level.

Amina Alam Kotha,1,&ast; Shihab Uddin Ahmad,2,3,&ast; Irin Dewan,2 Mohiuddin Ahmed Bhuiyan,2 Fahad Imtiaz Rahman,1 Isa Naina Mohamed,3 Md Selim Reza1 1Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh; 2Department of Pharmacy, School of Medicine, University of Asia Pacific, Dhaka, 1215, Bangladesh; 3Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia&ast;These authors contributed equally to this workCorrespondence: Md Selim Reza, Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh, Email selimreza@du.ac.bd Isa Naina Mohamed, Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur, 56000, Malaysia, Email isanaina@ppukm.ukm.edu.myBackground: Metformin hydrochloride (HCl) microspheres and nanoparticles were formulated to enhance bioavailability and minimize side effects through sustained action and optimized drug-release characteristics. Initially, the same formulation design with different ratios of metformin HCl and Eudragit RSPO was used to formulate four batches of microspheres and nanoparticles using solvent evaporation and nanoprecipitation methods, respectively.Methods: The produced formulations were evaluated based on particle size and shape (particle size distribution (PSD), scanning electron microscope (SEM)), incompatibility (differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR)), drug release pattern, permeation behavior, in vivo hypoglycemic effects, and in vitro anticancer potential.Results: Compatibility studies concluded that there was minimal interaction between metformin HCl and the polymer, whereas SEM images revealed smoother, more spherical nanoparticles than microspheres. Drug release from the formulations was primarily controlled by the non-Fickian diffusion process, except for A1 and A4 by Fickian, and B3 by Super case II. Korsmeyer-Peppas was the best-fit model for the maximum formulations. The best formulations of microspheres and nanoparticles, based on greater drug release, drug entrapment, and compatibility characteristics, were attributed to the study of drug permeation by non-everted intestinal sacs, in vivo anti-hyperglycemic activity, and in vitro anticancer activity.Conclusion: This study suggests that the proposed metformin HCl formulation can dramatically reduce hyperglycemic conditions and may also have anticancer potential.Keywords: microsphere, nanoparticles, permeability, anti-hyperglycemic, anticancer

Background The prevalence of diabetes mellitus (DM) is increasing overtime, potentially leading to various severe health complications and mortality. Despite therapeutic agents have currently been developed, unexpected adverse effects are inevitable. Hence, safe and effective medications such as those of plant origin are critical to prevent unexpected complication in DM sufferers. Etlingera elatior has been widely used as spice and traditional medicine to treat diabetes in Aceh Province, Indonesia. However, study regarding α-glucosidase inhibitory effect of E. elatior growing in Gayo highlands, Aceh, Indonesia, is completely lacking. The aim of this study was to evaluate in vitro α-glucosidase inhibitory effect of E. elatior ethanol extracts (EEEE) growing in Gayo highlands, Aceh Province, Indonesia. Methods Antioxidant activity was determined using DPPH procedure, whereas α-glucosidase inhibition assay was carried out using spectrophotometric method. Data analysis was performed using One-Way Analysis of Variance (ANOVA), followed by Duncan’s multiple range test at α=0.05. Results Phytochemical analysis revealed the presence of total phenolic (TPC), total flavonoid (TFC), and total tannin (TTC) content in all E. elatior plant parts, in which the highest TPC was found in the stem (158.38 GAE/g), whereas the highest TFC and TTC was obtained in the rhizome extracts. The extract of fruit showed the strongest antioxidant activities, followed by the stem and leaf, with IC 50 of 2.381 μg/mL, 6.966 μg/mL, and 19.365 μg/mL, respectively. All E. elatior extracts revealed a significant inhibitory activity against α-glucosidase at the concentration of 500 μg/mL, in which the stem extract showed the most effective α-glucosidase inhibitory effect with IC 50 value of 5.15 μg/mL, suggesting its promising potential as antidiabetic agent. Conclusions This study highlights E. elatior potency as a novel source of antioxidant and natural antidiabetic compounds that are useful for the prevention and treatment of diabetes.

Background Data on the incidence of type 2 non–ST‐segment–elevation myocardial infarction (T2MI) in hospitalized patients with COVID‐19 has been limited to single‐center studies. Given that certain characteristics, such as obesity and type 2 diabetes, have been associated with higher mortality in COVID‐19 infections, we aimed to define the incidence of T2MI in a national cohort and identify pre‐hospital patient characteristics associated with T2MI in hospitalized patients with COVID‐19. Methods and Results Using the national American Heart Association COVID‐19 Cardiovascular Disease Quality Improvement Registry, we performed a retrospective 4:1 matched (age, sex, race, and body mass index) analysis of controls versus cases with T2MI. We performed (1) conditional multivariable logistic regression to identify predictive pre‐hospital patient characteristics of T2MI for patients hospitalized with COVID‐19 and (2) stratified proportional hazards regression to investigate the association of T2MI with morbidity and mortality. From January 2020 through May 2021, there were 709 (2.2%) out of 32 015 patients with T2MI. Five hundred seventy‐nine cases with T2MI were matched to 2171 controls (mean age 70; 43% female). Known coronary artery disease, heart failure, chronic kidney disease, hypertension, payor source, and presenting heart rate were associated with higher odds of T2MI. Anti‐hyperglycemic medication and anti‐coagulation use before admission were associated with lower odds of T2MI. Those with T2MI had higher morbidity and mortality (hazard ratio, 1.40 [95% CI, 1.13–1.74]; P=0.002). Conclusions In hospitalized patients with COVID‐19, those with a T2MI compared with those without had higher morbidity and mortality. Outpatient anti‐hyperglycemic and anti‐coagulation use were the only pre‐admission factors associated with reduced odds of T2MI.

