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1.
Braz. j. biol ; 84: e254234, 2024. tab, graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1364499

RESUMO

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.


Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.


Assuntos
Ratos , Modelos Animais , Diabetes Mellitus , Desenvolvimento de Medicamentos , Hipoglicemiantes , Antioxidantes
2.
Food Chem ; 403: 134336, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36191423

RESUMO

Konjac glucomannan's influence on the regulation of diabetes mellitus, hyperlipidemia, and gut microbial flora was evaluated in this study. In addition, a high-fat diet and streptozotocin were used to induce type 2 diabetes mellitus in rats. At the end of the study, we analyzed various parameters such as body weight, plasma lipid profile, insulin levels by immunohistochemistry, degree of fibrosis in the liver, protein expression of PPAR-γ and p-SREBP-1C and gut microbial changes using 16S rRNA sequencing. The results of our study suggest that KGM supplementation significantly reduced the plasma lipid profile (TC, TG, VLDL, LDL, etc.). In addition, KGM has improved insulin levels, which were visualized using immunohistochemistry. Furthermore, KGM also regulated the protein expression of key regulatory proteins of lipid metabolism PPAR-γ and p-SREBP-1C (Group 3). Similar results were seen in the groups treated with the standard drug rosiglitazone (group 4). Finally, the 16S rRNA sequencing shows that KGM contributes to gut microbiota composition alterations, and it was observed using the Simpson, Shannon, Chao-1, and actual otus indices (group 3). KGM further alters the production of beneficial SCFAs and helps host good health. Furthermore, several metabolic pathways have been activated in T2DM rats. As a result, it becomes apparent that the digestive system's microbiome will play a role in T2DM. KGM has various health advantages but is particularly useful in treating hyperlipidemia and diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hiperlipidemias , Insulinas , Ratos , Animais , PPAR gama/genética , RNA Ribossômico 16S/genética , Hipoglicemiantes/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Fibras na Dieta/farmacologia , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Insulinas/farmacologia , Insulinas/uso terapêutico , Lipídeos/farmacologia
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121806, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36108405

RESUMO

Curcumin (bis-α,ß-unsaturated ß-diketone) plays an important role in the prevention of numerous diseases, including diabetes. Curcumin, as an enzyme inhibitor, has ideal structural properties including hydrophobic nature, flexible backbone, and several available hydrogen bond (H-bond) donors and acceptors. In this study, curcumin-fused aldohexose derivatives 3(a-c) were synthesized and used as influential agents in the treatment of diabetes with inhibitory properties against two carbohydrate-hydrolyzing enzymes α-glucosidase (α-Gls) and α-amylase (α-Amy) which are known to be significant therapeutic targets for the reduction of postprandial hyperglycemia. These compounds were isolated, purified, and then spectrally characterized via FT-IR, Mass, 1H, and 13C NMR, which strongly confirmed the targeted product's formation. Also, their inhibitory properties against α-Gls and α-Amy were evaluated spectroscopically. The Results indicated that all compounds strongly inhibited α-Amy and α-Gls by mixed and competitive mechanisms, respectively. The intrinsic fluorescence of α-Amy was quenched by the interaction with compounds 1 and 3b through a dynamic quenching mechanism, and the 1 and 3b/α-Amy complexes were spontaneously formed, mainly driven by the hydrophobic interaction and hydrogen bonding. Fourier transform infrared spectra (FT-IR) comprehensively verified that the binding of compounds 1 and 3b to α-Amy would change the conformation and microenvironment of α-Amy, thereby inhibiting the enzyme activity. Docking and molecular dynamics (MD) simulations showed that all compounds interacted with amino acid residues located in the active pocket site of the proteins. In vivo studies confirmed the plasma glucose diminution after the administration of compound 3b to Wistar rats. Accordingly, the results of the current work may prompt the scientific communities to investigate the possibility of compound 3b application in the clinic.


