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1.
Anticancer Res ; 41(7): 3481-3487, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34230143

RESUMEN

BACKGROUND/AIM: Metformin is an antidiabetic drug that has been reported to have antitumor activity in many cancer types. This study investigated the molecular mechanisms underlying the antitumor effect of metformin. MATERIALS AND METHODS: We investigated the molecular mechanism of the antitumor effect of metformin alone and in combination with AKT serine/threonine kinase (AKT) inhibition via cell viability and western blot analyses. RESULTS: Notably, metformin increased the phosphorylation of AKT at serine 473 using protein array screening. Metformin-induced AKT activation was markedly suppressed by siRNA targeting activating transcription factor 4 (ATF4) but not AMP-activated protein kinase α. These results indicate that AKT activation by metformin was induced in an ATF4-dependent and AMPKα-independent manner. Treatment using metformin combined with MK-2206, an AKT inhibitor, or a siRNA for AKT markedly reduced the viability of cells compared with those cells treated with these agents alone. In addition, MK-2206 increased cell sensitivity to the combination of metformin with ionizing radiation or cisplatin. CONCLUSION: Inhibition of AKT can enhance the antitumor effect of metformin and would be a promising strategy to sensitize non-small-cell lung cancer to a combination of metformin with radiation or cisplatin.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Metformina/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Hipoglucemiantes/farmacología , Neoplasias Pulmonares/metabolismo
2.
Molecules ; 26(11)2021 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-34199668

RESUMEN

Obesity is characterized by elevated infiltration of macrophages into adipose tissue, leading to the development of insulin resistance. The black soybean seed coat is a rich source of anthocyanins with antioxidative and anti-inflammatory activities. This study investigated the effects of black soybean anthocyanin extract (BSAn) on obesity-induced oxidative stress, the inflammatory response, and insulin resistance in a coculture system of hypertrophied 3T3-L1 adipocytes and RAW264 macrophages. Coculture of adipocytes with macrophages increased the production of reactive oxygen species and inflammatory mediators and cytokines (NO, MCP-1, PGE2, TNFα, and IL-6) and the release of free fatty acids but reduced anti-inflammatory adiponectin secretion. BSAn treatment (12.5, 25, 50, and 100 µg/mL) alleviated the coculture-induced changes (p < 0.001) and inhibited coculture-induced activation of JNK and ERK signaling (p < 0.01). BSAn also blocked the migration of RAW264.7 macrophages toward 3T3-L1 adipocytes. In addition, treatment with BSAn increased PPARγ expression and glucose uptake in response to insulin in hypertrophied 3T3-L1 adipocyte and RAW264.7 macrophage coculture (p < 0.01). These results demonstrate that BSAn attenuates inflammatory responses and improves adipocyte metabolic function in the coculture of hypertrophied 3T3-L1 adipocytes and RAW264.7 macrophages, suggesting the effectiveness of BSAn for obesity-induced insulin resistance.


Asunto(s)
Antocianinas/farmacología , Antiinflamatorios/farmacología , Hipoglucemiantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Soja/química , Células 3T3-L1 , Animales , Comunicación Celular/efectos de los fármacos , Técnicas de Cocultivo , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Resistencia a la Insulina , Ratones , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos
3.
Molecules ; 26(13)2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34206308

RESUMEN

Horse chestnut (Aesculus hippocastanum L.)-derived drugs have shown their potential in biomedical applications. The seed of A. hippocastanum contains various kinds of chemical compounds including phenolics, flavonoids, coumarins, and triterpene saponins. Here, we investigated the chemical components in A. hippocastanum L. grown in Uzbekistan, which has not yet been studied in detail. We identified 30 kinds of triterpene saponins in an extract of A. hippocastanum L. Classifying extracted saponins into eight fractions, we next studied the hypoglycemic and the anti-inflammatory activities of escin and its derivatives through in vivo experiments. We came by data indicating the highest (SF-1 and SF-2) and the lowest (SF-5 and SF-8) antidiabetic and anti-inflammatory effects of those eight fractions. These results imply the prospective use of A. hippocastanum L. grown in Uzbekistan in the production of pharmaceutical drugs to treat diabetes and inflammation.