Daucosterol, a natural saponin from Eleocharis dulcis peel, exhibited anti-hyperglycemic properties. This study investigated daucosterol's effects on glycemic control, insulin resistance, and gut microbiota in type 2 diabetic mice. The results demonstrated that daucosterol treatment reduced fasting glucose, improved glucose intolerance and pancreatic islet damage. It decreased HOMA-IR and increased ISI, indicating enhanced insulin sensitivity. Daucosterol supplementation enriched gut microbiota diversity, including reducing Firmicutes and Desulfobacterota while increasing Bacteroidia. This involved an increase in Enterococcus, Akkermansia, Alistipes, Clostridium_sensu_stricto_1, and Odoribacter, coupled with decreased Aerococcus, Desulfovibrio, and Blautia, improved gut health. Uncultured_bacterium_g_Clostridium_sensu_stricto_1 and Bifidobacterium_pseudolongum were identified as major biomarkers. PICRUSt analysis revealed daucosterol improved the pathways of glycan biosynthesis and metabolism, lipid metabolism, carbohydrate metabolism, and some organismal systems. Therefore, daucosterol act as a potential anti-hyperglycemic agent, improving insulin resistance and optimizing gut microbiota to alleviate type 2 diabetes.

Okra is an indigenous vegetable consumed for its sliminess and nutritional benefits. The aim of this study was to assess and compare the in vitro antioxidant, and antidiabetic activities of the seed, bark and whole pod of okra. The total phenolic and total flavonoid contents of the different parts were evaluated according to standard methods. The antioxidant capacity was assessed using the 1,1-diphenyl-2-picrylhdrazyl (DPPH), hydroxyl (OH), and 2,2-azino-bis (3- ethylbenzthiazoline-6-sulphoric acid) (ABTS) radical scavenging assays, ferric reducing antioxidant power (FRAP) assay, and ferrous ion-induced lipid peroxidation assay using standard procedures. The in vitro antidiabetic activity was evaluated using the α-amylase, and αglucosidase inhibitory assays. The whole okra pod exhibited a significantly higher total phenolic content (5.0 mg GAE/g) and enhanced radical scavenging activity compared to both the seed and bark of the pod (p < 0.05). Although, the seed had a higher content of total flavonoid (2.23 mg QE/g) than the bark and whole pod, the bark and whole pod of okra showed a higher ferric reducing antioxidant power than the seed. Similarly, the whole pod showed a higher lipid peroxidation inhibition, and higher α-glucosidase inhibitory activity than the bark and seed of the pod. In order to enjoy all the nutritional and pharmacological benefits associated with okra consumption, it is recommended that no part of the pod should be considered a waste. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anti-inflammatory, anti-cancer, anti-parkinsonian, anti-microbial, analgesic, and anti-hyperglycemic properties of a variety of poly-fused pyrimidine derivatives. Methods: A novel series of fused pyrimidine derivatives 1-6 were synthesized by reacting amino pyrazole derivatives with active methylene derivatives to give the corresponding compounds 1-6. Anti-parkinsonian activity was investigated with benzotropene as a reference drug, anti-inflammatory effect in mice was evaluated using carrageenan in paw edema with indomethacin as reference drug, antimicrobial activity was assessed using nutritional agar with ciprofloxacin and ketoconazole as reference drugs, analgesic activity was evaluated using valdecoxib as reference drug, anti-hyperglycemic activity was investigated using alloxan and sucrose models (SLM) with pioglitazone as reference drug and anticancer activity was investigated using the MTT micro-cultured tetrazolium assay method with doxorubicin as reference drug. Results: Pyrimidine derivatives 1-6 possess significant active anti-parkinsonian, anti-inflammatory, antimicrobial, analgesic, anti-hyperglycemic and anticancer activities in comparison to the reference drugs used for each model. Compared to Benzotropene®, compounds 1 and 3 showed a significantly stronger anti-parkinsonian activity (p < 0.03). Compound 3 showed a significantly stronger anti-inflammatory effect than Indomethacin® (p < 0.05). Compounds 5 and 6 exhibited significant anti-microbial activity compared to ciprofloxacin® (p < 0.05). Compounds 4 and 6 exhibited significantly improved analgesic activity as compared to Valdecoxib® (p < 0.01). Compounds 1 and 3 exhibited significantly higher antihyperglycemic effects in SLM model when compared to pioglitazone® (p < 0.02). Compound 5 demonstrated the highest activity against human colon cancer cell line (HT-29) and human prostate cancer cell line (DU145), and also, significantly improved level of efficacy against human lung cancer cell line (A549) compared to Doxorubicin® (p < 0.02). Conclusion: Using the six pyrimidine derivatives 1 - 6 as a lead molecule, a novel class of clinically beneficial anti-cancer, anti-inflammatory, anti-microbial, analgesic, and anti-hyperglycemic drugs may be produced. [ABSTRACT FROM AUTHOR]

Ertugliflozin, a sodium-glucose cotransporter-2 inhibitor, seems to improve glycemic control in type 2 diabetes mellitus (T2DM). We aim to evaluate the efficacy of Ertugliflozin across multiple time intervals (18, 26, and 52 weeks) in T2DM patients. A literature search was conducted on electronic databases. Data was extracted from eligible studies at both 5 mg and 15 mg doses in monotherapy and as add-on therapy. Cochrane RevMan was used to perform the meta-analysis. Ertugliflozin, at both 5 mg and 15 mg doses, demonstrated a significant improvement in HbA1c levels at 18 weeks 5 mg [P = 0.00001], 15 mg [P = 0.05], and at 26 weeks in monotherapy 5 mg [P = 0.006], monotherapy 15 mg [P = 0.006], 5 mg as add-on therapy [P = 0.00001], 15 mg add-on therapy [P = 0.00001] respectively. At 52 weeks, the reduction in HbA1c was significant in 15 mg add-on therapy [P = 0.0001]. Additionally, ertugliflozin as an add-on therapy also led to a significant reduction in FPG, body weight, and systolic blood pressure. Ertugliflozin showed clinical efficacy in improving glycemic control, fasting plasma glucose, body weight, and systolic blood pressure in T2DM patients over the studied time intervals compared to placebo. [ABSTRACT FROM AUTHOR]