Assuntos
Curcumina , Diabetes Mellitus , Ratos , Animais , Hipoglicemiantes/química , Curcumina/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Ratos Wistar , alfa-Glucosidases/metabolismo , alfa-Amilases/metabolismo , Simulação de Acoplamento Molecular , Inibidores de Glicosídeo Hidrolases/química
4.
Methods Mol Biol ; 2576: 145-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36152183

RESUMO

Peroxisome proliferator-activated receptors (PPARs) have been exploited as drug targets for combating multiple diseases. Several activators with different selectivity for the PPAR α, γ, and δ subtypes have been introduced into the market or have reached advanced clinical trials. Binding assays are of utmost importance for the discovery and profiling of such PPAR ligands. Binding assays are often based on radioligands, in particular, tritiated molecules are applied. We developed synthetic procedures for tritiating various PPAR agonists and applied these radioligands for setting up a scintillation proximity assay (SPA) for PPAR α, γ, and δ. These SPAs allow to assess the binding affinities of PPAR α, γ, and δ ligands, along with their respective subtype selectivity profiles. Therefore, SPA is an important tool for hit discovery and lead optimization campaigns aimed at identifying next-generation PPAR ligands.


Assuntos
PPAR alfa , PPAR delta , Hipoglicemiantes , Ligantes , PPAR alfa/agonistas , PPAR alfa/metabolismo , PPAR delta/agonistas , PPAR delta/metabolismo , PPAR gama/metabolismo , Receptores Ativados por Proliferador de Peroxissomo
5.
Food Chem ; 399: 133974, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35998493

RESUMO

In this research, two sequential Dendrobium officinale water extracts (WDOE and WDOP1) were shown to significantly ameliorate type 2 diabetic mellitus (T2DM) in a mouse model. WDOP1 was identified as a glucomannan with a backbone of 1,4-linked Manp and 1,4-linked Glcp and an average molecular weight of 731 kDa. We also found that both WDOE and WDOP1 could significantly alleviate glucose intolerance, insulin resistance, oxidative stress injury, serum lipid metabolism disturbances, and histopathological damage in T2DM mice. In addition, we demonstrated that WDOE and WDOP1 reversed gut dysbiosis by reshaping the microbiota spectrum in T2DM mice. It should be emphasized that both Dendrobium officinale extracts afforded beneficial effects in T2DM mice comparable to metformin, despite differences in examined dosages. In conclusion, we demonstrated that Dendrobium officinale derivatives have potential as T2DM management nutraceuticals.


Assuntos
Dendrobium , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Camundongos , Estresse Oxidativo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia
6.
J Ethnopharmacol ; 300: 115750, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36162547

