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1.
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
2.
Oxid Med Cell Longev ; 2022: 2297268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120597

RESUMO

Objective: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) commonly coexist and act synergistically to drive adverse clinical outcomes. This study is aimed at investigating the effects of exercise intervention and oral hypoglycaemic drug of metformin (MET) alone or combined on hepatic lipid accumulation. To investigate if oxidative stress and endoplasmic reticulum stress (ERS) are involved in lipotoxicity-induced hepatocyte apoptosis in diabetic mice and whether exercise and/or MET alleviated oxidative stress or ERS-apoptosis by AMPK-Nrf2-HO-1 signaling pathway. Methods: Forty db/db mice with diabetes (random blood glucose ≥ 250 mg/dL) were randomly allocated into four groups: control (CON), exercise training alone (EX), metformin treatment alone (MET), and exercise combined with metformin (EM) groups. Hematoxylin-eosin and oil red O staining were carried out to observe hepatic lipid accumulation. Immunohistochemical and TUNEL methods were used to detect the protein expression of the binding immunoglobulin protein (BiP) and superoxide dismutase-1 (SOD1) and the apoptosis level of hepatocytes. ERS-related gene expression and the AMPK-Nrf2-HO-1 signaling pathway were tested by western blotting. Results: Our data showed that db/db mice exhibited increased liver lipid accumulation, which induced oxidative and ER stress of the PERK-eIF2α-ATF4 pathway, and hepatocyte apoptosis. MET combined with exercise training significantly alleviated hepatic lipid accumulation by suppressing BiP expression, the central regulator of ER homeostasis, and its downstream PERK-eIF2α-ATF4 pathway, as well as upregulated the AMPK-Nrf2-HO-1 signaling pathway. Moreover, the combination of exercise and MET displayed protective effects on hepatocyte apoptosis by downregulating Bax expression and TUNEL-positive staining, restoring the balance of cleaved-caspase-3 and caspase-3, and improving the antioxidant defense system to prevent oxidative damage in db/db mice. Conclusion: Compared to MET or exercise intervention alone, the combined exercise and metformin exhibited significant effect on ameliorating hepatic steatosis, inhibiting oxidative and ER stress-induced hepatocyte apoptosis via improving the capacity of the antioxidant defense system and suppression of the PERK-eIF2α-ATF4 pathway. Furthermore, upregulation of AMPK-Nrf2-HO-1 signaling pathway might be a key crosstalk between MET and exercise, which may have additive effects on alleviating hepatic lipid accumulation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose , Glicemia , Caspase 3/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estresse do Retículo Endoplasmático , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Hepatócitos/metabolismo , Hipoglicemiantes/farmacologia , Lipídeos , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Superóxido Dismutase-1/metabolismo , Proteína X Associada a bcl-2/metabolismo
3.
J Ethnopharmacol ; 299: 115692, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36084818