The current literature findings on autophagy’s beneficial and detrimental roles in diabetes mellitus (DM) and diabetes-related comorbidities were reviewed. The effects of oral hypoglycaemic medicines and autophagy in DM. Autophagy plays an important function in cellular homeostasis by promoting cell survival or initiating cell death in physiological settings was also assessed. Although autophagy protects insulin-target tissues, organelle failure caused by autophagy malfunction influences DM and other metabolic diseases. Endoplasmic reticulum and oxidative stress enhance autophagy levels, making it easier to regulate stress-induced intracellular changes. Evidence suggests that autophagy-caused cell death can occur when autophagy is overstimulated and constitutively activated, which might prevent or develop DM. Even though the precise role of autophagy in DM complications is uncertain, deregulation of the autophagic machinery is strongly linked to beta cell destruction and the aetiology of DM. Thus, improving autophagy dysfunction is a possible therapeutic objective in treating DM and other metabolic disorders.

Search for natural sources in disease management especially diabetes has surged recently for its potential health benefits. However, several fruit tree species remained unpopular despite their folkloric usage due to insufficient scientific data. Syzygium jambos (L.) Alston (Myrtaceae) is a fruit-bearing plant that is used as a traditional dietary supplement to treat various diseases including diabetes. This study investigated the correlation between S. jambos leaves’ metabolites and the bioactivities using proton-nuclear magnetic resonance (1H NMR)-based metabolomics approach. In-vitro total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH•) radicals scavenging, nitric oxide (NO•) radicals scavenging, anti-α-amylase and anti-α-glucosidase assays were performed. The findings indicated that 70 % ethanolic extract demonstrated the highest potential in overall bioactivities. A total of 59 and 30 metabolites were tentatively identified using ultrahigh-performance liquid chromatography electrospray ionization Quadrupole-Orbitrap tandem mass spectrometry (UHPLC/ESI Q-Orbitrap MS/MS) and NMR, respectively. The partial least square (PLS) model revealed tannins, triterpenoids, and flavonoids significantly contributed to the separation and bioactivities. This study provides comprehensive insights into S. jambos metabolome and reveals the potential as a reliable source of antioxidant and anti-hyperglycemic compounds.

The finest sources of therapeutic agents are natural products, and usnic acid is a secondary metabolite derived from lichen that has a wide range of biological actions, including anti-viral, anti-cancer, anti-bacterial, and anti-diabetic (hyperglycemia). Based on the hyperglycemia activity of UA, this work seeks to identify new anti-hyperglycemia medicines by virtual screening of pyrazole derivatives of UA. Seven hit compounds (Compounds 1, 5, 6, 7, 17, 18 and 33), which finally go through docking-based screening to produce the lead molecule, were identified by the physicochemical attributes, drug-likeliness, and ADMET prediction. The docking score for the chosen compounds containing PPARγ agonists ranged from -7.6 to -9.2 kcal/mol, whereas the docking goal for compounds 5, 6, and 7 was -9.2 kcal/mol. Based on the binding energy and bound amino acid residues as well as compared to the reference compound, compound-6 considered as lead compound. Furthermore, the MD simulation of 3CS8-Compound-6 and 3CS8-Rosiglitazone complexes were performed to verify the stability of these complexes and the binding posture acquired in docking experiments. The compound-6 had strong pharmacological characteristics, bound to the PPARγ agonist active site, and was expected to reduce the activity of the receptor, according to the virtual screening results. It must be justified to conduct both in-vitro and in-vivo experiments to examine the efficacy of this compound. [ABSTRACT FROM AUTHOR]

Sweet potato is a rich source of antioxidant phytohemicals, like β-carotene, vitamin C, anthocyanins, xanthophylls, and phenolics, which are relevant for providing dietary protections against chronic oxidative stress-associated diseases, like type 2 diabetes. However, the health protective phytochemical profiles and associated antioxidant and anti-diabetic properties of sweet potatoes vary widely between different flesh color and among cultivars. Therefore, the aim of this study was to screen aqueous and ethanol (12%) extracts of seven sweet potato cultivars with different flesh colors (white–yellow, orange, and purple) for their phenolic phytochemical-linked functional qualities. Total soluble phenolic (TSP) content, phenolic profile, protein content, total antioxidant activity, anti-hyperglycemic function relevant α-amylase, α-glucosidase, and anti-hypertensive function related angiotensin-I-converting enzyme (ACE) inhibitory activities of sweet potato cultivars were determined using rapid in vitro assay models. The purple flesh cv. NIC-413 had significantly higher phenolic content (2.8 mg GAE 100 g−1 FW) and associated high antioxidant activity. Catechin, gallic, and dihydroxybenzoic acids were found in all cultivars, while chlorogenic acid was present only in purple-flesh cultivar. Anti-hyperglycemic property relevant α-amylase (74–84%), and α-glucosidase (21–60%) enzyme inhibitory activities were present in all sweet potato cultivars. Additionally, anti-hypertensive property relevant ACE (10–88%) enzyme inhibitory activity were present across all sweet potato cultivars. The results of this in vitro screening study suggested that sweet potato cultivars like NIC-413, Murasaki, Evangeline, and Covington are good dietary source of phenolic antioxidants and can be relevant for anti-hyperglycemic and anti-hypertensive benefits to target type 2 diabetes associated health risks. [ABSTRACT FROM AUTHOR]

