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1.
Drug Des Devel Ther ; 18: 3825-3839, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39219697

RESUMO

Background: The twigs and roots of Erythrina subumbrans (Hassk). Merr. Was reported to possess antidiabetic activity by reducing the activity of α-glucosidase and α-amylase. TNF-α is a pro-inflammatory cytokine in obesity and diabetes mellitus (DM). It inhibits the action of insulin, causing insulin resistance. Adiponectin is an anti-inflammatory peptide synthesized in white adipose tissue (WAT) and its high levels are linked with a decreased risk of DM. However, information about the effect of Erythrina subumbrans (Hassk). Merr. on insulin resistance are still lacking. Purpose: To obtain the effects of the ethanol extract of E. subumbrans (Hassk) Merr. leaves (EES) in improving insulin resistance conditions. Methods: The leaves were collected at Ciamis, West Java, Indonesia, and were extracted using ethanol 96%. The effects of EES were studied in fructose-induced adult male Wistar rats by performing the insulin tolerance test (ITT) and assessing blood glucose, TNF-α, adiponectin, and FFA levels. The number of WAT and BAT of the adipose tissues was also studied. The total phenols and flavonoids in EES were determined by the spectrophotometric method and the presence of quercetin in EES was analyzed using the LC-MS method. Results: EES significantly reduced % weight gain, TNF-α levels, and increased adiponectin levels in fructose-induced Wistar rats. EES significantly reduced the FFA levels of fructose-induced Wistar rats and significantly affected the formation of BAT similar to that of metformin. All rats in EES and metformin groups improved insulin resistance as proven by higher ITT values (3.01 ± 0.91 for EES 100 mg/kg BW; 3.01 ± 1.22 for EES 200 mg/kg BW; 5.86 ± 3.13 for EES 400 mg/kg BW; and 6.44 ± 2.58 for metformin) compared with the fructose-induced group without treatment (ITT = 2.62 ± 1.38). EES contains polyphenol compounds (2.7638 ± 0.0430 mg GAE/g extract), flavonoids (1.9626 ± 0.0152 mg QE/g extract), and quercetin 0.246 µg/mL at m/z 301.4744. Conclusion: Erythrina subumbrans (Hassk). Merr. extract may have the potential to be further explored for its activity in improving insulin resistance conditions. However, further studies are needed to confirm its role in alleviating metabolic disorders.


Assuntos
Erythrina , Frutose , Resistência à Insulina , Extratos Vegetais , Ratos Wistar , Animais , Ratos , Masculino , Erythrina/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Frutose/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Folhas de Planta/química , Relação Dose-Resposta a Droga
2.
Int J Mol Sci ; 25(9)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38732125

RESUMO

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.


Assuntos
Células 3T3-L1 , Adipócitos , Adipogenia , Fármacos Antiobesidade , Hipoglicemiantes , PPAR gama , Extratos Vegetais , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Adipogenia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , PPAR gama/metabolismo , PPAR gama/genética , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína alfa Estimuladora de Ligação a CCAAT/genética , alfa-Glucosidases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/farmacologia , Inibidores de Glicosídeo Hidrolases/farmacologia , Crassulaceae/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos
3.
SAR QSAR Environ Res ; 35(5): 411-432, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38764437

RESUMO

Phytochemicals are now increasingly exploited as remedial agents for the management of diabetes due to side effects attributable to commercial antidiabetic agents. This study investigated the structural and molecular mechanisms by which betulinic acid exhibits its antidiabetic effect via in vitro and computational techniques. In vitro antidiabetic potential was analysed via on α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin inhibitory assays. Its structural and molecular inhibitory mechanisms were investigated using Density Functional Theory (DFT) analysis, molecular docking and molecular dynamics (MD) simulation. Betulinic acid significantly (p < 0.05) inhibited α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin enzymes with IC50 of 70.02 µg/mL, 0.27 µg/mL, 1.70 µg/mL and 8.44 µg/mL, respectively. According to DFT studies, betulinic acid possesses similar reaction in gaseous phase and water due to close values observed for highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) and the chemical descriptors. The dipole moment indicates that betulinic acid has high polarity. Molecular electrostatic potential surface revealed the electrophilic and nucleophilic attack-prone atoms of the molecule. Molecular dynamic studies revealed a stable complex between betulinic acid and α-amylase, α-glucosidase, pancreatic lipase and α-chymotrypsin. The study elucidated the potent antidiabetic properties of betulinic acid by revealing its conformational inhibitory mode of action on enzymes involved in the onset of diabetes.