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Different Physalis plants have been widely employed in traditional medicine for management of diabetes mellitus. Previous studies with respect to the in vivo antidiabetic activity of Physalis plants illustrated that they improved glucose and lipid metabolism in streptozotocin (STZ) -induced diabetic rats yet the mechanism of action of bioactive constituents of the different organs of Physalis plants on diabetes remains obscure. AIM OF STUDY: Our objective is to study the effects of the different organs of ground cherry (P. pruinosa) on diabetes in rat models and elucidate their mechanism of actions through serum pharmacochemistry combined to network pharmacology analyses and in-vivo testing. MATERIALS AND METHODS: Characterization of the constituents in the drug-dosed serum samples relative to the blank serum after treatment with different extracts was performed by UPLC -MS/MS technique. The absorbed metabolites where then subjected to network pharmacology analysis to construct an interaction network linking "compound-target-pathway". In vivo verification was implemented to determine a hypothesized mechanism of action on a STZ and high fat diet induced type II diabetes mellitus (T2DM) model based on functional and enrichment analyses of the Kyoto Encyclopedia of Genes and Genome and Gene Ontology. RESULTS: Identification of a total of 73 compounds (22 prototypes and 51 metabolites) derived from P. pruinosa extracts was achieved through comparison of the serum samples collected from diabetic control group and extracts treated groups. The identified compounds were found to belong to different classes according to their structural type including withanolides, physalins and flavonoids. The absorbed compounds in the analyzed serum samples were considered as the potential bioactive components. The component-target network was found to have 23 nodes with 17 target genes including MAPK8, CYP1A1 and CYP1B1. Quercetin and withaferin A were found to possess the highest combined score in the C-T network. Integrated serum pharmacochemistry and network pharmacology analyses revealed the enrichment of leaves extract with the active constituents, which can be utilized in T2DM treatment. In the top KEGG pathways, lipid and atherosclerosis metabolic pathways in addition to T2DM pathways were found to be highly prioritized. The diabetic rats, which received leaves extract exhibited a substantial increment in GLUT2, INSR, IRS-1, PI3K-p85 and AKT-ser473 proteins by 105%, 142%, 109%, 81% and 73%, respectively relative to the untreated diabetic group. The immunoblotting performed for MAPK and ERK1/2 part of the inflammatory pathway studied in STZ induced diabetic rats revealed that leaves, calyces and stems extracts resulted in a substantial diminish in p38-MAPK, ERK 1/2, NF-κB, and TNF-α. Histopathological examination revealed that the hepatic histoarchitecture was substantially improved in the leaves, stems, and clayces-treated rats in comparison with untreated diabetic rats. Further, pancreatic injuries, which induced by STZ were dramatically altered by the treatment with P. pruinosa leaves, calyces and stems extracts. ß-cells in diabetic rats received leaves extract disclosed moderate insulin immunostaining with a notable increase in the mean insulin area%. CONCLUSIONS: The study in hand offers a comprehensive study to clarify the bioactive metabolites of the different organs of P. pruinosa. The basic pharmacological effects and underlying mechanism of actions in the management of STZ and high fat diet induced T2DM were specifically covered in this paper.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Physalis , Vitanolídeos , Animais , Citocromo P-450 CYP1A1 , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , NF-kappa B , Farmacologia em Rede , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/uso terapêutico , Ratos , Estreptozocina , Espectrometria de Massas em Tandem , Fator de Necrose Tumoral alfa
7.
J Ethnopharmacol ; 300: 115752, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36174807

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Peganum harmala L. is a traditional medicinal plant used for centuries in folk medicine. It has a wide array of therapeutic attributes, which include hypoglycemic, sedative, anti-inflammatory, and antioxidant properties. The fruit decoction of this plant was claimed by Avicenna as traditional therapy for urolithiasis. Also, P. harmala seed showed a clinical reduction in kidney stone number and size in patients with urolithiasis. AIM OF THE STUDY: In light of the above-mentioned data, the anti-urolithiatic activities of the seed extracts and the major ß-carboline alkaloids of P. harmala were investigated. MATERIALS AND METHODS: Extraction, isolation, and characterization of the major alkaloids were performed using different chromatographic and spectral techniques. The in vivo anti-urolithiatic action was evaluated using ethylene glycol (EG)-induced urolithiasis in rats by studying their mitigating effects on the antioxidant machinery, serum toxicity markers (i.e. nitrogenous waste, such as blood urea nitrogen, uric acid, urea, and creatinine), minerals (such as Ca, Mg, P, and oxalate), kidney injury marker 1 (KIM-1), and urinary markers (i.e. urine pH and urine output). RESULTS: Two major alkaloids, harmine (P1) and harmalacidine HCl (P2), were isolated and in vivo evaluated alongside the different extracts. The results showed that P. harmala and its constituents/fractions significantly reduced oxidative stress at 50 mg/kg body weight, p.o., as demonstrated by increased levels of glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), and catalase (CAT) in kidney homogenate as compared to the EG-treated group. Likewise, the total extract, pet. ether fraction, n-butanol fraction, and P1, P2 alleviated malondialdehyde (MDA) as compared to the EG-treated group. Serum toxicity markers like blood urea nitrogen (BUN), creatinine, uric acid, urea, kidney injury molecule-1 (Kim-1), calcium, magnesium, phosphate, and oxalate levels were decreased by total extract, pet. ether fraction, n-butanol fraction, P1, and P2 as compared to the EG-treated group. Inflammatory markers like NFκ-B and TNF-α were also downregulated in the kidney homogenate of treatment groups as compared to the EG-treated group. Moreover, urine output and urine pH were significantly increased in treatment groups as compared to the EG-treated group deciphering anti-urolithiatic property of P. harmala. Histopathological assessment by different staining patterns also supported the previous findings and indicated that treatment with P. harmala caused a gradual recovery in damaged glomeruli, medulla, interstitial spaces and tubules, and brown calculi materials as compared to the EG-treated group. CONCLUSION: The current research represents scientific evidence on the use of P. harmala and its major alkaloids as an effective therapy in the prevention and management of urolithiasis.