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hancornia speciosa Gomes (Apocynaceae) is a tree found in the Brazilian savannah, traditionally used to treat several diseases, including diabetes and hypertension. The anti-hypertensive activity of H. speciosa leaves (HSL) has been demonstrated in different models and is credited to the vasodilator effect and ACE (angiotensin-converting enzyme) inhibition. The hypoglycemic effect of HSL has been also reported. AIM OF THE STUDY: To establish correlations between the biological activities elicited by H. speciosa extracts and the contents of their major compounds, aiming to define chemical markers related to the potential antihypertensive and antidiabetic effects of the species. Additionally, it aimed to isolate and characterize the chemical structure of a marker related to the α-glucosidase inhibitory effect. MATERIALS AND METHODS: Extracts of a single batch of H. speciosa leaves were prepared by extraction with distinct solvents (ethanol/water in different proportions; methanol/ethyl acetate), employing percolation or static maceration as extraction techniques, at different time intervals. The contents of chlorogenic acid, rutin and FlavHS (a tri-O-glycoside of quercetin) were quantified by a developed and validated HPLC-PDA method. Bornesitol was determined by HPLC-PDA after derivatization with tosyl chloride, whereas total flavonoids were measured spectrophotometrically. Identification of other constituents in the extracts was performed by UPLC-DAD-ESI-MS/MS analysis. The vasorelaxant activity was assayed in rat aortic rings precontracted with phenylephrine, and α-glucosidase inhibition was tested in vitro. Principal component analysis (PCA) was employed to evaluate the contribution of each marker to the biological responses. Isolation of compound 1 was carried out by column chromatography and structure characterization was accomplished by NMR and UPLC-DAD-ESI-MS/MS analyses. RESULTS: The contents of the chemical markers (mean ± s.d. % w/w) varied significantly among the extracts, including total flavonoids (2.68 ± 0.14 to 5.28 ± 0.29), bornesitol (5.11 ± 0.26 to 7.75 ± 0.78), rutin (1.46 ± 0.06 to 1.97 ± 0.02), FlavHS (0.72 ± 0.05 to 0.94 ± 0.14) and chlorogenic acid (0.67 ± 0.09 to 0.91 ± 0.02). All extracts elicited vasorelaxant effect (pIC50 between 4.97 ± 0.22 to 6.48 ± 0.10) and α-glucosidase inhibition (pIC50 between 3.49 ± 0.21 to 4.03 ± 0.10). PCA disclosed positive correlations between the vasorelaxant effect and the contents of chlorogenic acid, rutin, total flavonoids, and FlavHS, whereas a negative correlation was found with bornesitol concentration. No significant correlation between α-glucosidase inhibition and the contents of the above-mentioned compounds was found. On the other hand, PCA carried out with the areas of the ten major peaks from the chromatograms disclosed positive correlations between a peak ascribed to co-eluted triterpenes and α-glucosidase inhibition. A triterpene was isolated and identified as 3-O-ß-(3'-R-hydroxy)-hexadecanoil-lupeol. CONCLUSION: According to PCA results, the vasorelaxant activity of H. speciosa extracts is related to flavonoids and chlorogenic acid, whereas the α-glucosidase inhibition is associated with lipophilic compounds, including esters of lupeol like 3-O-ß-(3'-R-hydroxy)-hexadecanoil-lupeol, described for the first time for the species. These compounds can be selected as chemical markers for the quality control of H. speciosa plant drug and derived extracts.


Assuntos
Apocynaceae , alfa-Glucosidases , Angiotensinas/análise , Animais , Anti-Hipertensivos/análise , Apocynaceae/química , Quimiometria , Ácido Clorogênico , Etanol , Flavonoides/análise , Glicosídeos/análise , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Metanol , Triterpenos Pentacíclicos , Fenilefrina , Extratos Vegetais/química , Folhas de Planta/química , Quercetina/análise , Ratos , Rutina/farmacologia , Solventes , Espectrometria de Massas em Tandem , Vasodilatadores/análise , Vasodilatadores/farmacologia , Água
4.
Iran J Med Sci ; 47(5): 484-493, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36117578

RESUMO

Background: Brown algae have gained worldwide attention due to their significant biological activities, such as antidiabetic properties. In the present study, the antidiabetic properties of six brown algae from the Persian Gulf were investigated. Methods: An experimental study was conducted from 2017 to 2019 to examine the inhibitory effects of six brown algae against the α-glucosidase activity. Methanol (MeOH) and 80% MeOH extracts of Colpomenia sinuosa, Sargassum acinaciforme, Iyengaria stellata, Sirophysalis trinodis, and two accessions of Polycladia myrica were analyzed. The effect of 80% MeOH extracts of Sirophysalis trinodis on blood glucose levels in streptozotocin-induced diabetic rats was evaluated. Chemical constituents of brown algae were analyzed using thin-layer chromatography and liquid chromatography-mass spectrometry techniques. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant. Results: The 80% MeOH extracts of Iyengaria stellata (IC50=0.33±0.15 µg/mL) and Colpomenia sinuosa (IC50=3.50±0.75 µg/mL) as well as the MeOH extracts of Colpomenia sinuosa (IC50=3.31±0.44 µg/mL) exhibited stronger inhibitory effect on α-glucosidase than the acarbose (IC50=160.15±27.52 µg/mL, P<0.001). The 80% MeOH extracts of Sirophysalis trinodis reduced postprandial blood glucose levels in diabetic rats compared to the control group (P=0.037). Fucoxanthin was characterized as the major antidiabetic agent in most of the algal extracts. Conclusion: Sirophysalis trinodis is recommended as a novel source for isolation and identification of potential antidiabetic compounds due to its high in vivo and in vitro antidiabetic effects.


