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1.
JAMA ; 330(22): 2182-2190, 2023 12 12.
Article in English | MEDLINE | ID: mdl-38085312

ABSTRACT

Importance: Insulin is recommended for pregnant persons with preexisting type 2 diabetes or diabetes diagnosed early in pregnancy. The addition of metformin to insulin may improve neonatal outcomes. Objective: To estimate the effect of metformin added to insulin for preexisting type 2 or diabetes diagnosed early in pregnancy on a composite adverse neonatal outcome. Design, Setting, and Participants: This randomized clinical trial in 17 US centers enrolled pregnant adults aged 18 to 45 years with preexisting type 2 diabetes or diabetes diagnosed prior to 23 weeks' gestation between April 2019 and November 2021. Each participant was treated with insulin and was assigned to add either metformin or placebo. Follow-up was completed in May 2022. Intervention: Metformin 1000 mg or placebo orally twice per day from enrollment (11 weeks -<23 weeks) through delivery. Main Outcome and Measures: The primary outcome was a composite of neonatal complications including perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy. Prespecified secondary outcomes included maternal hypoglycemia and neonatal fat mass at birth, and prespecified subgroup analyses by maternal body mass index less than 30 vs 30 or greater and those with preexisting vs diabetes early in pregnancy. Results: Of the 831 participants randomized, 794 took at least 1 dose of the study agent and were included in the primary analysis (397 in the placebo group and 397 in the metformin group). Participants' mean (SD) age was 32.9 (5.6) years; 234 (29%) were Black, and 412 (52%) were Hispanic. The composite adverse neonatal outcome occurred in 280 (71%) of the metformin group and in 292 (74%) of the placebo group (adjusted odds ratio, 0.86 [95% CI 0.63-1.19]). The most commonly occurring events in the primary outcome in both groups were preterm birth, neonatal hypoglycemia, and delivery of a large-for-gestational-age infant. The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Prespecified secondary outcomes and subgroup analyses were similar between groups. Of individual components of the composite adverse neonatal outcome, metformin-exposed neonates had lower odds to be large for gestational age (adjusted odds ratio, 0.63 [95% CI, 0.46-0.86]) when compared with the placebo group. Conclusions and Relevance: Using metformin plus insulin to treat preexisting type 2 or gestational diabetes diagnosed early in pregnancy did not reduce a composite neonatal adverse outcome. The effect of reduction in odds of a large-for-gestational-age infant observed after adding metformin to insulin warrants further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02932475.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetes, Gestational , Hypoglycemic Agents , Insulin , Metformin , Adult , Female , Humans , Infant, Newborn , Pregnancy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes, Gestational/drug therapy , Hypoglycemia/chemically induced , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Infant, Newborn, Diseases/chemically induced , Infant, Newborn, Diseases/etiology , Infant, Newborn, Diseases/prevention & control , Insulin/administration & dosage , Insulin/adverse effects , Insulin/therapeutic use , Insulin, Regular, Human/therapeutic use , Metformin/administration & dosage , Metformin/adverse effects , Metformin/therapeutic use , Premature Birth/chemically induced , Premature Birth/epidemiology , Premature Birth/etiology , Adolescent , Young Adult , Middle Aged
2.
JAMA ; 330(16): 1547-1556, 2023 10 24.
Article in English | MEDLINE | ID: mdl-37786390

ABSTRACT

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.


Subject(s)
Diabetes, Gestational , Metformin , Adult , Female , Humans , Infant, Newborn , Pregnancy , Birth Weight , Diabetes, Gestational/drug therapy , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin/therapeutic use , Metformin/administration & dosage , Metformin/adverse effects , Metformin/therapeutic use , Double-Blind Method
3.
Int. j. med. surg. sci. (Print) ; 9(3): 1-16, sept. 2022. graf, tab, ilus
Article in English | LILACS | ID: biblio-1518675