Assuntos
Ácido Betulínico , Quimotripsina , Hipoglicemiantes , Lipase , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Triterpenos Pentacíclicos , alfa-Amilases , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , alfa-Amilases/química , Lipase/antagonistas & inibidores , Lipase/química , Lipase/metabolismo , Quimotripsina/antagonistas & inibidores , Quimotripsina/metabolismo , Triterpenos/química , Triterpenos/farmacologia , Relação Quantitativa Estrutura-Atividade , alfa-Glucosidases/metabolismo , alfa-Glucosidases/química , Diabetes Mellitus/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química
4.
Int J Biol Macromol ; 265(Pt 1): 130713, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471612

RESUMO

Rapeseed-derived peptides (RPPs) can maintain the homeostasis of human blood glucose by inhibiting Dipeptidyl Peptidase-IV (DPP-IV) and activating the calcium-sensing receptor (CaSR). However, these peptides are susceptible to hydrolysis in the gastrointestinal tract. To enhance the therapeutic potential of these peptides, we developed a chitosan/sodium alginate-based nanocarrier to encapsulate two RPP variants, rapeseed-derived cruciferin peptide (RCPP) and rapeseed-derived napin peptide (RNPP). A convenient three-channel device was employed to prepare chitosan (CS)/sodium alginate (ALG)-RPPs nanoparticles (CS/ALG-RPPs) at a ratio of 1:3:1 for CS, ALG, and RPPs. CS/ALG-RPPs possessed optimal encapsulation efficiencies of 90.7 % (CS/ALG-RNPP) and 91.4 % (CS/ALG-RCPP), with loading capacities of 15.38 % (CS/ALG-RNPP) and 16.63 % (CS/ALG-RCPP) at the specified ratios. The electrostatic association between CS and ALG was corroborated by zeta potential and near infrared analysis. 13C NMR analysis verified successful RPPs loading, with CS/ALG-RNPP displaying superior stability. Pharmacokinetics showed that both nanoparticles were sustained release and transported irregularly (0.43 < n < 0.85). Compared with the control group, CS/ALG-RPPs exhibited significantly increased glucose tolerance, serum GLP-1 (Glucagon-like peptide 1) content, and CaSR expression which play pivotal roles in glucose homeostasis (*p < 0.05). These findings proposed that CS/ALG-RPPs hold promise in achieving sustained release within the intestinal epithelium, thereby augmenting the therapeutic efficacy of targeted peptides.


Assuntos
Brassica napus , Quitosana , Nanopartículas , Humanos , Quitosana/química , Portadores de Fármacos/química , Preparações de Ação Retardada , Brassica napus/metabolismo , Alginatos/química , Nanopartículas/química , Glucose , Peptídeos
5.
Naunyn Schmiedebergs Arch Pharmacol ; 397(8): 5387-5401, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38396154

RESUMO

Allelochemicals are secondary metabolites which function as a natural protection against grazing activities by algae and higher plants. They are one of the major metabolites engaged in the interactions of organisms. The chemically mediated interactions between organisms significantly influence the functioning of the ecosystems. Most of these compounds are secondary metabolites comprising sterols, terpenes, and polyphenols. These compounds not only play a defensive role, but also exhibit biological activities such as antioxidants, anti-cancer, anti-diabetes, anti-inflammation, and anti-microbial properties. This review article discusses the current understanding of the allelochemicals of seaweeds and their bioprospecting potential that can bring benefit to humanity. Specifically, the bioactive substances having specific health benefits associated with the consumption or application of seaweed-derived compounds. The properties of such allelochemicals can have implications for bioprospecting pharmaceutical, nutraceutical and cosmetic applications.