Assuntos
Alcaloides , Cálculos Renais , Peganum , Urolitíase , 1-Butanol , Alcaloides/farmacologia , Animais , Antioxidantes , Cálcio , Oxalato de Cálcio/urina , Catalase , Creatinina , Éteres , Etilenoglicol/uso terapêutico , Etilenoglicol/toxicidade , Glutationa , Glutationa Peroxidase , Glutationa Redutase , Harmina , Hipnóticos e Sedativos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Cálculos Renais/tratamento farmacológico , Magnésio , Malondialdeído , Peganum/química , Fosfatos , Extratos Vegetais , Ratos , Fator de Necrose Tumoral alfa , Ureia , Ácido Úrico , Urolitíase/induzido quimicamente , Urolitíase/tratamento farmacológico , Urolitíase/patologia
8.
Food Chem ; 404(Pt A): 134598, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444040

RESUMO

Crude polysaccharides extracted from red kidney bean (RK) display significant antidiabetic activity in type 2 diabetic mice, but the underlying mechanism and the core functional component has not been elucidated. In this study, the antidiabetic effect and mechanism of RK are investigated by serum metabolomics and high-throughput sequencing. In addition, the key component was identified by evaluating the improvement on glucose and lipid homeostasis in type 2 diabetic rats. Our data indicated that RK relieved the symptoms of hyperglycemia, hyperlipidemia in STZ-induced diabetic rats. RK not only improved the metabolic disturbance by regulating the biosynthesis of unsaturated fatty acids, but also modified gut microbiota composition by selectively enriching in key genera of Bacteroides, Phascolarctobacterium, Succinivibrio, Blautia. We further found the purified polysaccharides (RKP) were identified as the core biofunctional component in RK. Our present studies provide evidence that RKP are potential effective dietary supplement for type 2 diabetic individuals.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hiperglicemia , Hiperlipidemias , Phaseolus , Ratos , Camundongos , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/genética , Polissacarídeos , Hipoglicemiantes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Lipídeos
9.
Food Chem ; 404(Pt B): 134735, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444094

RESUMO

Foxtail millet and its components have hypoglycemic effects on mice, but the role of starch and protein in millet in these effects is unclear. The present study investigated the impact of heat-treated foxtail millet starch and protein on type 2 diabetic mice and the underlying mechanisms, including the influence of gut microbiota and serum metabolic profile. In diabetic mice, the consumption of heat-treated foxtail millet starch and protein reduced, respectively, fasting blood glucose 18.52% and 26.33% and insulin levels 12.22% and 15.96%. In addition, heat-treated foxtail millet starch and protein altered the gut microbiota composition, enriched the abundance of probiotics and short-chain fatty acids producing bacteria, reduced harmful bacteria, and increased fecal short-chain fatty acids concentration. Heat-treated foxtail millet protein had greater effects on gut microbiota composition, whereas heat-treated foxtail millet starch had greater effects on metabolic function. The hypoglycemic potential of heat-treated foxtail millet starch and protein was associated with the modulation of both gut microbiota and serum metabolic profile.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Setaria (Planta) , Camundongos , Animais , Setaria (Planta)/genética , Amido , Temperatura Alta , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes , Diabetes Mellitus Tipo 2/tratamento farmacológico
10.
Food Chem ; 404(Pt B): 134650, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36283320