ABSTRACT

Cyperus esculentus L. (tiger nut) is a tuberous plant that promotes and protects reproductive functions, which are usually hampered in diabetics. The present study investigated the effect of Cyperus esculentus tuber extract (CETE) on testicular histology and sperm viability of alloxan-induced hyperglycaemic Wistar rats. Twenty-five adult male Wistar rats weighing 150-200g and grouped into five (n=5): Group 1, the control, administered tap water (20mL/kg), while groups 2-5 were administered a single intraperitoneal dose (120mg/kg b.w.) of alloxan, and each further received orally tap water (20mL/kg), CETE (100mg/kg), CETE (500 mg/kg) and metformin (500 mg/kg), respectively for 21 days. The animals were sacrificed, their sperm collected for analysis, while the testes were harvested, and processed for histology. Results showed significantly increased (p<0.05) blood glucose and testosterone, and significantly decreased (p<0.05) sperm pH, motility, count, morphology and density, as well as disruptions and hypertrophy of the spermatogenic and Sertoli cells of the hyperglycaemic group. There were significant (p<0.05) blood glucose decline, while the sperm parameters and testicular weight improved with normal testicular histology in the 100 mg/kg CETE, 500 mg/kg CETE, and metformin-treated groups compared to the control and hyperglycaemic group. Treatment with CETE showed blood glucose amelioration and improved sperm quality, as well as testicular damage attenuation.


Cyperus esculentus L. es una planta tuberosa que promueve y protege las funciones reproductivas, que generalmente se ven afectadas en los diabéticos. El presente estudio investigó el efecto del extracto de tubérculo de Cyperus esculentus (CETE) sobre la histología testicular y la viabilidad de los espermatozoides de ratas wistar con hiperglicemia inducida por alloxan. Veinticinco ratas Wistar macho adultas que pesaban 150-200 g y se agruparon en cinco (n = 5): el grupo 1, el control, administró agua del grifo (20ml / kg), mientras que los grupos 2-5 se les administró una dosis intraperitoneal única (120 mg / kg p.v.) de alloxan, y agua del grifo por vía oral (20ml/kg), CETE (100 mg/kg), CETE (500 mg/kg) y metformina (500 mg/kg), respectivamente durante 21 días. Los animales fueron sacrificados, su esperma recolectada para su análisis, mientras que los testículos fueron retirados y procesados para histología. Los resultados mostraron un aumento significativo (p<0,05) de la glucosa en sangre y la testosterona, y una disminución significativa (p<0,05) del pH, la motilidad, el recuento, la morfología y la densidad de los espermatozoides, así como interrupciones e hipertrofia de las células espermatogénicas y sertoli del grupo hiperglucémico. Hubo una disminución significativa (p<0,05) de la glucosa en sangre, mientras que los parámetros espermáticos y el peso testicular mejoraron con la histología testicular normal en los grupos de 100 mg / kg de CETE, 500 mg / kg de CETE y tratados con metformina en comparación con el grupo de control e hiperglucémico. El tratamiento con CETE mostró una mejora de la glucosa en sangre y una mejora de la calidad de los espermatozoides, así como atenuación del daño testicular.


Subject(s)
Animals , Male , Rats , Testis/drug effects , Plant Extracts/administration & dosage , Cyperus/chemistry , Hyperglycemia/drug therapy , Organ Size , Sperm Count , Sperm Motility/drug effects , Spermatozoa/drug effects , Testosterone , Blood Glucose/drug effects , Body Weight , Plant Extracts/pharmacology , Analysis of Variance , Rats, Wistar , Disease Models, Animal , Alloxan , Hydrogen-Ion Concentration , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage
4.
Más Vita ; 4(2): 368-385, jun. 2022. tab, graf
Article in Spanish | LILACS, LIVECS | ID: biblio-1392663