Asunto(s)
Aesculus/química , Antiinflamatorios , Glicósidos , Hipoglucemiantes , Triterpenos , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Femenino , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Masculino , Ratas , Ratas Wistar , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Uzbekistán
4.
Molecules ; 26(13)2021 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-34206320

RESUMEN

Type 2 diabetes (T2D) is a chronic metabolic disease, which could affect the daily life of patients and increase their risk of developing other diseases. Synthetic anti-diabetic drugs usually show severe side effects. In the last few decades, plant-derived drugs have been intensively studied, particularly because of a rapid development of the instruments used in analytical chemistry. We tested the efficacy of Gundelia tournefortii L. (GT) in increasing the translocation of glucose transporter-4 (GLUT4) to the myocyte plasma membrane (PM), as a main strategy to manage T2D. In this study, GT methanol extract was sub-fractionated into 10 samples using flash chromatography. The toxicity of the fractions on L6 muscle cells, stably expressing GLUTmyc, was evaluated using the MTT assay. The efficacy with which GLUT4 was attached to the L6 PM was evaluated at non-toxic concentrations. Fraction 6 was the most effective, as it stimulated GLUT4 translocation in the absence and presence of insulin, 3.5 and 5.2 times (at 250 µg/mL), respectively. Fraction 1 and 3 showed no significant effects on GLUT4 translocation, while other fractions increased GLUT4 translocation up to 2.0 times. Gas chromatography-mass spectrometry of silylated fractions revealed 98 distinct compounds. Among those compounds, 25 were considered anti-diabetic and glucose disposal agents. These findings suggest that GT methanol sub-fractions exert an anti-diabetic effect by modulating GLUT4 translocation in L6 muscle cells, and indicate the potential of GT extracts as novel therapeutic agents for T2D.


Asunto(s)
Asteraceae/química , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Hipoglucemiantes , Células Musculares/metabolismo , Animales , Línea Celular , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Transportador de Glucosa de Tipo 4/genética , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Transporte de Proteínas/efectos de los fármacos , Ratas
5.
Phytomedicine ; 87: 153582, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34091150

RESUMEN

BACKGROUND AND PURPOSE: Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice. METHOD: Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation. RESULTS: Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. CONCLUSIONS: Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.


Asunto(s)
Corynebacterium glutamicum/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Flavonoides/farmacología , Hipoglucemiantes/farmacología , Animales , Glucemia/metabolismo , Proteínas de Unión al ADN/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/genética , Glucógeno/metabolismo , Insulina/sangre , Insulina/metabolismo , Masculino , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Ribosómico 16S , Factores de Transcripción/metabolismo
6.
Molecules ; 26(10)2021 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-34065194

RESUMEN

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 µM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 µM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.


Asunto(s)
Acetamidas/síntesis química , Acetamidas/farmacología , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacología , Tiazinas/química , Tiazinas/farmacología , Acetamidas/química , Acetamidas/uso terapéutico , Simulación por Computador , Diabetes Mellitus/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Tiazinas/síntesis química
7.
Int J Mol Sci ; 22(9)2021 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-34065108

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models. This review focuses on the pathogenesis of NASH-related HCC and the mechanisms by which metformin inhibits the initiation and progression of NASH-related HCC. Since the functional role of immune cells in liver homeostasis and pathogenesis is increasingly appreciated in developing anti-cancer therapies on liver malignancies, we discuss both the traditional targets of metformin in hepatocytes and the recently defined effects of metformin on immune cells.


Asunto(s)
Hipoglucemiantes/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Metformina/farmacología , Animales , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/prevención & control , Daño del ADN , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/prevención & control , Macrófagos/metabolismo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Estrés Oxidativo , Sustancias Protectoras/farmacología , Factores de Riesgo
8.
Molecules ; 26(10)2021 May 20.
Artículo en Inglés | MEDLINE | ID: covidwho-1248002