Data from the International Diabetes Federation revealed annual increases in the prevalence of diabetes mellitus, which require special attention. Implementation of the ‘back to nature’ trend presents opportunities to overcome this problem. As a medicinal plant, Faloak is widely used by people in Nusa Tenggara Timur, Indonesia. This study aimed to evaluate in vivo and in vitro anti-hyperglycemic activity of the bark of Sterculia quadrifida, known as Faloak. In vivo evaluation used sucrose-induced male mice. Measurements of glucose level employed a glucometer and data were analyzed statistically. Demonstrating anti-hyperglycemic activity of the bark of Faloak decoct, results showed doses 1.67 and 3.3 g/kg BW reduced glucose levels by 62.2% and 56.9%, respectively. In vitro examination of Faloak decoct at various concentrations used alpha glucosidase (sucrose) enzymatic reaction. Results of in vitro examinations demonstrated of Faloak bark decoct inhibited alpha glucosidase (sucrose) activity by 42.09 ± 4.39%. Further testing on humans is needed to confirm these findings.

Introduction: Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored. Objectives: To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice. Methods: High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota. Results: The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes, Parabacteroides, Lachnoclostridium, and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus, Alloprevotella, Alistipes, Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation. Conclusion: GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia.

[Display omitted] • Two luteolin derivatives GLQ and GLQ.Cr with hypoglycaemic activity were prepared. • GLQ.Cr affected the PPAR signaling pathway to improve hyperglycaemia symptoms. • GLQ.Cr regulation of intestinal microbiota community was verified by fecal microbiota transplantation. Luteolin is a plant-derived flavonoid that exhibits a broad range of pharmacological activities. Studies on luteolin have mainly focused on its use for hyperlipidaemia prevention, whereas the capacity of the flavonoid to hinder hyperglycaemia development remains underexplored. To probe the anti-hyperglycemic mechanism of 6,8-guanidyl luteolin quinone-chromium coordination (GLQ.Cr), and to assess its regulatory effect on intestinal microbiota in type 2 diabetes mellitus (T2DM) mice. High-sucrose/high-fat diet-induced and intraperitoneal injection of streptozotocin was used to develop a T2DM model. Glycometabolism related indicators, histopathology, and gut microbiota composition in caecum samples were evaluated, and RNA sequencing (RNA-seq) of liver samples was conducted. Faecal microbiota transplantation (FMT) was further used to verify the anti-hyperglycemic activity of intestinal microbiota. The administration of GLQ.Cr alleviated hyperglycaemia symptoms by improving liver and pancreatic functions and modulating gut microbe communities (Lactobacillus, Alistipes , Parabacteroides , Lachnoclostridium , and Desulfovibrio). RNA-seq analysis showed that GLQ.Cr mainly affected the peroxisome proliferative activated receptor (PPAR) signalling pathway in order to regulate abnormal glucose metabolism. FMT significantly modulated the abundance of Lactobacillus , Alloprevotella , Alistipes , Bacteroides, Ruminiclostridium, Brevundimonas and Pseudomonas in the caecum to balance blood glucose levels and counteract T2DM mice inflammation. GLQ.Cr improved the abnormal glucose metabolism in T2DM mice by regulating the PPAR signalling pathway and modulating intestinal microbial composition. FMT can improve the intestinal microecology of the recipient and in turn ameliorate the symptoms of T2DM-induced hyperglycaemia. [ABSTRACT FROM AUTHOR]

The 11 β- hydroxysteroid dehydrogenase 1 (11 β-HSD1) is hypothesized to play a role in the pathogenesis of type 2 diabetes and its related complications. Because high glucocorticoid levels are a risk factor for metabolic disorders, 11β-HSD1 might be a viable therapeutic target. In this investigation, docking experiments were performed on the main constituents of Spondias mangifera (SM) oleanolic acid, β-amyrin, and β-sitosterol to ascertain their affinity and binding interaction in the human 11β-hydroxysteroid dehydrogenase-1 enzyme's active region. The results of in vitro 11β HSD1 inhibitory assay demonstrated that the extract of S. mangifera had a significant (p < 0.05) decrease in the 11-HSD1% inhibition (63.97%) in comparison to STZ (31.79%). Additionally, a non-insulin-dependent diabetic mice model was used to examine the sub-acute anti-hyperlipidemic and anti-diabetic effects of SM fruits. Results revealed that, in comparison to the diabetic control group, SM fruit extract (SMFE) extract at doses of 200 and 400 mg/kg body weight considerably (p < 0.05 and p < 0.01) lowered blood glucose levels at 21 and 28 days, as well as significantly decreased total cholesterol (TC) and triglycerides (TG) and enhanced the levels of high-density lipoprotein (HDL). After 120 and 180 s of receiving 200 and 400 mg/kg SMFE, respectively, disease control mice showed significantly poorer blood glucose tolerance (p < 0.05 and p < 0.01). SMFE extract 200 (p < 0.05), SMFE extract 400 (p < 0.01), and Glibenclamide at a dosage of 5 mg/kg body weight all resulted in statistically significant weight increase (p < 0.01) when compared to the diabetic control group after 28 days of treatment. According to in silico, in vitro, and in vivo validation, SMFE is a prospective medication with anti-diabetic and hypoglycemic effects. [ABSTRACT FROM AUTHOR]