Assuntos
Bioprospecção , Feromônios , Alga Marinha , Alga Marinha/química , Humanos , Animais , Feromônios/química , Feromônios/isolamento & purificação , Feromônios/farmacologia , Bioprospecção/métodos
6.
Molecules ; 28(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37959693

RESUMO

Ligustrum robustum has been not only used as a heat-clearing and detoxicating functional tea (Ku-Ding-Cha) but also consumed as a hypotensive, anti-diabetic, and weight-reducing folk medicine. From the leaves of L. robustum, ten new monoterpenoid glycosides named ligurobustosides T10 (1a), T11 (1b), T12 (2a), T13 (2b), T14 (3a), T15 (3b), F1 (4b), T16 (5a), T17 (5b), and E1 (6b), together with five known ones (4a, 6a, 7, 8a, 8b), were separated and identified using the spectroscopic method and chemical method in this research. The results of biological tests exhibited that the fatty acid synthase (FAS) inhibitory action of compound 5 (IC50: 4.38 ± 0.11 µM) was as strong as orlistat (IC50: 4.46 ± 0.13 µM), a positive control; the α-glucosidase inhibitory actions of compounds 1-4 and 7-8, and the α-amylase inhibitory actions of compounds 1-8 were medium; the ABTS radical scavenging capacities of compounds 1-3 and 5-8 (IC50: 6.27 ± 0.23 ~ 8.59 ± 0.09 µM) were stronger than l-(+)-ascorbic acid (IC50: 10.06 ± 0.19 µM) served as a positive control. This research offered a theoretical foundation for the leaves of L. robustum to prevent diabetes and its complications.


Assuntos
Ligustrum , Ligustrum/química , Glicosídeos/farmacologia , Glicosídeos/química
7.
Saudi Pharm J ; 31(11): 101776, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37868645

RESUMO

Chronic diabetes mellites related hyperglycemia is a major cause of mortality and morbidity due to further complications like retinopathy, hypertension and cardiovascular diseases. Though several synthetic anti-diabetes drugs specifically targeting glucose-metabolism enzymes are available, they have their own limitations, including adverse side-effects. Unlike other natural or marine-derived pharmacologically important molecules, deep-sea fungi metabolites still remain under-explored for their anti-diabetes potential. We performed structure-based virtual screening of deep-sea fungal compounds selected by their physiochemical properties, targeting crucial enzymes viz., α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B involved in glucose-metabolism pathway. Following molecular docking scores and MD simulation analyses, the selected top ten compounds for each enzyme, were subjected to pharmacokinetics prediction based on their AdmetSAR- and pharmacophore-based features. Of these, cladosporol C, tenellone F, ozazino-cyclo-(2,3-dihydroxyl-trp-tyr), penicillactam and circumdatin G were identified as potential inhibitors of α -amylase, α -glucosidase, pancreatic-lipoprotein lipase, hexokinase-II and protein tyrosine phosphatase-1B, respectively. Our in silico data therefore, warrants further experimental and pharmacological studies to validate their anti-diabetes therapeutic potential.

8.
Heliyon ; 9(10): e20808, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37860571

RESUMO

This study evaluated the anti-diabetic effect of polysaccharides isolated from Ornithogalum caudatum and their underlying mechanisms. To achieve this, a type 2 diabetes mellitus mouse model was established using a combination of a high-fat diet and low-dose streptozotocin injection. The mice were treated with Ornithogalumcaudatum polysaccharides (OCPs) for 4 weeks. OCPs treatment significantly decreased body weight loss, fasting blood glucose levels, and plasma insulin levels in diabetic mice. Additionally, compared with the untreated group, OCPs treatment significantly decreased total cholesterol, triacylglycerol, and low-density lipoprotein-cholesterol levels, but increased those of high-density lipoprotein-cholesterol in diabetic mice. Moreover, antioxidant enzyme activity and histopathology results revealed that OCPs effectively alleviated oxidative stress and streptozotocin-induced lesions by increasing antioxidant enzyme activity. Results from mechanistic studies showed that OCPs treatment significantly increased the expression of p-PI3K, p-Akt, and p-GSK-3ß in the liver. Moreover, OCPs optimized the gut microbiota composition of diabetic mice by significantly decreasing the Firmicutes/Bacteroidetes ratio and increasing the levels of beneficial bacteria (Muribaculaceae_norank, Prevotellaceae_UCG-001 and Alloprevotella). Overall, these findings suggest that OCPs exert anti-diabetic effects by triggering the PI3K/Akt/GSK-3ß signaling pathway and regulating the gut microbiota.