RESUMEN

Diabetes mellitus (DM) is a chronic disorder and has affected a large number of people worldwide. Insufficient insulin production causes an increase in blood glucose level that results in DM. To lower the blood glucose level, various drugs are employed that block the activity of the α-glucosidase enzyme, which is considered responsible for the breakdown of polysaccharides into monosaccharides leading to an increase in the intestinal blood glucose level. We have synthesized novel 2-(3-(benzoyl/4-bromobenzoyl)-4-hydroxy-1,1-dioxido-2H-benzo[e][1,2]thiazin-2-yl)-N-arylacetamides and have screened them for their in silico and in vitro α-glucosidase inhibition activity. The derivatives 11c, 12a, 12d, 12e, and 12g emerged as potent inhibitors of the α-glucosidase enzyme. These compounds exhibited good docking scores and excellent binding interactions with the selected residues (Asp203, Asp542, Asp327, His600, Arg526) during in silico screening. Similarly, these compounds also showed good in vitro α-glucosidase inhibitions with IC50 values of 30.65, 18.25, 20.76, 35.14, and 24.24 µM, respectively, which were better than the standard drug, acarbose (IC50 = 58.8 µM). Furthermore, a good agreement was observed between in silico and in vitro modes of study.


Asunto(s)
Acetamidas/síntesis química , Acetamidas/farmacología , Inhibidores de Glicósido Hidrolasas/síntesis química , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/farmacología , Tiazinas/química , Tiazinas/farmacología , Acetamidas/química , Acetamidas/uso terapéutico , Simulación por Computador , Diabetes Mellitus/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/uso terapéutico , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Tiazinas/síntesis química
9.
Molecules ; 26(11)2021 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-34073584

RESUMEN

PPARα is a ligand-dependent transcription factor and its activation is known to play an important role in cell defense through anti-inflammatory and antioxidant effects. MHY3200 (2-[4-(5-chlorobenzo[d]thiazol-2-yl)phenoxy]-2,2-difluoroacetic acid), a novel benzothiazole-derived peroxisome proliferator-activated receptor α (PPARα) agonist, is a synthesized PPARα activator. This study examined the beneficial effects of MHY3200 on age-associated alterations in reactive oxygen species (ROS)/Akt/forkhead box (FoxO) 1 signaling in rat kidneys. Young (7-month-old) and old (22-month-old) rats were treated with MHY3200 (1 mg/kg body weight/day or 3 mg/kg body weight/day) for two weeks. MHY3200 treatment led to a notable decrease in triglyceride and insulin levels in serum from old rats. The elevated kidney ROS level, serum insulin level, and Akt phosphorylation in old rats were reduced following MHY3200 treatment; moreover, FoxO1 phosphorylation increased. MHY3200 treatment led to the increased level of FoxO1 and its target gene, MnSOD. MHY3200 suppressed cyclooxygenase-2 expression by activating PPARα and inhibiting the activation of nuclear factor-κB (NF-κB) in the kidneys of old rats. Our results suggest that MHY3200 ameliorates age-associated renal inflammation by regulating NF-κB and FoxO1 via ROS/Akt signaling.


Asunto(s)
Envejecimiento/efectos de los fármacos , Inflamación/tratamiento farmacológico , Riñón/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , PPAR alfa/agonistas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Peso Corporal , Regulación de la Expresión Génica , Hipoglucemiantes/farmacología , Insulina/metabolismo , Riñón/patología , Masculino , PPAR alfa/metabolismo , Fosforilación , Unión Proteica , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Triglicéridos/metabolismo
10.
J Ayub Med Coll Abbottabad ; 33(2): 188-191, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34137526

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive disease due to multiple pathophysiological defects. Monotherapy alone cannot achieve adequate glycemic control and can lead to treatment failure. Empagliflozin, a sodium-glucose cotransporter2 (SGLT2) inhibitor improves glycemic control in patients with T2DM. There were limited studies to determine efficacy and safety profile of empagliflozin with conventional oral antidiabetic drugs (OADs) in Pakistan. So we investigated the efficacy and safety profile of empagliflozin as add-on therapy to metformin and sitagliptin in T2DM patients. METHODS: In this comparative randomized placebo-controlled trial, 240 obese type 2 diabetic patients with inadequate glycaemic control (i.e, HbA1c ≥7%) with metformin and sitagliptin were allocated in to two groups. Patients in group B were given tab empagliflozin 10mg twice a day while patients in group A were given tab placebo for a period of 24 weeks. Changes in body weight, HbA1c, blood pressure were analysed pre and post treatment by using SPSS v23. RESULTS: Empagliflozin caused a significant reduction in body weight -6.9±2.4 kg as compared to placebo -3.1±0.8 kg with p-value <0.001. This body weight reduction was further accompanied by reduction in systolic blood pressure -10.1±2.6 mmHg in empagliflozin group versus -5.3±2.5 mmHg in placebo group with p-value <0.001, and HbA1c -1.68±0.45 in empagliflozin group versus -0.1±0.06 in placebo group with p-value <0.001. There were 28.3% patients in empagliflozin group in whom HbA1c levels reduced <7% as compared to only 13.3% patients in placebo group (p-value 0.04). However no significant adverse effects were recorded in both study groups. CONCLUSIONS: Empagliflozin as a combination therapy has good efficacy and safety profile in obese type 2 diabetic patients.