Astilbe rivularis Buch.-Ham. ex D. Don is a rare medicinal plant, traditionally employed for treating several disorders. The juice, decoction or powder of the roots, rhizomes, leaves and even the entire plant, are used for managing peptic ulcer, diarrhoea, jaundice, sprains and muscular swellings, bone fracture and dislocation of joints, postpartum bleeding and other menstrual disorders. These conventional medicinal uses make Astilbe rivularis a promising candidate for further research. This study was designed to explore the neuroprotective potential of hydroethanolic extract of Astilbe rivularis (ARHE) in diabetic neuropathy (DN) in rats. GC-MS analysis was used to identify the phytoconstituents present in the plant extract. DN was induced by administration of STZ (55 mg/kg, i.p.), 15 min after NAD (230 mg/kg, i.p.) injection. The rats with fasting blood glucose (FBG) level >250 mg/dl were included in the study. DN was assessed by estimating the level of FBG, lipid profile, and in vitro and in vivo oxidative stress parameters. Additionally, behavioural parameters like, mechanical hyperalgesia, hot and cold allodynia were estimated to assess diabetic neuropathy. Furthermore, the level of antioxidant enzymes like SOD, GSH, and TBARS in sciatic nerve and inflammatory markers like, TGF-β and IL-6 were measured. Altogether, 30 phytoconstituents were identified including heptafluorobutyric acid, hexadecanoic acid, and beta-sitosterol depicting antioxidant, antidiabetic, and anticancer properties, respectively. Administration of different doses (100, 200, and 400 mg/kg) of ARHE to diabetic rats attenuated elevated blood glucose level and restored lipid profile, body weight, food and water intake, and antioxidant level. Moreover, elevated level of inflammatory markers like, TGF-β and IL-6 was also found to be attenuated in sciatic nerve. Furthermore, ARHE attenuated the pain response assessed by mechanical hyperalgesia and hot and cold allodynia in diabetic neuropathy rats. ARHE also showed inhibitory activity on ALR enzyme and erythrocyte sorbitol accumulation, and ameliorated oxidative stress. Histopathological study indicated improvement in the architecture of sciatic nerve tissue in diabetic neuropathy rats with the treatment of ARHE. Conclusively, hydroethanolic extract of Astilbe rivularis exhibited neuroprotective potential and ameliorated diabetic neuropathy in rats. [Display omitted] • Astilbe rivularis (ARHE) is a rare traditional plant recognized for its various medicinal properties. • ARHE inhibited aldose reductase in vitro , reducing erythrocyte sorbitol levels and showing potent antioxidant activity. • ARHE reduced blood glucose, restored lipid profile, and alleviated neuropathic pain with anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Traditional fermented foods with unique nutritional profiles are affordable and accessible dietary sources that support basic nutritional needs of many communities around the world. Ogi is a fermented combined cereal (Maize/Sorghum/other Millets) -based food of Nigeria and Sub-Saharan Africa, widely used as breakfast food for adults and weaning food for infants. However, during Ogi processing from cereal grains into slurries, significant losses of essential nutrients occurs, which affect overall nutritional quality. Therefore, improving specific health-targeted functional qualities of Ogi using novel food synergies with local plant based edible sources that are rich in essential nutrients and other health protective bioactives have significant dietary and health relevance. In this study, locally grown underutilized edible plants, like tigernut (Cyperus esculentus) and sesame (Sesamum indicum L.) seeds in different proportions (20 and 30 g) were separately synergized into maize and sorghum (80 and 70 g) and these food synergies were allowed to ferment spontaneously for 48 h. Physiochemical properties, proximate composition, and microbial population count of fermented food synergies were investigated at 0, 24, and 48 h time points. Additionally, total soluble phenolic content, phenolic profile, antioxidant activity, and anti-hyperglycemic property relevant α-glucosidase enzyme inhibitory activity of dried fermented food synergies were determined using rapid in vitro assay models. Food synergy with sesame seeds and natural fermentation resulted in improvement of crude protein, fat, and vitamin C content in both maize and sorghum based Ogi. Furthermore, higher soluble phenolic content and high antioxidant activity were observed in food synergies with sesame seeds and specifically after 24 h of fermentation. High anti-hyperglycemic property relevant α-glucosidase enzyme inhibitory activity was also observed in fermented sorghum synergized with sesame seeds and tigernut. Therefore, integration of food synergy into traditional fermentation process is an effective bioprocessing strategy to improve overall nutritional profile and human health protective functional qualities in cereal-based fermented foods like Ogi targeting dietary and health benefits of wider communities.

Abstract The anecdotal use of Alternanthera sessilis L. as a relief for diabetes has been known in the Philippines for generations, and antidiabetic activity of similar varieties in other countries is likewise documented. However, the compounds responsible for this activity remain unclear. This study aims to isolate the anti-hyperglycemic fraction of local A. sessilis leaves and identify the compounds in this fraction. Methanol extract of A. sessilis leaves and its hexane, ethyl acetate (ASE), and water fractions were administered to alloxan-induced diabetic mice. ASE (250mg/kg) had the highest anti-hyperglycemic activity at 6-h post-treatment (25.81%±12.72%), with almost similar blood glucose reduction rate as metformin (30.13±3.75%, p=0.767). Repeated fractionation employing chromatographic separation techniques followed by in vivo anti-hyperglycemic assay yielded partially purified subfractions. A. sessilis ethyl acetate subfraction 4-2 (100mg/kg) displayed remarkable suppression of blood glucose rise in diabetic mice at 6-h post-treatment (26.45±3.75%, p