9.
Chem Biol Drug Des ; 102(6): 1643-1657, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37705131

RESUMO

Ursolic acid (UA) is a pentacyclic triterpenoid, which exhibits many biological activities, particularly in anti-cardiovascular and anti-diabetes. The further application of UA is greatly limited due to its low bioavailability and poor water solubility. Up to date, various UA derivatives have been designed to overcome these shortcomings. In this paper, the authors reviewed the development of UA derivatives as the anti-diabetes anti-cardiovascular reagents.


Assuntos
Triterpenos , Solubilidade , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Ácido Ursólico
10.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37631052

RESUMO

This study presents a phytochemical investigation of Lepionurus sylvestris leaf extracts and their anti-diabetic activities. Traditionally, L. sylvestris leaves were used as vegetables and food in local recipes, but the root extracts of the plant can also be used in body tonic and erectile dysfunction treatments. Following a preliminary anti-diabetic activity screening test, the 80% ethanolic leaf extract exhibited potent anti-alpha glucosidase activity. So, the leaves' active components were selected for further investigation. Firstly, the plant was extracted via maceration using lower to higher polarity solvents such as hexane, ethyl acetate, ethanol, and water, respectively, to obtain the four crude extracts. Then, the phytochemicals contained in this plant were investigated via classical column chromatography and spectroscopy techniques. Anti-diabetic activity was evaluated via anti-alpha glucosidase and insulin secretagogue assays. The results showed that five compounds were isolated from the fractionated ethanolic leaf extract: interruptin A; interruptin C; ergosterol; diglycerol; and 15-16-epoxy-neo-cleoda-3,7(20),13(16),14-tetraene-12,17:18,19-diolide, a new diterpene derivative which is herein referred to as lepionurodiolide. Interruptin A and the new diterpene derivative exhibited the greatest effect on anti-alpha glucosidase activity, showing IC50 values of 293.05 and 203.71 µg/mL, respectively. Then, molecular docking was used to study the sites of action of these compounds. The results showed that interruptin A and the new compound interacted through H-bonds with the GLN279 residue, with a binding energy of -9.8 kcal/mol, whereas interruptin A and C interacted with HIS280 and ARG315 a with binding energy of -10.2 kcal/mol. Moreover, the extracts were investigated for their toxicity toward human cancer cells, and a zebrafish embryonic toxicity model was used to determine herbal drug safety. The results indicated that ethyl acetate and hexane extracts showed cytotoxicity to both Hela cells and human breast adenocarcinomas (MCF-7), which was related to the results derived from using the zebrafish embryonic toxicity model. The hexane and ethyl acetate presented LC50 values of 33.25 and 36.55 µg/mL, respectively, whereas the ethanol and water extracts did not show embryonic toxicity. This study is the first of its kind to report on the chemical constituents and anti-diabetic activity of L. sylvestris, the leaf extract of which has been traditionally used in southern Thailand as a herbal medicine and food ingredient.

11.
Phytochemistry ; 213: 113769, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37343738

RESUMO

Four undescribed compounds (two 1,5-anhydro-d-glucitol derivatives and two galloyl derivatives) and fourteen known compounds were isolated and structurally identified from leaves of Acer ginnala Maxim. (Amur maple). Structures and absolute configurations of the four undescribed compounds were determined using extensive analysis of NMR spectroscopic, HRESI-MS, modified Mosher ester method, and comparison with spectroscopic data of known compounds. Bioactivity evaluation revealed that the isolated 1,5-anhydro-d-glucitol derivative, galloylated flavonol rhamnosides, and galloylated flavanols had inhibitory effects on both protein tyrosine phosphatase-1B (PTP1B, IC50 values ranging of 3.46-12.65 µM) and α-glucosidase (IC50 values ranging of 0.88-6.06 µM) in comparison with a positive control for PTP1B (ursolic acid, IC50 = 5.10 µM) or α-glucosidase (acarbose, IC50 = 141.62 µM). A combination of enzyme kinetic analysis and molecular docking provided additional evidence in favor of their inhibitory activities and mechanism. These data demonstrate that A. ginnala Maxim. together with its constituents are promising sources of potent candidates for developing novel anti-diabetic medications.