Assuntos
Diabetes Mellitus Experimental , Feófitas , Acarbose , Animais , Glicemia/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Oceano Índico , Metanol , Feófitas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Estreptozocina/análise , alfa-Glucosidases
5.
BMC Complement Med Ther ; 22(1): 235, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064352

RESUMO

BACKGROUND: Lysiphyllum strychnifolium (Craib) A. Schmitz, a traditional Thai medicinal plant, is mainly composed of polyphenols and flavonoids and exhibits several pharmacological activities, including antioxidant, anticancer, antimicrobial, and antidiabetic activities. However, the mechanism by which pure compounds from L. strychnifolium inhibit glucose catalysis in the small intestine and their effect on the glucose transporter remain unknown. METHODS: The objectives of this research were to examine the effect of 3,5,7-trihydroxychromone-3-O-𝛼-L-rhamnopyranoside (compound 1) and 3,5,7,3',5'-pentahydroxy-flavanonol-3-O-𝛼-L-rhamnopyranoside (compound 2) on the inhibition of α-amylase and α-glucosidase, as well as glucose transporters, such as sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5), using Caco-2 cells as a model of human intestinal epithelial cells. Additionally, the binding affinity and interaction patterns of compounds against two receptor proteins (SGLT1 and GLUT2) were determined for the first time utilizing a molecular docking approach. RESULTS: In the α-amylase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The results indicated that compound 1 inhibited α-amylase activity in a manner similar to that of acarbose (which exhibit IC50 values of 3.32 ± 0.30 µg/mL and 2.86 ± 0.10 µg/mL, respectively) in addition to a moderate inhibitory effect for compound 2 (IC50 = 10.15 ± 0.53 µg/mL). Interestingly, compounds 1 and 2 significantly inhibited α-glucosidase and exhibited better inhibition than that of acarbose, with IC50 values of 5.35 ± 1.66 µg/mL, 510.15 ± 1.46 µg/mL, and 736.93 ± 7.02 µg/mL, respectively. Additionally, α-glucosidase activity in the supernatant of the Caco-2 cell monolayer was observed. In comparison to acarbose, compounds 1 and 2 inhibited α-glucosidase activity more effectively in Caco-2 cells without cytotoxicity at a concentration of 62.5 µg/mL. Furthermore, the glucose uptake pathways mediated by SGLT1, GLUT2, and GLUT5- were downregulated in Caco-2 cells treated with compounds 1 and 2. Additionally, molecular modeling studies revealed that compounds 1 and 2 presented high binding activity with SGLT1 and GLUT2. CONCLUSION: In summary, our present study was the first to perform molecular docking with compounds present in L. strychnifolium extracts. Our findings indicated that compounds 1 and 2 reduced glucose uptake in Caco-2 cells by decreasing the expression of glucose transporter genes and inhibiting the binding sites of SGLT1 and GLUT2. Therefore, compounds 1 and 2 may be used as functional foods in dietary therapy for postprandial hyperglycemia modulation of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Fabaceae , Acarbose , Células CACO-2 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Polifenóis , alfa-Amilases/metabolismo , alfa-Glucosidases/metabolismo
7.
Front Endocrinol (Lausanne) ; 13: 951570, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093105

RESUMO

Objective: To study the effects of liraglutide or lifestyle interventions combined with other antidiabetic drugs on glucose metabolism and abdominal fat distribution in patients with obesity and type 2 diabetes mellitus (T2DM). Methods: From April 30, 2020, to April 30, 2022, a prospective randomized controlled study was carried out at the Endocrinology Department of Beijing Hospital, the National Center of Gerontology. According to the in- and exclusion criteria and by the random table method, revisited T2DM patients were selected as the research subjects and were allocated into a Study group (taking liraglutide) and a Control group (underwent lifestyle interventions). All patients received continuous 12-weeks interventions to the endpoint, and the changes of value [Δ=(endpoint)-(baseline)] of physical measurements, blood tests, the energy spectrum CT examination results, and body composition analysis results were analyzed and compared. Results: A total of 85 people completed this study, and among them, 47 were in the Study group and 38 were in the Control group. Compared with the Control group, the changes of hemoglobin A1c (HbA1c) level (-0.78 ± 1.03% vs. -1.57 ± 2.00%, P=0.025), visceral fat area (0.91 ± 16.59 cm2 vs. -7.1 ± 10.17 cm2, P=0.011), and subcutaneous fat area of abdomen [0 (-18.75, 15.5) cm2 vs. -16.5 (-41.75, -2.25) cm2, P=0.014] were all greater in the Study group. The adverse events caused by liraglutide were mainly concentrated in the gastrointestinal system and all of them were minor adverse events. Conclusion: Liraglutide can be the drug of choice for weight management and reduction of abdominal fat distribution in patients with obesity and T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Liraglutida , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Gordura Intra-Abdominal/diagnóstico por imagem , Estilo de Vida , Liraglutida/farmacologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Estudos Prospectivos , Tomografia Computadorizada por Raios X
8.
Int J Mol Sci ; 23(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36077003

RESUMO

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.