Diabetes mellitus is a disease related to hyperglycemia and insulin resistance that can lead to the outcome of chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD). Red betel leaves are known as traditional plants that have antihyperglycemic potential. This study aimed to investigate the effect of ethanolic extract of red betel leaves nanoparticle (RbL-Nps) on the liver and hepatic insulin receptor's (INSR) expression in diabetic rats. Thirty rats were included in this study and further divided into five groups containing six rats each. Group I (GI) comprised of the normal rats; while group II (GII), III (GIII), IV (GIV) and V (GV) comprised of diabetic rats induced by streptozotocin (STZ) at dose of 45 mg/kg bw and nicotinamide (NA) at dose of 110 mg/kg bw, intraperitoneally. Group I and II were treated with 0,5% Na-CMC orally. Group III, IV and V were given the oral administration of RbL-Nps at the doses 30, 60, and 90 mg/kg bw diluted in 0,5% Na-CMC, respectively. All groups were treated once daily and subsequently euthanized after 28 days. Liver tissues were collected for immunohistochemistry method to see the INSR expression and haematoxylin-eosin (HE) staining. Result in this study revealed that INSR expression on the GI, GIII and GIV were significantly higher compared to that on the GII (p < 0.05). On the other hand, there were no significant differences on the INSR expression between GV and GII (p > 0.05). Histologically, liver tissues retrieved from GII showed severe vacuolic and necrotic hepatocytes with dilatated sinusoid. Mild vacuolic and necrotic hepatocytes were observed from GV. There were no pathological changes observed in the liver tissues retrieved from GI, GII, and GIV. We concluded that RbL-Nps improved the liver condition of diabetic rats at doses of 30 and 60 mg/ kg bw, but not at doses of 90 mg/kg bw. [ABSTRACT FROM AUTHOR]

Context: Ammodaucus leucotrichus commonly known as a ‘Kamune es sufi or akâman’ in Morocco, is used to treat many diseases including diabetes. Aims: To investigate the antihyperglycemic activity of an aqueous extract of fruits A. leucotrichus (AEAL) and its chemical composition. Methods: The antihyperglycemic effect of the AEAL was tested against intestinal α-glucosidase and pancreatic α-amylase activities, in vitro, at the concentrations (41-328 µg/mL) and (0.5-3 mg/mL) respectively. In addition, the inhibitory effect of the AEAL (150 mg/kg) against these enzymes was confirmed, in vivo in normal and alloxan diabetic rats using sucrose, starch, and glucose as a substrate.The antihyperglycemic effect of the AEAL was also tested against intestinal D-glucose absorption activity at the dose of 150 mg/kg using the jejunum segment perfusion technique, in situ. Chemical composition was evaluated using HPLC. Results: The results of this study showed that the AEAL was significantly (p

Abstract Background Jatropha gossypiifolia L. is a widespread plant in tropical and sub-tropical countries used in traditional medicine. This study investigated the anti-diuretic and anti-hyperglycemia activities of J. gossypiifolia leave extract on streptozotocin-induced diabetic rats. Methods The leaves was shade dried, pulverized and prepared into extract. 30, 50 and 100 mg/kg of the leaves extracts of J. gossypiifolia was subject to diuretics and hyperglycemic properties using established protocol of diuretic and diabetes test on the rat bladders emptied via mild compression in the pelvic region and gently pulling of their tails. 0.5 ml/kg normal saline, reference drug and the tested were administered with a single dose of the various drugs, and Streptozotocin (STZ) was freshly prepared in 0.1 M citrate buffer with pH 4.5 prior to induction, animals were fasted 24 h and single dose of 45 mg STZ per kg body weight was administered intraperitoneally. Urine and blood samples were isolated from rats and centrifuged for the determination of renal function test. Diuretic and antidiabetic indexes where evaluated using adopted method. Results This study showed that, graded doses of the extract significantly increased diuretic effect, specifically at 100 mg/kg increased diuretic index at 4.29 and urine volume 5.06 and 10 mg/kg Hydrochlorothiazide with 6.23 ml when compared untreated group (1.18 ml) (p 0.05). Also, the extract maintained a normal body mass indexes, biochemical and anatomical structure. Conclusion The effect associated with J. gossypiifolia potentiated its anti-diuretic and anti-hyperglycemic properties as early stated in the ethnomedicinal reports.

Plant polyphenol supplementation may improve fish health in aquaculture systems. To assess the potential benefits and function mechanism of plant polyphenols in aquaculture, fish were fed either basal feed (CON) or the basal feed supplemented with 500 mg/kg of curcumin (CUR), oligomeric proanthocyanidins (OPC), chlorogenic acid (CGA), or resveratrol (RES). After an 8-week feeding experiment, blood samples were used to analyze the concentrations of biochemical indices. Gut samples were collected to evaluate microbiota, short chain fatty acid (SCFA) levels, and gene expression. The results indicated that polyphenol administration reduced serum glucose and insulin. Lysozyme activity was enhanced by OPC and CGA, and superoxide dismutase activity was increased by CUR, OPC, and CGA. The gut microbial structure of the RES group was segregated from that of the CON, and the genus Bacteroides was identified as a potential biomarker in the CUR, CGA, and RES groups. Total gut SCFA increased in the CUR, CGA, and RES groups. A strong correlation was observed between Bacteroides and SCFA. In conclusion, dietary polyphenols have distinct anti-inflammatory, anti-oxidant, and anti-hyperglycemic activities that may be closely associated with their microbiota-modulation effects. [ABSTRACT FROM AUTHOR]

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 μg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 μg/mL and mild activity in the β-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 μg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 μg GAE/mg) and flavonoids (24.30 ± 0.44 μg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research. [ABSTRACT FROM AUTHOR]