Assuntos
Acer , Inibidores Enzimáticos , Inibidores Enzimáticos/química , alfa-Glucosidases/metabolismo , Acer/química , Acer/metabolismo , Flavonoides/metabolismo , Sorbitol/química , Sorbitol/farmacologia , Simulação de Acoplamento Molecular , Cinética , Folhas de Planta/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1
12.
Int J Biol Macromol ; 242(Pt 2): 124713, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148946

RESUMO

The chitosan matrix was used as a substrate for ZnO nanoflowers (ZnO/CH) and Ce-doped ZnO nanoflowers (Ce-ZnO/CH) by microwave-induced hydrothermal synthesis processes. The obtained hybrid structures were assessed as enhanced antioxidant and antidiabetic agents considering the synergetic effect of the different components. The integration of chitosan and cerium induced significantly the biological activity of ZnO flower-like particles. Ce-doped ZnO nano-flowers show higher activities than both ZnO nanoflowers and ZnO/CH composite reflecting the strong effect of surface electrons that were formed by the doping process as compared to the high interactive interface of the chitosan substrate. As an antioxidant the synthetic Ce-ZnO/CH composite achieved remarkable scavenging efficiencies for DPPH (92.4 ± 1.33 %), nitric oxide (95.2 ± 1.81 %), ABTS (90.4 ± 1.64 %), and superoxide (52.8 ± 1.22 %) radicals which are significantly higher values than Ascorbic acid as standard and the commercially used ZnO nanoparticles. Also, its antidiabetic efficiency enhanced greatly achieving strong inhibition effects on porcine α-amylase (93.6 ± 1.66 %), crude α-amylase (88.7 ± 1.82 %), pancreatic α-glucosidase (98.7 ± 1.26 %), crude intestinal α-glucosidase (96.8 ± 1.16 %), and amyloglucosidase (97.2 ± 1.72 %) enzymes. The recognized inhibition percentages are notably higher than the determined percentages using miglitol drug and slightly higher than acarbose. This recommends the Ce-ZnO/CH composite as a potential antidiabetic and antioxidant agent compared with the high cost and the reported side effects of the commonly used chemical drug.


Assuntos
Quitosana , Óxido de Zinco , Animais , Suínos , Antioxidantes/farmacologia , Quitosana/química , Óxido de Zinco/química , alfa-Glucosidases , Micro-Ondas , Hipoglicemiantes/farmacologia , alfa-Amilases
13.
Int J Biol Macromol ; 240: 124301, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37004936

RESUMO

To fully research the anti-diabetic activity of apricot polysaccharide, low temperature plasma (LTP) was used to modify apricot polysaccharide. The modified polysaccharide was isolated and purified using column chromatography. It was found that LTP modification can significantly improve the α-glucosidase glucosidase inhibition rate of apricot polysaccharides. The isolated fraction FAPP-2D with HG domain showed excellent anti-diabetic activity in insulin resistance model in L6 cell. We found that FAPP-2D increased the ADP/ATP ratio and inhibited PKA phosphorylation, activating the LKB1-AMPK pathway. Moreover, FAPP-2D activated AMPK-PGC1α pathway, which could stimulated mitochondrial production and regulate energy metabolism, promoting GLUT4 protein transport to achieve an anti-diabetic effect. The Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy data showed that the LTP modification could increase the CH bond content while decreasing the C-O-C/C-O bond content, indicating that LTP destroyed the C-O-C/C-O bond, which enhanced the anti-diabetes activity of the modified apricot pectin polysaccharide. Our findings could pave the way for the molecular exploitation of apricot polysaccharides and the application of low-temperature plasma.