ABSTRACT

La diabetes tipo 2 es un trastorno metabólico progresivo complejo, que representa una amenaza significativa para la salud humana y representa más del 91% de todos los casos de diabetes. Objetivo: evaluar el efecto de la adición de tintura de Notholaena nivea al tratamiento con metformina en pacientes con tolerancia alterada a la glucosa (IGT) y diabetes de tipo 2 (DMT2). Materiales y Método: Ensayo clínico unicentral, aleatorizado, simple ciego, controlado con placebo. Todos los participantes con diagnóstico de IGT y DMT2 que tomaban metformina fueron asignados aleatoriamente a recibir kits con tintura de Notholaena nivea autentica (40 pacientes) o placebo (58 pacientes), fijando 6 gotas diarias, 30 minutos antes del desayuno y almuerzo durante 26 semanas, se hicieron 3 controles (0, 13 y 26 semanas) midiendo glucosa plasmática en ayunas (FPG), nivel de hemoglobina glucosilada (HbA1C) y perfil lipídico. Resultados: del grupo de tratamiento (tintura de Notholaena nivea más metformina) fueron significativamente eficientes a las 13 semanas de iniciado el ensayo, manteniendo la directriz de reducción de glucosa plasmática (FPG), al iniciar el estudio el grupo control y tratamiento obtuvieron niveles de FPG similares con valores de .57±1.7 y 7.84±1.9 mmol/l respectivamente (p>0.05), a las 13 semanas se redujo a 7.21±1.mmol/l para el grupo control y 6.49±2.33 mmol/l para el grupo tratamiento (p<0.01), mientras que a la semana 26 el grupo control reporto 7.09±1.41 mmol/l en tanto el grupo tratamiento obtuvo 5.98±0.71 mmol/l (p<0.01). Hubo reducción de los niveles de HbA1C dentro de los grupos, pero no se evidenciaron diferencias por efecto del tratamiento. En el perfil lipídico el tratamiento de Metformina sola evidencio una mejor respuesta con la reducción de colesterol total y aumento de lipoproteínas de alta densidad (HDL) pero aumento la concentración de triglicéridos, mientras que el tratamiento con tintura de Notholaena nivea mantuvo los perfiles lipídicos al igual que en un inicio (p>0.05). Conclusiones: el tratamiento combinado de metformina más tintura de Notholaena nivea reduce acelerada y eficazmente las concentraciones de FPG en sangre de pacientes con IGT o DMT2, pero es ineficaz en el tratamiento del perfil lipídico(AU)


Type 2 diabetes is a complex progressive metabolic disorder, which represents a significant threat to human health and accounts for more than 91% of all diabetes cases. Objective: to evaluate the effect of adding Notholaena nivea tincture to metformin treatment in patients with impaired glucose tolerance (IGT) and type 2 diabetes (DMT2). Materials and Method: Unicentral, randomized, single-blind, placebo-controlled clinical trial. All participants diagnosed with IGT and T2DM who were taking metformin were randomly assigned to receive authentic Notholaena nivea tincture kits (40 patients) or placebo (58 patients), setting 6 drops daily, 30 minutes before breakfast and lunch for 26 weeks. , 3 controls were made (0, 13 and 26 weeks) measuring fasting plasma glucose (FPG), glycosylated hemoglobin level (HbA1C) and lipid profile. Results: the treatment group (Notholaena nivea tincture plus metformin) were significantly efficient at 13 weeks from the start of the trial, maintaining the plasma glucose reduction guideline (FPG), at the start of the study the control and treatment groups obtained levels of Similar FPG with values of .57±1.7 and 7.84±1.9 mmol/l respectively (p>0.05), at 13 weeks it was reduced to 7.21±1.mmol/l for the control group and 6.49±2.33 mmol/l for the treatment group (p<0.01), while at week 26 the control group reported 7.09±1.41 mmol/l while the treatment group obtained 5.98±0.71 mmol/l (p<0.01). There was a reduction in HbA1C levels within the groups, but no differences due to treatment effect were observed. In the lipid profile, the treatment with Metformin alone showed a better response with the reduction of total cholesterol and an increase in high-density lipoproteins (HDL) but increased the concentration of triglycerides, while the treatment with Notholaena nivea tincture maintained the lipid profiles at the same as at the beginning (p>0.05). Conclusions: the combined treatment of metformin plus Notholaena nivea tincture rapidly and effectively reduces FPG concentrations in the blood of patients with IGT or DMT2, but it is ineffective in the treatment of the lipid profile.Keywords: Type 2 diabetes, Notholaena nivea, FPG, Metformin, lipid(AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Glucose Intolerance , Diabetes Mellitus, Type 2 , Metformin/administration & dosage , Patients , Exercise , Nutrition Therapy , Healthy Lifestyle , Glucose
5.
Int J Mol Sci ; 22(24)2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34948457