RESUMO

Hylocereus spp. known as dragon fruit is an exotic fruit that belongs to the Cactaceae family. LC-QTOF-MS and multivariate statistical tools were established to analyze differences in the composition of dragon fruit peel and pulp from Egypt, Germany, Philippines, and China. The α-glucosidase inhibitory effects of different extracts were carried out along with the anti-glycation end products (AGE) using BSA-fructose, BSA-methylglyoxal, and arginine-methylglyoxal assays. In addition, the total antioxidant capacity was investigated as a complementary mechanism to AGE formation. Principal component analysis revealed that dragon fruits from China and Egypt were the most distinct among all samples due to betalains content. Orthogonal projection to latent structures-discriminant analysis identified 16 compounds highly correlated to the antiglycation activity such as betanin, γ-aminobutyric acid, neobetanin, and portulacaxanthin II. Pulp extracts were more active than peels as inhibitors of α-glucosidase. While peels were more active as AGE formation inhibitors and as antioxidants.


Assuntos
Cactaceae , Hipoglicemiantes , Hipoglicemiantes/farmacologia , Hipoglicemiantes/metabolismo , alfa-Glucosidases/metabolismo , Aldeído Pirúvico/metabolismo , Quimiometria , Cactaceae/metabolismo , Frutas/química , Antioxidantes/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo
11.
Environ Res ; 216(Pt 3): 114714, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334834

RESUMO

The nanoparticles based drug delivery and treatment related research has been increased significantly in the recent years. Hence, the antibacterial, antifungal, and antioxidant activity potential of pre synthesized and characterized Titanium dioxide nanoparticles (TiO2 NPs) were investigated in this study through respective standard protocols. Interestingly, the obtained results revealed that TiO2 NPs have concentration dependent antibacterial activity against bacterial pathogens such as E. coli, P.mirabilis, V. cholerae, P. aeruginosa, S. typhimurium, and S. aureus at 100 µg mL-1 concentration. Furthermore, these TiO2 NPs showed remarkable antifungal activity against aspergillosis causing fungal pathogens such as A. niger, A. fumigatus, A. nidulans, and A. flavus at 100 µg mL-1 concentration. α-glucosidase. This TiO2 NPs also effectively inhibit the α-amylase (17%) and α-Glucosidase (37%) enzyme activity at 100 µg mL-1 dosage. The DPPH assay revealed that TiO2 NPs effectively scavenge DPPH free radicals by up to 89% at 100 µg mL-1 concentration, which was comparable to butylated hydroxytoluene (96%). These results suggest that the plant-based TiO2 NPs have remarkable in-vitro antibacterial, antifungal, and antioxidant activity. These may be considered for additional in-vitro and in-vivo experiments to assess their potential biomedical applications.


Assuntos
Coleus , Nanopartículas Metálicas , Nanopartículas , Antifúngicos/farmacologia , Antifúngicos/química , Antioxidantes/farmacologia , Staphylococcus aureus , Escherichia coli , Hipoglicemiantes , alfa-Glucosidases , Titânio/química , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Pseudomonas aeruginosa , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química
12.
J Nutr Biochem ; 111: 109173, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228975

RESUMO

The antidiabetic effects of green tea have been demonstrated in clinical trials and epidemiological studies. This study investigated the antidiabetic effects of green tea extract (GTE) and its underlying molecular mechanisms using a leptin receptor-deficient db/db mouse model (Leprdb/db). Treatment with GTE for 2 weeks improved glucose tolerance and insulin sensitivity in Leprdb/db mice. In addition, GTE treatment reduced the body weight and adiposity of Leprdb/db mice. Furthermore, GTE treatment reduced pro-inflammatory gene expression, including nuclear factor kappa B (NF-κB) in white adipose tissue (WAT), and also reduced dipeptidyl peptidase-4 (DPP4) expression levels in WAT as well as in the serum. The promoter region of Dpp4 contains the NF-κB binding site, and DPP4 was found to be a direct target of NF-κB. Consistently, in vitro treatment of cells with GTE or its main constituent epigallocatechin gallate reduced lipopolysaccharide-induced NF-κB/DPP4 expression in 3T3-L1 adipocytes and RAW264.7 cells. Overall, our data demonstrated that GTE exerts an anti-diabetic effect by regulating the expression levels of NF-κB and DPP4 in WAT.