Assuntos
Diabetes Mellitus , Prunus armeniaca , Pectinas/química , Prunus armeniaca/química , Temperatura , Proteínas Quinases Ativadas por AMP/metabolismo , Polissacarídeos/química
14.
Intern Emerg Med ; 18(4): 1049-1063, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36964858

RESUMO

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Idoso , Humanos , Estudos Transversais , Hospitalização , Prescrições de Medicamentos
15.
Int J Mol Sci ; 24(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36902218

RESUMO

Type-2 Diabetes Mellitus is a complex, chronic illness characterized by persistent high blood glucose levels. Patients can be prescribed anti-diabetes drugs as single agents or in combination depending on the severity of their condition. Metformin and empagliflozin are two commonly prescribed anti-diabetes drugs which reduce hyperglycemia, however their direct effects on macrophage inflammatory responses alone or in combination are unreported. Here, we show that metformin and empagliflozin elicit proinflammatory responses on mouse bone-marrow-derived macrophages with single agent challenge, which are modulated when added in combination. In silico docking experiments suggested that empagliflozin can interact with both TLR2 and DECTIN1 receptors, and we observed that both empagliflozin and metformin increase expression of Tlr2 and Clec7a. Thus, findings from this study suggest that metformin and empagliflozin as single agents or in combination can directly modulate inflammatory gene expression in macrophages and upregulate the expression of their receptors.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Macrófagos , Metformina , Animais , Camundongos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Expressão Gênica/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Receptor 2 Toll-Like/uso terapêutico
16.
BMC Complement Med Ther ; 23(1): 83, 2023 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934269

RESUMO

BACKGROUND: Increased glucose level and insulin resistance are major factors in Type 2 diabetes mellitus (T2M), which is chronic and debilitating disease worldwide. Submerged culture medium of Ceriporia lacerata mycelium (CLM) is known to have glucose lowering effects and improving insulin resistance in a mouse model in our previous studies. The main purpose of this clinical trial was to evaluate the functional efficacy and safety of CLM in enrolled participants with impaired fasting blood sugar or mild T2D for 12 weeks. METHODS: A total of 72 participants with impaired fasting blood sugar or mild T2D were participated in a randomized, double-blind, placebo-controlled clinical trial. All participants were randomly assigned into the CLM group or placebo group. Fasting blood glucose (FBG), HbA1c, insulin, C-peptide, HOMA-IR, and HOMA-IR by C-peptide were used to assess the anti-diabetic efficacy of CLM for 12 weeks. RESULTS: In this study, the effectiveness of CLM on lowering the anti-diabetic indicators (C-peptide levels, insulin, and FBG) was confirmed. CLM significantly elicited anti-diabetic effects after 12 weeks of ingestion without showing any side effects in both groups of participants. After the CLM treatment, FBG levels were effectively dropped by 63.9% (ITT), while HOMA-IR level in the CLM group with FBG > 110 mg/dL showed a marked decrease by 34% up to 12 weeks. Remarkably, the effect of improving insulin resistance was significantly increased in the subgroup of participants with insulin resistance, exhibiting effective reduction at 6 weeks (42.5%) and 12 weeks (61%), without observing a recurrence or hypoglycemia. HbA1c levels were also decreased by 50% in the participants with reduced indicators (FBG, insulin, C-peptide, HOMA-IR, and HOMA-IR). Additionally, it is noteworthy that the levels of insulin and C-peptide were significantly reduced despite the CLM group with FBG > 110 mg/dL. No significant differences were detected in the other parameters (lipids, blood tests, and blood pressure) after 12 weeks. CONCLUSION: The submerged culture medium of CLM showed clinical efficacy in the improvement of FBG, insulin, C-peptide, HbAc1, and HOMA-index. The microbiome-based medium could benefit patients with T2D, FBG disorders, or pre-diabetes, which could guide a new therapeutic pathway in surging the global diabetes epidemic.


Assuntos
Meios de Cultura , Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Resistência à Insulina , Polyporales , Glicemia , Peptídeo C , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Insulina , Humanos , Meios de Cultura/farmacologia , Hipoglicemiantes/farmacologia
17.
Healthcare (Basel) ; 11(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36833075