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New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.2, 73.9, 71.4, 67.3, 62, 60.7, 58.4, and 55.9%, respectively, while the reference glibenclamide had 55.4%. Compounds IV-1, VI-2-a, IV-2, V, and IV-6 showed more prolonged antidiabetic activity than glibenclamide. Moreover, molecular docking and pharmacokinetic studies were performed to examine binding modes of the prepared compounds against peroxisome proliferator-activated receptor gamma (PPARγ). The highest active compounds exhibited good binding affinity with high free energy of binding against PPARγ. In silico absorption, distribution, metabolism, elimination and toxicity (ADMET) studies were performed to investigate pharmacokinetics and safety of the synthesized compounds. They showed considerable human intestinal absorption with low toxicity profile. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and a major cause of end-stage kidney disease (ESKD). The pathogenesis of DKD is very complex and not completely understood. Recently, accumulated evidence from in vitro and in vivo studies has demonstrated that inflammation plays an important role in the pathogenesis and the development of DKD. It has been well known that a variety of pro-inflammatory cytokines and related signaling pathways are involved in the procession of DKD. Additionally, some anti-hyperglycemic agents and mineralocorticoid receptor antagonists (MRAs) that are effective in alleviating the progression of DKD have antiinflammatory properties, which might have beneficial effects on delaying the progression of DKD. However, there is currently a lack of systematic overviews. In this review, we focus on the novel pro-inflammatory signaling pathways in the development of DKD, including the nuclear factor kappa B (NF-κB) signaling pathway, toll-like receptors (TLRs) and myeloid differentiation primary response 88 (TLRs/MyD88) signaling pathway, adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathways, inflammasome activation, mitochondrial DNA (mtDNA) release as well as hypoxia-inducible factor-1(HIF-1) signaling pathway. We also discuss the related anti-inflammation mechanisms of metformin, finerenone, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, Dipeptidyl peptidase-4 (DPP-4) inhibitors, Glucagon-like peptide-1 (GLP-1) receptor agonist and traditional Chinese medicines (TCM). [ABSTRACT FROM AUTHOR]

Introduction: Pinus halepensis is a medicinal plant used in traditional medicine for treatment of various pathologies including diabetes. The objective of this study is to perform a phytochemical study and to evaluate the antioxidant and antidiabetic activities of extracts of the bark of P. halepensis. Methods: Total polyphenols, flavonoids and tannins were determined by the Folin Ciocalteu method, aluminum trichloride reagent (AlCl3) and vanillin assay. Evaluation of the antioxidant activity was carried out using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2’-azinobis- (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing agent (ferric reducing). The antidiabetic activity was first revealed by enzymatic inhibition tests through measuring the residual activities of α-amylase and α-glucosidase, and then, by oral tolerance tests of glucose and starch in male Wistar rats. To verify the safety of plant extracts, acute oral toxicity was determined. Results: The phytochemical analysis showed that the extracts of P. halepensis were rich in phenolic compounds. The anti-oxidation activity tests revealed a significant reducing power towards the radicals tested. In addition, P. halepensis inhibited the enzymes involved in diabetes (α-amylase and α-glucosidase) at very low concentrations. These effects were verified in the in vivo approach, in particular by using the starch tolerance test. Conclusion: P. halepensis extracts showed remarkable antioxidant and antidiabetic effects. However, further investigations are necessary to identify the main compounds of P. halepensis and to evaluate their antioxidant and antidiabetic effects.

Context: Saraca asoca (Leguminosae) has been widely used in the Ayurvedic system of medicine for various ailments, and it has been used to treat diabetes as a folk medicine. Aims: To investigate the anti-hyperglycemic and anti-hyperlipidemic effect of ethanolic extracts of S. asoca (EESA) flowers in alloxan-induced diabetic rats. Methods: The anti-hyperglycemic activity of EESA was evaluated by using normal and alloxan-induced (120 mg/kg, i.p.) diabetic rats. In the sub-chronic animal model of diabetes mellitus, EESA was orally administered to normal and alloxan-induced-diabetic rats at doses of 200 and 400 mg/kg p.o. per day for 28 days. Results: Fasting blood glucose (FBG), insulin, glycated hemoglobin (HbA1c) levels, lipid profiles, alkaline phosphatase (ALP), and body weights were monitored at the end of 28 days in the EESA treated diabetic rats. The anti-hyperglycemic effect of EESA was more pronounced at the doses of 200 and 400 mg/kg in alloxan-treated diabetic rats as compared with vehicle-treated rats. EESA also showed a significant (p

Meretrix lusoria (M. lusoria) is an economically important shellfish which is widely distributed in South Eastern Asia that contains bioactive peptides, proteins, and enzymes. In the present study, the extracted meat content of M. lusoria was enzymatic hydrolyzed using four different commercial proteases (neutrase, protamex, alcalase, and flavourzyme). Among the enzymatic hydrolysates, M. lusoria protamex hydrolysate (MLPH) fraction with MW ≤ 1 kDa exhibited the highest free radical scavenging ability. The MLPH fraction was further purified and an amino acid sequence (KDLEL, 617.35 Da) was identified by LC-MS/MS analysis. The purpose of this study was to investigate the anti-obesity and anti-hyperglycemic effects of MLPH containing antioxidant peptides using ob/ob mice. Treatment with MLPH for 6 weeks reduced body and organ weight and ameliorated the effects of hepatic steatosis and epididymal fat, including a constructive effect on hepatic and serum marker parameters. Moreover, hepatic antioxidant enzyme activities were upregulated and impaired glucose tolerance was improved in obese control mice. In addition, MLPH treatment markedly suppressed mRNA expression related to lipogenesis and hyperglycemia through activation of AMPK phosphorylation. These findings suggest that MLPH has anti-obesity and anti-hyperglycemic potential and could be effectively applied as a functional food ingredient or pharmaceutical. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-4 is an integral membrane serine exopeptide catalyzing the deactivation of incretin hormones, which are important physiological substrates to release insulin from pancreatic beta cells and augmenting glucagon production, and thus, regulating postprandial hyperglycemia. Undescribed γ-pyrone enclosed macrocyclic poyketides ellipyrones A-B were purified from the crude solvent extract of marine cuttlefish, Sepia elliptica by repeated chromatographic fractionation. Ellipyrone A showed greater inhibition potential against dipeptidyl peptidase-4 (IC50 0.35 mM) than that demonstrated by ellipyrone B (IC50 0.48 mM), and was proportionate with those exhibited by reference dipeptidyl peptidase inhibitor diprotin A (IC50 0.29 mM). Ellipyrone A also recorded commensurate anti-carbolytic property against α-glucosidase (IC50 0.74 mM) and α-amylase (IC50 0.59 mM) when compared with anti-hyperglycemic agent acarbose. Greater structural descriptors of ellipyrone A (topological surface area of 116.2) in conjunction with permissible hydrophobic criterion (n-octanol-water partition ratio of 0.37) further attributed its prospective dipeptidyl peptidase attenuation property owing to the transcelluar mechanism involved in the antidiabetic drug action. These isolated γ-pyrone fused macrocyclic poyketides could be used as pharmaco-active food supplement against hyperglycemia-associated ailments. [ABSTRACT FROM AUTHOR]