Assuntos
Dipeptidil Peptidase 4 , Hipoglicemiantes , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Tecido Adiposo/metabolismo , Chá/química
13.
Food Chem ; 404(Pt A): 134569, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36244070

RESUMO

In this study, a combined application of Polygonatum sibiricum saponin (PSS) with probiotics was developed as a new formulation that could be a candidate for a dietary supplement. The properties of nine probiotics were evaluated by principal component and heatmap analysis. And the hypoglycemic properties of compound probiotics were compared with single strains. The results showed the inhibition (%) of α-amylase was higher when L. casei ATCC393 was used synergistically with L. Bulgaricus 1.1480 compared with single strains as well as other strain combinations. And it was also found that the inhibition (%) of α-amylase was higher as 70.35 % after PSS and the compound probiotic were compounded as a ratio of 2:1. Furturemore, PSS-compound probiotics could regulate the composition of the gut microbiome of T2DM mice and enhance the metabolic capacity. In conclusion, the combination of PSS and compound probiotics has shown massive potential as management nutraceuticals of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Polygonatum , Probióticos , Saponinas , Camundongos , Animais , Hipoglicemiantes , Saponinas/farmacologia , alfa-Amilases
14.
J Ethnopharmacol ; 302(Pt A): 115899, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36336219

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum perforatum L., commonly known as St. John's Wort (SJW), represents one of the best-known and most thoroughly researched medicinal plant species. The ethnobotanical usage and bioactivities related to H. perforatum include treatment of skin diseases, wounds and burns, gastrointestinal problems, urogenital diseases and psychiatric disorders, particularly depression. In the last decade, many studies focused on the bioactive constituents responsible for the antihyperglycemic and antidiabetic activity of SJW extracts. However, the mechanism by which H. perforatum extract exhibits these properties is still unclear. Hence, the current study was designed to gain insight into the underlying biochemical and molecular mechanisms by which wildly growing H. perforatum exerts its antihyperglycemic and antidiabetic activities. MATERIAL AND METHODS: Plant material of H. perforatum was harvested from a natural population in the Republic of North Macedonia during full flowering season. Methanol (80% v/v) was used to extract bioactive components from HH powder. The dissolved HH dry extract (in 0.3% CMC) was given daily as a single treatment (200 mg/kg bw) during 14 days both in healthy and streptozotocin-induced diabetic rats. As a positive control, we applied glibenclamide. The activity of key enzymes involved in carbohydrate methabolisam in the liver were assessed, along with substrate concentration, as well as AMPK mRNA levels, PKCε concentration, plasma insulin level and pancreatic PARP activity. RESULTS: Compared to diabetic rats, treatment of diabetic rats with HH extract resulted with decreased activity of hepatic enzymes glucose-6-phospatase and fructose-1,6-bisphosphatase, increased liver glycogen and glucose-6-phosphate content, which resulted with reduced blood glucose concentration up to normoglycaemia. Non-significant changes were observed in the activity of hexokinase, glycogen phosphorylase and glucose-6-phospahte dehydrogenase. HH-treatment also caused an increase in plasma insulin concentration and increase in pancreatic PARP activity. Finally, HH treatment of diabetic rats showed significant increase in AMPK expression and decrease of PKCε concentration. CONCLUSION: We present in vivo evidence that HH- extract exert insulinotropic effects and regulate endogenous glucose production mostly by suppressing liver gluconeogenesis. The HH-treatment did not effected glycogenolysys and glycolysis. Finally, we confirm the antihyperglycemic and antidiabetic effect of HH-extract and the mechanism of this effect involves amelioration of AMPK and PKCε changes in the liver.