RESUMO

This study aimed to examine the difference in health-related quality of life (HRQOL) and diabetes-related healthcare events (HCEs) among adults with diabetes who were on metformin, sulfonylurea, insulin, or thiazolidinedione (TZD) monotherapy. The data were sourced from the Medical Expenditure Panel Survey (MEPS). Diabetes patients ≥18 years old who had a complete record of physical component score and mental component scores in round 2 and round 4 of the survey were included. The primary outcome was HRQOL of diabetes patients as measured by the Medical Outcome Study short-form (SF-12v2TM). Multinomial logistic regression and negative binomial regression were conducted to determine associated factors of HRQOL and HCE, respectively. Overall, 5387 patients were included for analysis. Nearly 60% of patients had unchanged HRQOL after the follow-up, whereas almost 15% to 20% of patients showed improvement in HRQOL. The relative risk of declined mental HRQOL was 1.5 times higher relative to unchanged mental HRQOL in patients who were on sulfonylurea 1.55 [1.1-2.17, p = 0.01] than metformin users. The rate of HCE decreased by a factor of 0.79, [95% CI: 0.63-0.99] in patients with no history of hypertension. Patients on sulfonylurea 1.53 [1.20-1.95, <0.01], insulin 2.00 [1.55-2.70, <0.01], and TZD 1.78 [1.23-2.58, <0.01] had increased risk of HCE compared to patients who were on metformin. In general, antidiabetic medications modestly improved HRQOL in patients with diabetes during the follow-up period. Metformin had a lower rate of HCE as compared to other medications. The selection of anti-diabetes medications should focus on HRQOL in addition to controlling glucose level.

18.
Gels ; 9(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36661827

RESUMO

(1) Background: This study attempted to develop an elder-friendly food suitable to the Korean Industrial Standard (KS) after identifying the nutritional characteristics of Kaniwa; (2) Methods: The nutrient composition and physiological activity of Kaniwa were analyzed, and the concentration of the gelling agent (guar gum, locust bean gum, and xanthan gum) to be added to Kaniwa mousse was derived through regression analysis to suit KS hardness level 1 to 3; (3) Results: It was found that Kaniwa not only had a good fatty acid composition but also had good antioxidant and anti-diabetic properties. Moreover, it was found that in order to have the hardness to chew Kaniwa mousse with the tongue, it was necessary to add less than 1.97% guar gum, 4.03% locust bean gum, and 8.59% xanthan gum. In order to have a hardness that can be chewed with the gum, it was found that 2.17~4.97% guar gum, 4.45~10.28% locust bean gum, and 9.48~21.96% xanthan gum should be added; (4) Conclusions: As the aging rate and life expectancy increase, support for developmental research related to the elder-friendly industry should be continuously expanded in preparation for the upcoming super-aging society.

19.
Crit Rev Biotechnol ; 43(2): 242-257, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35156475

RESUMO

Diabetes is a chronic metabolic disease caused by insufficient insulin secretion and insulin resistance. Natural product is one of the most important resources for anti-diabetic drug. However, due to the extremely complex composition, this research is facing great challenges. After the advent of ligand fishing technology based on enzyme immobilization, the efficiency of screening anti-diabetic components has been greatly improved. In order to provide critical knowledge for future research in this field, the application progress of immobilized enzyme in screening anti-diabetic components from complex natural extracts in recent years was reviewed comprehensively, including novel preparation technologies and strategies of immobilized enzyme and its outstanding application prospect in many aspects. The basic principles and preparation steps of immobilized enzyme were briefly described, including entrapment, physical adsorption, covalent binding, affinity immobilization, multienzyme system and carrier-free immobilization. New formatted immobilized enzymes with different carriers, hollow fibers, magnetic materials, microreactors, metal organic frameworks, etc., were widely used to screen anti-diabetic compositions from various natural products, such as Ginkgo biloba, Morus alba, lotus leaves, Pueraria lobata, Prunella vulgaris, and Magnolia cortex. Furthermore, the challenges and future prospects in this field were put forward in this review.


Assuntos
Produtos Biológicos , Diabetes Mellitus , Humanos , Produtos Biológicos/química , Enzimas Imobilizadas/química , Ligantes
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984554

RESUMO

Bavachinin is a dihydroflavone isolated from dried ripe fruits of Psoralea corylifolia L.,which has various pharmacological activities, such as anti-tumor, anti-virus, anti-diabetes, anti-inflammatory and neuroprotective, and good potential in clinical applications. With the increasing concern about the safety of P. corylifolia applications in clinical, the bavachinin has been found to be one of the main components causing liver injury. In this paper, the pharmacological activities and hepatotoxicity of bavachinin in the recent 20 years were reviewed, in order to provide reference for the further study and clinical application.

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