Assuntos
Diabetes Mellitus Experimental , PPAR gama , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Glibureto/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Simulação de Acoplamento Molecular , PPAR gama/metabolismo , Quinazolinas/efeitos adversos , Ratos , Compostos de Sulfonilureia/efeitos adversos , Receptores de Sulfonilureias/agonistas
9.
Int J Mol Sci ; 23(17)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36077136

RESUMO

Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal. Today, we know a lot about the pathogenesis of atherosclerosis. However, the main knowledge is that the disease is extremely complicated. The development of atherosclerosis is associated with more than one molecular mechanism, each making a significant contribution. These mechanisms include endothelial dysfunction, inflammation, mitochondrial dysfunction, oxidative stress, and lipid metabolism disorders. This complexity inevitably leads to difficulties in treatment and prevention. One of the possible therapeutic options for atherosclerosis and its consequences may be metformin, which has already proven itself in the treatment of diabetes. Both diabetes and atherosclerosis are complex metabolic diseases, the pathogenesis of which involves many different mechanisms, including those common to both diseases. This makes metformin a suitable candidate for investigating its efficacy in cardiovascular disease. In this review, we highlight aspects such as the mechanisms of action and targets of metformin, in addition to summarizing the available data from clinical trials on the effective reduction of cardiovascular risks.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Diabetes Mellitus , Metformina , Aterosclerose/metabolismo , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Estresse Oxidativo
10.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36077491

RESUMO

Gestational diabetes mellitus (GDM) is a metabolic disease affecting an increasing number of pregnant women around the world. It is not only associated with numerous perinatal complications but also has long-term consequences impacting maternal health and fetal development. To prevent them, it is important to keep glucose levels under control. As much as 15-30% of GDM patients will require treatment with insulin, metformin, or glyburide. With that in mind, it is crucial to keep searching for novel and improved pharmacotherapies. Nowadays, there are ongoing studies investigating the use of other groups of drugs that have proven successful in the treatment of T2DM. Glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP-4) inhibitor are among the drugs targeting the incretin system and are currently receiving significant attention. The aim of our review is to demonstrate the potential of these medications in treating GDM and preventing its later complications. It seems that both groups may be successful in the GDM management used alone or as an addition to better-known drugs, including metformin and glyburide. However, more clinical trials are needed to confirm their importance in GDM treatment and to demonstrate effective therapeutic strategies.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Inibidores da Dipeptidil Peptidase IV , Metformina , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glibureto/uso terapêutico , Humanos , Hipoglicemiantes/farmacologia , Incretinas/uso terapêutico , Metformina/uso terapêutico , Gravidez
11.
Drug Des Devel Ther ; 16: 2919-2931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36068789