Asunto(s)
Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Adulto , Compuestos de Bencidrilo/administración & dosificación , Compuestos de Bencidrilo/farmacología , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Método Doble Ciego , Quimioterapia Combinada , Femenino , Glucósidos/administración & dosificación , Glucósidos/farmacología , Hemoglobina A Glucada/análisis , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Masculino , Persona de Mediana Edad , Placebos , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacos
11.
J Food Sci ; 86(7): 3046-3060, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34146413

RESUMEN

This study aimed to assess the biological properties of peptide fractions isolated from dried fermented dairy products (jameed) as influenced by processing. Peptide fractions were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) from salted (Sa) and unsalted (Us) cow milk jameed after drying the fermented curd by sun drying (Sd) or freeze-drying (Fd) and were characterized for their antioxidant capacity and inhibitory activity toward angiotensin I-converting enzyme (ACE) and α-amylase. Sd samples showed more numerous peptide peaks in RP-HPLC chromatograms than Fd samples, regardless of the salt content. High antioxidant activity was evidenced in several peptide fractions from FdUs jameed (including fractions 1, 2, 4, 7, 8, 9, and 10), SdUs jameed (1, 2, 5, 7, and 9), and FdSa jameed (2, 5, 6, and 9). By contrast, peptide fractions from SdSa (1, 2, 3, 5, 8, and 9), SdUs (4, 5, and 10), and FdUs (5, 6, and 8) jameed displayed the highest ACE inhibitory activity. Similarly, the highest inhibition of α-amylase was obtained with fractions from SdSa (1, 2, 3, 4, 5, 6, 8, and 9), SdUs (2 and 6), and FdUs (1, 7 and 9) jameed. A significant negative correlation was evidenced between antioxidant activity and anti-α-amylase activity of peptide fractions from SdSa jameed. These findings demonstrate that cow milk jameed is a source of bioactive peptides with antioxidant, anti-ACE, and anti-α-amylase properties in vitro, which can be tailored by adjusting the salt content and the drying conditions. PRACTICAL APPLICATION: This study shows that cow milk jameed, a staple fermented food in several Mediterranean countries, can serve as a useful source of multifunctional bioactive peptides with potential antioxidant, hypotensive, and hypoglycemic effects, which may help prevent and manage chronic health conditions such as hypertension, type 2 diabetes, and the metabolic syndrome. The bioactivities of certain peptide fractions were enhanced by lowering the salt content of jameed or by the drying method. The relatively simple RP-HPLC method described in this study can be used to isolate the peptide fractions of interest for further characterization and use as functional ingredients.


Asunto(s)
Aminoácidos/análisis , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacocinética , Antioxidantes/farmacología , Productos Lácteos Cultivados , Hipoglucemiantes/farmacología , Leche/química , Fragmentos de Péptidos/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Animales , Antihipertensivos/química , Antioxidantes/química , Bovinos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipoglucemiantes/química , Fragmentos de Péptidos/química , Peptidil-Dipeptidasa A/metabolismo
12.
Int J Mol Sci ; 22(11)2021 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34072216