Assuntos
Diabetes Mellitus Experimental , Hypericum , Ratos , Animais , Hypericum/química , Proteínas Quinases Ativadas por AMP , Diabetes Mellitus Experimental/tratamento farmacológico , Gluconeogênese , Proteína Quinase C-épsilon , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Óleos Vegetais/uso terapêutico , Insulina , Glucose
15.
Eur J Med Chem ; 245(Pt 1): 114883, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36343410

RESUMO

Type 2 diabetes mellitus (T2DM) is a lifelong disease that requires long-term medication to control glucose levels, and thereby long-acting drug has been clinically needed for improving medical adherence. The free fatty acid receptor 1 (FFA1) was considered as a promising target for several diseases, such as T2DM, pain and fatty liver. However, no once-weekly FFA1 agonist has been reported until now. Herein, we report the successful discovery of ZLY50, the first once-weekly FFA1 agonist with a completely new chemotype, highly agonistic activity and selectivity on FFA1. Moreover, ZLY50 has enough brain exposure to activate FFA1 in brain, and it is the first orally available FFA1 agonist with analgesic activity. Notably, the long-term anti-diabetic and anti-fatty liver effects of ZLY50 (once-weekly) were better than those of HWL-088 (once-daily), a highly potent FFA1 agonist with far stronger glucose-lowering effect than Phase 3 clinical candidate TAK-875. Further mechanism studies suggested that ZLY50 alleviates fatty liver by regulating the expressions of genes related to lipid metabolism, mitochondrial function, and oxidative stress in liver.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Teste de Tolerância a Glucose , Ácidos Graxos não Esterificados/uso terapêutico , Receptores Acoplados a Proteínas G/agonistas , Glucose , Hipoglicemiantes/farmacologia
16.
Oncol Rep ; 49(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367180

RESUMO

Lung cancer is the most common type of cancer and the leading cause of cancer­associated death worldwide. Despite the availability of various treatments such as surgery, chemoradiotherapy, targeted drugs and immunotherapy, treatment is expensive and the prognosis remains poor. At present, lung cancer drugs and treatment programs remain in a state of continuous exploration and research to improve the prognosis, and to reduce the pain and economic burden for the patients. Type 2 diabetes is a common chronic disease in middle­aged and elderly patients, leading to significantly increased complications of cardiovascular and cerebrovascular diseases. Epidemiology shows that type 2 diabetes also increases the incidence of malignant tumors, including lung, liver, colorectal and pancreatic cancer. Metformin is a biguanide, widely used as a first­line oral drug in treating type 2 diabetes. Metformin has a hypoglycemic effect and a biological antitumor impact, reducing the incidence of various tumors, including lung cancer, and improving the prognosis of patients with tumors. The anti­lung cancer effect of metformin involves a variety of mechanisms that can improve the therapeutic effect and prognosis of lung cancer, as a single drug or in combination with other therapies. The present study aims to review the associated literature and the therapeutic effects of metformin on lung cancer.


Assuntos
Diabetes Mellitus Tipo 2 , Neoplasias Pulmonares , Metformina , Neoplasias Pancreáticas , Idoso , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/induzido quimicamente , Metformina/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico
17.
Chemosphere ; 311(Pt 1): 137066, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36328321

RESUMO

Bisphenol F (BPF) is a widely used bisphenol A (BPA) substitute plastic additive that has attracted increasing public concerns due to its potential toxic effects on animal and human health. Although previous studies have indicated that BPF might have harmful effects on metabolic homeostasis, the systematic effects of BPF on glucose disorders remain controversial. In this study, mice fed a normal chow diet (ND) and high-fat diet (HFD) were administered BPF at a dose of 100 µg/kg of body weight, and glucose metabolism was monitored after both short- and long-term treatment. Little change in glucose metabolism was observed in BPF-treated ND mice, but improved glucose metabolism was observed in BPF-treated HFD mice. Consistently, BPF treatment led to increased insulin signalling in the skeletal muscle of HFD mice. Additionally, liver metabolite levels also revealed increased carbohydrate digestion and improved TCA cycle progression in BPF-treated HFD mice. Our results demonstrate that sustained BPF exposure at an environmentally relevant dosage may substantially improve glucose metabolism and enhance insulin sensitivity in mice fed a high-fat diet.