RESUMO

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is known to have anti-inflammatory and anti-oxidant effects on the brain, and its clinical potential in the treatment of cognitive impairment in diseases such as Alzheimer's disease (AD) and Parkinson disease (PD) is currently being explored. This review focused on the reported beneficial effects of pioglitazone on cognitive dysfunction and summarized the associated mechanisms associated with pioglitazone-induced improvement in cognitive dysfunction. Our review of the relevant literature indicated that there is conclusive evidence of the effect of pioglitazone on improving cognitive impairment via its agonistic effect on PPAR-γ. Further, several mechanisms of action have been reported, and these include enhanced NF-kB and p38 activity; regulation of the pro-inflammatory cytokines IL-1, IL-6, and TNF-α; inhibition of Aß production; alterations in the levels of mitochondrial proteins such as mitoNEET; regulation of protein kinases such as CDK5 and JNK; regulation of ROS and MDA levels and the levels of the antioxidant proteins TRX1 and PON2; and increased expression of thyroid hormone receptors. Despite these promising findings, pioglitazone treatment is also associated with cardiovascular risks, such as weight gain and edema, which subsequently increase the risk of mortality. Further, it has been documented that pioglitazone may be unable to cross the blood-brain barrier when administered in certain forms, and it can also cause cell death when administered at high concentrations. Therefore, further research is required to explore the effects of acute and chronic pioglitazone treatment on memory function and the associated risks, in order to determine its clinical applicability in the treatment of cognitive disorders. Nonetheless, the current literature does demonstrate that pioglitazone promotes the function of PPAR receptors in ameliorating inflammation, oxidative stress, amyloidogenesis, and hypothyroidism, and enhancing neurogenesis, synaptic plasticity, and mitochondrial function. Therefore, these mechanisms of PPAR receptors warrant further investigation in order to establish the clinical applicability of pioglitazone in the treatment of cognitive disorders, such as PD and AD, and neuronal impairment in conditions such as diabetes.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Parkinson , Tiazolidinedionas , Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico , Disfunção Cognitiva/complicações , Disfunção Cognitiva/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , PPAR gama/metabolismo , Doença de Parkinson/tratamento farmacológico , Pioglitazona , Tiazolidinedionas/farmacologia , Tiazolidinedionas/uso terapêutico
12.
Molecules ; 27(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36080485

RESUMO

Over the years, great attention has been paid to coumarin derivatives, a set of versatile molecules that exhibit a wide variety of biological activities and have few toxic side effects. In this study, we investigated the antidiabetic potential of 6-formyl umbelliferone (6-FU), a novel furanocoumarin isolated from Angelica decursiva. Numerous pharmacological activities of 6-FU have been previously reported; however, the mechanism of its antidiabetic activity is unknown. Therefore, we examined the action of 6-FU on a few candidate-signaling molecules that may underlie its antidiabetic activity, including its inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation (IC50 = 1.13 ± 0.12, 58.36 ± 1.02, 5.11 ± 0.21, and 2.15 ± 0.13 µM, respectively). A kinetic study showed that 6-FU exhibited mixed-type inhibition against α-glucosidase and HRAR and competitive inhibition of PTP1B. Docking simulations of 6-FU demonstrated negative binding energies and close proximity to residues in the binding pockets of those enzymes. We also investigated the molecular mechanisms underlying 6-FU's antidiabetic effects. 6-FU significantly increased glucose uptake and decreased PTP1B expression in insulin-resistant C2C12 skeletal muscle cells. Moreover, 6-FU (0.8-100 µM) remarkably inhibited the formation of fluorescent AGEs in glucose-fructose-induced human serum albumin glycation over the course of 4 weeks. The findings clearly indicate that 6-FU will be useful in the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-related complications.


Assuntos
Angelica , Diabetes Mellitus , Furocumarinas , Angelica/química , Diabetes Mellitus/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Umbeliferonas/farmacologia , Umbeliferonas/uso terapêutico , alfa-Glucosidases/metabolismo
13.
Medicine (Baltimore) ; 101(36): e30310, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086785

RESUMO

Sodium-glucose cotransporter 2 inhibitor (SGLT2I) is a new type of hypoglycemic drug that targets the kidney. As research continues to advance on this topic, it has been found that SGLT2I has multiple protective effects, such as hypoglycemic, cardio-renal protective, antihypertensive, and lipid-lowering effects. This review discusses the current concepts and possible mechanisms of SGLT2I in the treatment of heart failure, myocardial infarction, hypertension, cardiomyopathy and arrhythmia to provide a reference for clinicians to use drugs more reasonably and scientifically.


Assuntos
Sistema Cardiovascular , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Coração , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
14.
Expert Rev Clin Pharmacol ; 15(9): 1107-1117, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36065506