RESUMEN

Cheonggukjang (CGJ, fermented soybean paste), a traditional Korean fermented dish, has recently emerged as a functional food that improves blood circulation and intestinal regulation. Considering that excessive consumption of refined salt is associated with increased incidence of gastric cancer, high blood pressure, and stroke in Koreans, consuming CGJ may be desirable, as it can be made without salt, unlike other pastes. Soybeans in CGJ are fermented by Bacillus strains (B. subtilis or B. licheniformis), Lactobacillus spp., Leuconostoc spp., and Enterococcus faecium, which weaken the activity of putrefactive bacteria in the intestines, act as antibacterial agents against pathogens, and facilitate the excretion of harmful substances. Studies on CGJ have either focused on improving product quality or evaluating the bioactive substances contained in CGJ. The fermentation process of CGJ results in the production of enzymes and various physiologically active substances that are not found in raw soybeans, including dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids. These components prevent atherosclerosis, oxidative stress-mediated heart disease and inflammation, obesity, diabetes, senile dementia, cancer (e.g., breast and lung), and osteoporosis. They have also been shown to have thrombolytic, blood pressure-lowering, lipid-lowering, antimutagenic, immunostimulatory, anti-allergic, antibacterial, anti-atopic dermatitis, anti-androgenetic alopecia, and anti-asthmatic activities, as well as skin improvement properties. In this review, we examined the physiological activities of CGJ and confirmed its potential as a functional food.


Asunto(s)
Productos Biológicos , Fermentación , Alimentos Funcionales , Soja , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antihipertensivos/química , Antihipertensivos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Productos Biológicos/química , Productos Biológicos/farmacología , Ingredientes Alimentarios , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipolipemiantes/química , Hipolipemiantes/farmacología , Estructura Molecular , Evaluación Nutricional , Osteogénesis/efectos de los fármacos , Probióticos , Soja/química , Soja/metabolismo , Soja/microbiología
13.
Food Chem ; 361: 129866, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34091399

RESUMEN

This study investigated the in vitro bioactivities of extracts obtained from viscera, spines, shells, and gonads of Stomopneustes variolaris using subcritical water extraction (SWE) at 110 °C, 150 °C, 190 °C, and 230 °C and Soxhlet extraction. The highest amounts of phenolics (22.68 ± 0.05 mg GAE/g), flavonoids (27.11 ± 0.10 mg RE/g), and proteins (40.25 ± 0.84 mg BSA/g) were recorded from gonads at 230 °C, whereas maximum sugar content (23.38 ± 1.30 mg glucose/g) was in viscera at 150 °C. Gonads at 230 °C exhibited the highest DPPH activity (78.68 ± 0.18%), whereas viscera at 150 °C exhibited the highest ABTS+ (98.92 ± 1.27%) and protein denaturation inhibition activity (37.13 ± 9.94%). Viscera at 110 °C claimed the highest amylase inhibition (42.46 ± 0.83%), and spines at 150 °C had the highest anticancer activity (IC50 = 767.47 µg/mL). SWE achieved superior results in bioactive compound recovery and detected higher levels of bioactivities (p < 0.05). Results suggest processing sea urchin extracts via SWE has potential application to the food and pharmaceutical industries.


Asunto(s)
Productos Biológicos/farmacología , Fraccionamiento Químico/métodos , Erizos de Mar/química , Animales , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Productos Biológicos/aislamiento & purificación , Evaluación Preclínica de Medicamentos , Flavonoides/análisis , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Tecnología Química Verde , Células HeLa , Humanos , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Fenoles/análisis , Fenoles/aislamiento & purificación , Fenoles/farmacología , Agua/química
14.
Food Res Int ; 145: 110383, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34112386

RESUMEN

Diabetes is a metabolic disorder that has caused enormous harm to the public health worldwide. In this study, we evaluated the potential of phenolic compounds on diabetes management, addressing their mechanisms of action, in addition to discussing the digestion, absorption, metabolism, bioavailability, and toxic effects of these compounds. The intake of phenolic compounds can play a fundamental role on diabetes management, since they can reduce blood glucose levels, oxidative stress, protein glycation, inhibit the activity of dipeptidyl peptidase - IV and other key enzymes related to carbohydrate metabolism, activate various biochemical pathways to improve pancreatic ß-cell functions, increase insulin secretion, and improve insulin resistance. In this way, they can be considered a potential strategy in the development of pharmaceutical approaches that aim to reduce complications resulting from the progression of this metabolic pathology.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Células Secretoras de Insulina , Humanos , Hipoglucemiantes/farmacología , Polifenoles
15.
Medicine (Baltimore) ; 100(23): e26295, 2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34115034