Abstract Background Acacia modesta Wall. (A. modesta), often recognized as Phulai, is belonging to family Fabaceae and sub-family Mimosaceae. A. modesta has many beneficial uses. Leaves, wood, flowers, and gum of A. modesta have been used frequently for multiple therapeutic purposes. Results The chemical investigation of butanol fraction of A. modesta non-flowering aerial parts yielded Vitexin-2′′-β-D-glucopyranoside and Apigenin-6,8-di-C-β-D-glucopyranoside in a flavone mixture as well as (β-D-glucopyranosyl (1-3)-β-D-glucopyranosyl)-3-β-hydroxy-11-oxo-olean-12-en-28-oic acid) an oleanane-type triterpenoidal saponin. Metabolite profiling via ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) of the ethyl acetate fraction resulted in recognizing of eighteen compounds tentatively compared with previously published data. Quantitative measurement of the overall value of flavonoids of A. modesta was found to be 2.824 μg/100 μg ± 0.01 calculated as quercetin. The acute toxicity study of the ethanol extract proved that the plant under investigation is safe and nontoxic to the male albino mice used. The anti-hyperglycemic activity of the ethanol extract performed on type 2 diabetic rats proved that the most potent dosage was 200 mg/kg b. wt. after 4 and 4 weeks of treatment respectively compared to metformin. Furthermore, evaluation of the hepato-protective activity of the ethanol extract of the plant under investigation showed that the most potent extract was with a dose level of 200 mg/kg b. wt. after 3 and 10 days of continuous treatment compared to silymarin. Conclusion It can be concluded that A. modesta Wall. cultivated in Egypt could be used as a promising anti-diabetic agent and a hepato-protective agent against hepatocellular damage induced by hepatotoxins.

The present study aimed to evaluate the effects of chrysoeriol from Cardiospermum halicacabum in streptozotocin induced Wistar rats. Thirty rats were categorized as control, diabetic control supplemented with 0, 20 mg/kg chrysoeriol and 600 μg/kg BW of glibenclamide for 45-day trial period. Our results indicated that the inclusion of chrysoeriol (20 mg/kg), showed a significant reduction in plasma glucose, hemoglobin and glycosylated hemoglobin level with a rising of plasma insulin sensitivity. Further, downregulated enzymes including glucose 6-phosphatase, fructose 1,6-bisphosphatase, and glycogen phosphorylase as well upregulated enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, pyruvate kinase, and hepatic glycogen content. There was a diminish action found in liver glycogen synthase of tested rat with a rise in gamma-glutamyl transpeptidase, towards normal levels upon treatment with chrysoeriol. The histopathological study confirmed that renewal of the beta cells of pancreatic of chrysoeriol and glibenclamide treated rats. In addition, the molecular docking of chrysoeriol against glycolytic enzymes including hexokinase, glucose-6-phosphate dehydrogenase, pyruvate kinase, using Argus software shows chrysoeriol had greatest ligand binding energy as equivalent to glibenclamide, as a standard drug. Thus, chrysoeriol found to be non-toxic with potential regulation on glycemic control and upregulation of the carbohydrate metabolic enzymes.

Introduction: The sodium-glucose co-transporter 2 (SGLT2) inhibitors are FDA-approved class of drugs for diabetes management. They improve glycemic control by inducing glucosuria. Notwithstanding with potent anti-hyperglycemic activity, SGLT2 inhibitors are emerging as drugs with multifaceted therapeutic potential, evidenced for cardioprotective, renoprotective, antihypertensive, and neuroprotective activities. Continuous attempts are being accomplished through structural modification, development of new formulation, or combination with other drugs, to enhance the bioactivity spectrum of SGLT2 inhibitors for better management of diabetes and related complications., Areas Covered: This review comprises a summary of patent applications, acquired using the Espacenet Patent Search database, concerning SGLT2 inhibitors from 2019 to 2023, with focus on improving therapeutic potentials in management of diabetes and metabolic complications., Expert Opinion: SGLT2 inhibitors have provided an exciting treatment option for diabetes. Originally developed as anti-hyperglycemic agents, SGLT2 inhibitors exert pleiotropic metabolic responses and have emerged as promising antidiabetic agents with cardio-protective and reno-protective activities. Given their distinct therapeutic profile, SGLT2 inhibitors have revolutionized the management of diabetes and associated complications. Emerging evidences on their therapeutic potential against cancer, male reproductive dysfunctions, and neurodegenerative diseases indicate that further research in this field may unfold novel prospective on their plausible use in the management of other chronic conditions.