RESUMO

INTRODUCTION: Metformin has been recognized as the first-choice drug for type 2 diabetes mellitus (T2DM). The potency of metformin in the treatment of type 2 diabetes has always been in the spotlight and shown significant individual differences. Based on previous studies, the efficacy of metformin is related to the single-nucleotide polymorphisms of transporter genes carried by patients, amongst which a variety of gene polymorphisms of transporter and target protein genes affect the effectiveness and adverse repercussion of metformin. AREAS COVERED: Here, we reviewed the current knowledge about gene polymorphisms impacting metformin efficacy based on transporter and drug target proteins. EXPERT OPINION: The reason for the difference in clinical drug potency of metformin can be attributed to the gene polymorphism of drug transporters and drug target proteins in the human body. Substantial evidence shows that genetic polymorphisms in transporters such as organic cation transporter 1 (OCT1) and organic cation transporter 2 (OCT2) affect the glucose-lowering effectiveness of metformin. However, optimization of individualized dosing regimens of metformin is necessary to clarify the role of several polymorphisms.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Glucose , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Proteínas de Membrana Transportadoras , Metformina/farmacologia , Nucleotídeos , Transportador 1 de Cátions Orgânicos/genética , Transportador 1 de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/genética , Transportador 2 de Cátion Orgânico/uso terapêutico , Polimorfismo de Nucleotídeo Único
15.
J Dairy Sci ; 105(10): 8439-8453, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36055831

RESUMO

Hyperinsulinemia concurrent with hypoglycemia is one of a myriad of physiological changes typically experienced by lactating dairy cows exposed to heat stress, the consequences of which are not yet well defined or understood. Therefore, the objective of this experiment was to separate the production-related effects of hyperinsulinemia with hypoglycemia from those of a hyperthermic environment. Multiparous lactating Holstein cows (n = 23; 58 ± 4 d in milk, 3.1 ± 0.3 lactations) were housed in temperature-controlled rooms and all were subjected to 4 experimental periods as follows: (1) thermoneutral (TN; temperature-humidity index of 65.1 ± 0.2; d 1-5), (2) TN + hyperinsulinemic-hypoglycemic clamp (HHC; insulin infused at 0.3 µg/kg of BW per h, glucose infused to maintain 90 ± 10% of baseline blood glucose for 96 h; d 6-10), (3) heat stress (HS; temperature-humidity index of 72.5 ± 0.2; d 16-20), and (4) HS + euglycemic clamp (EC; glucose infused to reach 100 ± 10% of TN baseline blood glucose for 96 h; d 21-25). Cows were fed and milked twice daily. Feed refusals were collected once daily for calculation of daily dry matter intake, and milk samples were collected at the beginning and end of each period for component analyses. Circulating insulin concentrations were measured in daily blood samples, whereas glucose concentrations were measured more frequently and variably in association with clamp procedures. Rectal temperatures and respiration rates were greater during HS than TN, as expected, and states of hyperinsulinemia and hypoglycemia were successfully induced by the HHC and high ambient temperatures (HS and EC). Feed intake differed based upon thermal environment as it was similar during TN and HHC periods, and declined for HS and EC. Milk production was not entirely reflective of feed intake as it was greatest during TN, intermediate during HHC, and lowest during HS and EC. All milk components differed with the experimental period, primarily in response to the thermal environment. Interestingly, TN baseline glucose concentrations were highly correlated with the change in glucose from TN to HS, and were related to glycemic status during HS. Furthermore, although few in number, those cows that failed to become hypoglycemic during HS tended to have a greater reduction in milk yield. The work presented here addresses a critical knowledge gap by broadening our understanding of the physiological response to heat stress and the related changes in glycemic state. This broadened understanding is fundamental for the development of novel, innovative management strategies as the dairy industry is compelled to become increasingly efficient in spite of global warming.


Assuntos
Doenças dos Bovinos , Transtornos de Estresse por Calor , Hiperinsulinismo , Hipoglicemia , Insulinas , Animais , Glicemia , Bovinos , Dieta/veterinária , Feminino , Transtornos de Estresse por Calor/veterinária , Resposta ao Choque Térmico , Temperatura Alta , Hiperinsulinismo/veterinária , Hipoglicemia/veterinária , Hipoglicemiantes/farmacologia , Lactação/fisiologia , Leite
16.
J Ethnopharmacol ; 299: 115672, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064150