RESUMEN

BACKGROUND: Obesity and insulin resistance (IR) are common in polycystic ovary syndrome (PCOS), which contribute to reproductive and metabolic abnormalities. Metformin increases insulin sensitivity, but it is associated with unsatisfied benefits of weight loss. Recent studies have reported that glucagon-like peptide 1 (GLP-1) receptor agonists improve IR and reduce weight in women with PCOS. We conducted a systematic review and meta-analysis to compare the effects between GLP-1 receptor agonists and metformin, and between GLP-1 receptor agonist-metformin combination and GLP-1 receptor agonists in overweight/obese women with PCOS on anthropometric, metabolic, reproductive outcomes. METHODS: Databases including PubMed, EMBASE, Web of Science, and Cochrane Library were selected to search for randomized controlled trials (RCTs) published in English up to March 2020. Eligible studies were identified according to the inclusion criteria. The primary outcomes included menstrual frequency, body mass index (BMI), total testosterone, and the homeostatic model assessment of insulin resistance. GRADE criteria were implemented to assess the quality of evidence for primary outcomes. RESULTS: Seven RCTs were selected for analysis, comprising 464 overweight/obese women with PCOS. In the low-quality evidence, a meta-analysis demonstrated that GLP-1 receptor agonists showed better effects relative to metformin on the reduction of body mass index (mean difference - 1.72; 95% confidence interval -2.46 to -0.99, P < .001) and homeostatic model assessment of insulin resistance (standard mean difference -0.37; 95% confidence interval - 0.60,- 0.15, P = .001). Moreover, the combination therapy exhibited similar effects on primary outcomes relative to GLP-1 receptor agonist alone. GLP-1 receptor agonists were also found to be associated with lower abdominal girth compared to metformin. A meta-analysis of gastrointestinal discomfort showed no significant difference between GLP-1 receptor agonist and metformin therapies, and between the combination therapy and GLP-1 receptor agonist alone. CONCLUSIONS: GLP-1 receptor agonists appear to be more beneficial for weight loss and IR improvement compared to metformin for overweight/obese women with PCOS. However, the combination treatment displays comparable effects with GLP-1 receptor agonist alone. The incidence of gastrointestinal discomforts was similar in different groups. However, the quality of the body of evidence is "low." Further prospective RCTs and cost-effectiveness analyses are also warranted to guide GLP-1 receptor agonists to treat women with PCOS.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón/agonistas , Metformina/farmacología , Síndrome del Ovario Poliquístico , Pérdida de Peso/efectos de los fármacos , Femenino , Humanos , Hipoglucemiantes/clasificación , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
Int J Mol Sci ; 22(10)2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-34069559

RESUMEN

Metformin is a drug in the family of biguanide compounds that is widely used in the treatment of type 2 diabetes (T2D). Interestingly, the therapeutic potential of metformin expands its prescribed use as an anti-diabetic drug. In this sense, it has been described that metformin administration has beneficial effects on different neurological conditions. In this work, we review the beneficial effects of this drug as a neuroprotective agent in different neurological diseases, with a special focus on epileptic disorders and Lafora disease, a particular type of progressive myoclonus epilepsy. In addition, we review the different proposed mechanisms of action of metformin to understand its function at the neurological level.


Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Metformina/uso terapéutico , Animales , Sistema Nervioso Central/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Modelos Animales de Enfermedad , Epilepsia/tratamiento farmacológico , Humanos , Hipoglucemiantes/farmacología , Enfermedad de Lafora/tratamiento farmacológico , Metformina/metabolismo , Metformina/farmacología , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología
17.
Life Sci ; 278: 119574, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-33961850