Assuntos
Dieta Hiperlipídica , Hipoglicemiantes , Humanos , Camundongos , Animais , Compostos Benzidrílicos/farmacologia , Insulina/metabolismo , Glucose/metabolismo
18.
Bioorg Med Chem Lett ; 79: 129069, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36395995

RESUMO

In the present study, a series of cycloalkyl[b]thiophenylnicotinamide derivatives against α-glucosidase were synthesized, and evaluated for their in vitro and in vivo anti-diabetic potential. Most of the synthetic analogues exhibited superior α-glucosidase inhibitory effects than the standard drug acarbose (IC50 = 258.5 µM), in which compound 11b with cyclohexyl[b]thiophene core demonstrated the highest activity with an IC50 value of 9.9 µM and showed higher selectivity towards α-glucosidase over α-amylase by 7.4-fold. Fluorescence quenching experiment confirmed the direct binding of 11b with α-glucosidase, kinetics study revealed that 11b was a mixed-type inhibitor, and its binding mode was analyzed using molecular docking. Moreover, analogs compounds 6a-9b, 11b, 12b did not show in vitro cytotoxicity against LO2 and HepG2 cells. Finally, compound 11b exhibited in vivo hypoglycemic activity by reducing the blood glucose levels in sucrose-loaded rats.


Assuntos
Inibidores de Glicosídeo Hidrolases , alfa-Glucosidases , Animais , Ratos , Inibidores de Glicosídeo Hidrolases/farmacologia , Simulação de Acoplamento Molecular , Hipoglicemiantes/farmacologia , Acarbose
19.
PLoS One ; 17(12): e0278536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36455062

RESUMO

BACKGROUND: Poria cocos (Schw.) Wolf or Fuling is one of the top 10 most frequently prescribed herbs in China for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE: The purpose of this systematic review is to determine the additional benefit of Fuling formulae use in addition to hypoglycaemic agents for T2DM in randomised clinical trials. METHODS: English (5) and Chinese (4) medical databases were searched from their inception to August 2021. RCTs that included Fuling in herbal formulae for T2DM were included. Risk of bias were assessed using the Cochrane Collaboration's procedures. Stata software (13.0) was used for data analysis. RESULTS: Seventy-three RCTs (6,489 participants) with herbal formulae containing Fuling were included. Most studies were at risk of bias and strength of the evidence were low to moderate. Meta-analysis findings showed that the addition of formulae containing Fuling to hypoglycaemic agent-treatments could benefit people with T2DM by reducing fasting blood glucose (MD -0.82 [-0.93, -0.71]; I2 = 79.6%, P = 0.00), 2-hour postprandial blood glucose (MD-1.15 [-1.31, -0.98], I2 = 80%, P = 0.00) and haemoglobin A1c (MD-0.64 [-0.75, -0.53], I2 = 84.7%, P = 0.00). Adverse events were also significantly lower in the integrative group than in the hypoglycaemic alone group (RR 0.99 [0.93, 1.06], P = 0.87). CONCLUSION: Evidence from this study supports the use of Fuling formulae combined with hypoglycaemic agents for T2DM. The combined therapies appear to be well tolerated. TRAIL REGISTRATION: This review is registered with the PROSPERO international prospective register of systematic reviews (CRD42020214635).


Assuntos
Diabetes Mellitus Tipo 2 , Wolfiporia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia , Hipoglicemiantes/uso terapêutico , Hemoglobina A Glicada
20.
Diabetes Care ; 45(12): 2799-2805, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455118

RESUMO

Hypoglycemia remains a limiting factor in the optimal treatment of type 1 diabetes. Repeated episodes of hypoglycemia result in impaired awareness of subsequent hypoglycemic events, inducing a vicious feed-forward cycle and increasing the risk of morbidity and mortality. Why this occurs and how to manage the problem in clinical practice remain uncertain. To address the obstacles and barriers that have hindered progress in this clinically important area, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on 14-15 October 2021. This perspective offers a summary of this outstanding meeting, which brought clinical and basic scientists from the fields of diabetes, neuroscience, psychology, psychiatry, and imaging together, on how to best advance the field of impaired awareness of hypoglycemia and hypoglycemia in general in patients with diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Estados Unidos , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Digestão
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