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The metabolic syndrome, which comprises hyperglycemia, dyslipidemia, abdominal obesity, and hypertension, is a worldwide problem. This disorder is a significant risk factor for insulin resistance, diabetes mellitus, cardiovascular disease incidence, and mortality. The value of herbs and natural products in the treatment of human ailments has been documented in several inquiries. An annual herbaceous plant called Portulaca oleracea L. (purslane) is used both as a traditional medicine and an edible plant to treat various ailments including gastrointestinal diseases and liver inflammation. Purslane contains a variety of secondary metabolites such as organic acids, flavonoids, terpenoids, and alkaloids. AIM OF THE STUDY: In the current work, our team aims to shed light on the potential efficacy of purslane and its main components in treating metabolic syndrome and its complications. STUDY DESIGN: Scopus, Google Scholar, and PubMed databases have been used to gather the most relevant in vitro, in vivo studies, and clinical trials from the time of inception up to February 2022. RESULTS: The effects of purslane on metabolism are among its most significant pharmacological properties. In patients with metabolic syndrome, purslane could significantly lower blood glucose and balance lipid profiles. This indicates that purslane might have a potential role in the management of metabolic syndrome through different underlying mechanisms including antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-obesity, and antidiabetic. CONCLUSION: According to previous investigations, purslane can control metabolic syndrome and its complications. However, further preclinical and clinical studies are required to approve the advantageous effects of purslane on metabolic syndrome.


Assuntos
Síndrome Metabólica , Portulaca , Anti-Inflamatórios , Antioxidantes , Glicemia , Flavonoides , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Lipídeos , Síndrome Metabólica/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Terpenos
17.
Molecules ; 27(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36080148

RESUMO

Taraxacum officinale (T. officinale), a wild vegetable with a number of health claims, has been mostly ignored and unexplored. The study aims to compare the nutritional, phytochemical as well as antidiabetic potential of fresh as well as shade-dried leaves of T. officinale, in order to recommend its best form as a dietary antidiabetic product. The results revealed that as compared to fresh leaves, the shade-dried leaves, in addition to possessing higher levels of carbohydrates, crude protein, crude fat, crude fiber, etc., also contain appreciable amounts of total phenols (5833.12 ± 4.222 mg/100), total flavonoids (188.84 ± 0.019 mg/100 g), ascorbic acid (34.70 ± 0.026 mg/100 g), ß-carotene (3.88 ± 1.473 mg/100 g) and total chlorophyll (239.51 ± 0.015 mg/100 g) antioxidants. The study revealed the presence of medicinally important antidiabetic flavonoid quercetin present in T. officinale leaves. Among the three solvent systems used, the aqueous extract of shade-dried T. officinale leaves comparatively demonstrated potent antidiabetic activity under in vitro conditions in a dose-dependent manner via targeting α-amylase and α-glucosidase, the two potent enzymes of carbohydrate metabolism. Therefore, in addition to being a nutritious herb, the shade-dried leaves of T. officinale have great potential to suppress post-prandial glucose rise and can be better exploited through clinical trials to be used as a dietary intervention for better management of diabetes.


Assuntos
Taraxacum , Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Taraxacum/química , alfa-Amilases
18.
Carbohydr Polym ; 296: 119954, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36087998

RESUMO

In this study, peach gum was sequentially extracted by water at 25 °C, 95 °C and 0.1 M NaOH, obtaining room temperature water-soluble (PG-WE), hot water-soluble (PG-HWE), and alkali-soluble (PG-AE) polysaccharide fractions. These three kinds of polysaccharide fractions exhibited a similar arabinogalactan structure according to FTIR spectrum and monosaccharide composition. However, their molecular weight and chain conformation were different based on high-performance size exclusion chromatography analysis, which resulted in different rheological behavior. PG-WE and PG-HWE presented non-Newtonian behavior, and the apparent viscosity of PG-WE was higher than that of PG-HWE at concentrations of 2.0 % and 3.0 % (w/w). Dynamic sweep tests showed that PG-HWE solutions behaved as viscous fluids, while PG-WE solutions tended to form gel-like structures at concentrations higher than 2 % (w/w). Furthermore, PG-WE showed significant in vitro inhibition against α-glucosidase activity in a dose-dependent manner and reduced the fluorescence of α-glucosidase through dynamic quenching mechanism.