RESUMEN

AIMS: Dipeptidyl peptidase 4 (DPP-4) is a valid molecular drug target from which its inhibitors have been developed as medicines for treating diabetes. The present study evaluated a new synthetic DPP-4-specific inhibitor of small molecule DBPR108 for pharmacology and pharmacokinetic profiles. MAIN METHODS: DBPR108 of various doses was orally administered to rats, diabetic mice, and dogs and the systemic circulating DPP-4 activities in the animals were measured to demonstrate the pharmacological mechanisms of action via DPP-4 inhibition. Upon an oral administration of DBPR108, the serum active GLP-1 and insulin levels of the rats challenged with an oral glucose ingestion were measured. Oral glucose tolerance test in diet-induced obese mice was performed to examine if DBPR108 increases the glucose tolerability in animals. KEY FINDINGS: Orally administered DBPR108 inhibited the systemic plasma DPP-4 activities in rats, dogs and diabetic mice in a dose-dependent manner. DBPR108 caused elevated serum levels of active GLP-1 and insulin in the rats. DBPR108 dose-dependently increased the glucose tolerability in diet-induced obese (DIO) mice and, furthermore, DIO mice treated with DBPR108 (0.1 mg/kg) in combination with metformin (50 or 100 mg/kg) showed a prominently strong increase in the glucose tolerability. SIGNIFICANCE: DBPR108 is a novel DPP-4-selective inhibitor of small molecule that demonstrated potent in vivo pharmacological effects and good safety profiles in animals. DBPR108 is now a drug candidate being further developed in the clinical studies as therapeutics for treating diabetes.


Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/farmacología , Administración Oral , Animales , Área Bajo la Curva , Peso Corporal , Diabetes Mellitus Experimental/tratamiento farmacológico , Dipeptidil Peptidasa 4/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Perros , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/farmacocinética , Insulina/metabolismo , Venas Yugulares/patología , Masculino , Metformina , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Ratas , Ratas Sprague-Dawley , Especificidad de la Especie
18.
Life Sci ; 278: 119632, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34019900

RESUMEN

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.


Asunto(s)
Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Descubrimiento de Drogas , Terapia Molecular Dirigida , Transducción de Señal/efectos de los fármacos , Animales , Complicaciones de la Diabetes/genética , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/patología , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico
19.
Food Res Int ; 143: 110281, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33992381

RESUMEN

In this study, H2O2-Vc (hydrogen peroxide-ascorbic acid) oxidation system under 50 and 70 °C was developed to degrade blue honeysuckle polysaccharides. The results suggested that viscosity-average molecular weight was decreased and reducing sugar content was raised with the rise of time or temperature. The degradation was fitted to the second-order reaction kinetics. The gas chromatography revealed two degraded polysaccharides were consisted of six monosaccharides (Gal A, Rha, Ala, Gal, Glu, Man) with different ratios, and eight types of sugar residues were confirmed using nuclear magnetic resonance. Based on the linearity (R1), branching (R2), branch size (R3) calculation, PD70 (purified degraded polysaccharide at 70 °C) had a more linear structure and longer side chains comparing to PD50 (purified degraded polysaccharide at 50 °C). The absence of triple helical structure and sheet-like aggregation with rough surface were confirmed by the Congo red test and scanning electron. Rheological characterization proved the two degraded polysaccharides exhibited shear-thinning behavior and viscoelastic property. Besides, the two degraded polysaccharides displayed strong antiglycation activities, inhibitory effects against α-amylase and α-glucosidase, and exhibited competitive inhibitory kinetics. These findings support the potential application of blue honeysuckle polysaccharides as the treatment of diabetes.


Asunto(s)
Hipoglucemiantes , Lonicera , Polisacáridos/farmacología , Peróxido de Hidrógeno , Hipoglucemiantes/farmacología , Lonicera/química , alfa-Glucosidasas
20.
Mol Biol Rep ; 48(4): 3733-3745, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33988797

RESUMEN

Phenolic compounds, present in plants, are considered to be indispensable parts of human dietary sources. Sinapic acid, is a natural herbal compound containing phenolic acid. It is found in oranges, grapefruits, and cranberries and in herbs like canola, mustard seed and rapeseed. Sinapic acid is chemically studied as a cinnamic acid derivative that contains 3, 5-dimethoxyl and 4-hydroxyl substitutions in the phenyl group of cinnamic acid. Sinapic acid has been pharmacologically evaluated for its potent antioxidant, anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, anti-diabetic, anxiolytic and anti-bacterial activities. In this review we have summarized the potential pharmacological and therapeutic effects of Sinapic acid in various models.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antineoplásicos/uso terapéutico , Antioxidantes/uso terapéutico , Ácidos Cumáricos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Animales , Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Ácidos Cumáricos/farmacología , Humanos , Hipoglucemiantes/farmacología , Fármacos Neuroprotectores/farmacología
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