Assuntos
Prunus persica , Carboidratos da Dieta , Hipoglicemiantes/farmacologia , Gomas Vegetais/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Temperatura , Água , alfa-Glucosidases
19.
Int J Nanomedicine ; 17: 4261-4275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36134204

RESUMO

Introduction: Nowadays, in nanotechnology and material science, biosynthesis of the metal nanoparticle is a promising approach. Methods: In the current research, the extract of the Korean Ueong dry root (BdkR), which belongs to the Asteraceae family, was used as a reducing and capping agent, for the green synthesis of the BdkR-Ag nanoparticles in a cost-effective and highly efficient manner. In this study for the reaction measures, UV-Vis spectroscopy was applied. SEM, EDX, FTIR, XRD, mean size distribution, and zeta potential were used for the characterization of the green synthesized BdkR-AgNPs. In the beginning, the primary phytochemical screening of BdkR extract was estimated and the cytotoxicity, antidiabetic, antioxidant, and antibacterial activities of the green synthesized BdkR-AgNPs were evaluated. Results: According to the results, the BdkR extract is rich in various phytochemicals and the generated AgNPs were crystalline in nature. The surface plasmon resonance value of the BdkR-AgNPs was 444 nm confirming the synthesis of AgNPs. The BdkR-AgNPs displayed four clear diffraction peaks at 2 theta angles (38.22); (46.15); (64.88); (76.83), respectively, which are equivalent to (111), (200), (220) and (311). The obtained nanoparticles have a zeta potential of -17.0 mV. Furthermore, the generated BdkR-AgNPs exhibited considerable antidiabetic effect in terms of the inhibition of α-glucosidase with a maximum inhibition value of 95.41% at 5.0 µg/mL and more than 86% inhibition at 2.5 µg/mL and the estimated IC50 value was found to be 0.653 µg/mL. Further, it also displayed a significant cytotoxicity activity against the HepG2 cancer cell lines at 10 µg/mL and 100 µg/mL concentrations with 86% and 88% of inhibition, respectively. Besides this, the synthesized AgNPs also displayed promising antioxidant activities in terms of the DPPH (IC50 value - 56.26 µg/mL), ABTS (IC50 value - 171.43 µg/mL) and reducing power (IC0.5 value - 227.42 µg/mL). Discussion: The multipotential effects of the synthesized BdkR-AgNPs might be attributed to the presence of the bioactive compounds in the BdkR extract that acted as the capping and reducing agent in the synthesis process. The green synthesized BdkR-AgNPs exhibited promising bioactive potential for their future applications in the food and biomedical field.


Assuntos
Nanopartículas Metálicas , Prata , Antibacterianos/química , Antioxidantes/química , Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Nanopartículas Metálicas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Substâncias Redutoras , República da Coreia , Prata/química , Prata/farmacologia , alfa-Glucosidases
20.
Biomed Pharmacother ; 153: 113441, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076556

RESUMO

Metformin (a widely used antidiabetic drug) has demonstrated efficacy in models of painful diabetic neuropathy (PDN), as well as certain clinical efficacy in relieving/preventing PDN. This study aimed to determine the type of interaction between metformin and duloxetine/oxycodone/eslicarbazepine acetate [ESL]/vitamin B12 in relieving diabetic pain hypersensitivity. Antihyperalgesic efficacy was determined using a Von Frey apparatus in mice with streptozotocin-induced PDN. We examined metformin's efficacy following oral (acute and prolonged 7-day treatment) and local (spinal and peripheral) application. The examined analgesics were administered in a single oral dose, whereas vitamin B12 was intraperitoneally administered for 7 days. In combination experiments, metformin (prolonged treatment) and analgesics/vitamin B12 were co-administered in fixed-dose fractions of their ED50 values and the type of interaction was determined using isobolographic analysis. Metformin produced dose-dependent antihyperalgesic effects in diabetic mice after oral (acute and prolonged 7-day treatment) and local spinal/peripheral application. Two-drug metformin combinations with analgesics/vitamin B12 also dose-dependently reduced mechanical hyperalgesia. The isobolographic analysis revealed that metformin synergises with analgesics/vitamin B12, with a 6-7 fold dose reduction of both drugs in the examined combinations. In conclusion, metformin reduces hyperalgesia in diabetic animals, most likely by acting at the spinal and peripheral level. Additionally, it synergizes with duloxetine/oxycodone/ESL/vitamin B12 in reducing hyperalgesia. Metformin co-treatment may increase analgesic efficacy and enable the use of lower (and potentially safer) analgesic doses for treating PDN. Combined metformin-vitamin B12 use may provide more effective pain relief and mitigate metformin-induced vitamin B12 deficiency.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Metformina , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/tratamento farmacológico , Cloridrato de Duloxetina/uso terapêutico , Hiperalgesia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Oxicodona/uso terapêutico , Dor/tratamento farmacológico , Vitamina B 12/farmacologia , Vitamina B 12/uso terapêutico , Vitaminas/uso terapêutico
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