ABSTRACT

High-fat diet (HFD)-induced comorbid cognitive and behavioural impairments are thought to be the result of persistent low-grade neuroinflammation. Metformin, a first-line medication for the treatment of type-2 diabetes, seems to ameliorate these comorbidities, but the underlying mechanism(s) are not clear. Pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are neuroprotective peptides endowed with anti-inflammatory properties. Alterations to the PACAP/VIP system could be pivotal during the development of HFD-induced neuroinflammation. To unveil the pathogenic mechanisms underlying HFD-induced neuroinflammation and assess metformin's therapeutic activities, (1) we determined if HFD-induced proinflammatory activity was present in vulnerable brain regions associated with the development of comorbid behaviors, (2) investigated if the PACAP/VIP system is altered by HFD, and (3) assessed if metformin rescues such diet-induced neurochemical alterations. C57BL/6J male mice were divided into two groups to receive either standard chow (SC) or HFD for 16 weeks. A further HFD group received metformin (HFD + M) (300 mg/kg BW daily for 5 weeks) via oral gavage. Body weight, fasting glucose, and insulin levels were measured. After 16 weeks, the proinflammatory profile, glial activation markers, and changes within the PI3K/AKT intracellular pathway and the PACAP/VIP system were evaluated by real-time qPCR and/or Western blot in the hypothalamus, hippocampus, prefrontal cortex, and amygdala. Our data showed that HFD causes widespread low-grade neuroinflammation and gliosis, with regional-specific differences across brain regions. HFD also diminished phospho-AKT(Ser473) expression and caused significant disruptions to the PACAP/VIP system. Treatment with metformin attenuated these neuroinflammatory signatures and reversed PI3K/AKT and PACAP/VIP alterations caused by HFD. Altogether, our findings demonstrate that metformin treatment rescues HFD-induced neuroinflammation in vulnerable brain regions, most likely by a mechanism involving the reinstatement of PACAP/VIP system homeostasis. Data also suggests that the PI3K/AKT pathway, at least in part, mediates some of metformin's beneficial effects.


Subject(s)
Diet, High-Fat/adverse effects , Encephalitis/drug therapy , Metformin/administration & dosage , Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism , Vasoactive Intestinal Peptide/metabolism , Amygdala/drug effects , Amygdala/metabolism , Animals , Case-Control Studies , Down-Regulation , Encephalitis/chemically induced , Encephalitis/genetics , Encephalitis/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Metformin/pharmacology , Mice , Mice, Inbred C57BL , Pituitary Adenylate Cyclase-Activating Polypeptide/genetics , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Signal Transduction/drug effects , Vasoactive Intestinal Peptide/genetics
6.
Eur J Pharmacol ; 913: 174590, 2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34801530

ABSTRACT

Nutraceuticals are principally extracted from natural products that are frequently safe and well-tolerated. Lycopene and berberine are natural plants with a wide range of beneficial effects including protective activities against metabolic disorders such as diabetes and cardiovascular diseases. These compounds might be considered technically more as a drug than a nutraceutical and could be prescribed as a product. However, further studies are needed to understand if these supplements could affect metabolic syndrome outcomes. Even if nutraceuticals exert a prophylactic activity within the body, their bioactivity and bioavailability have high interindividual variation, and precise assessment of biological function of these bioactive compounds in randomized clinical trials is critical. However, these reports must be interpreted with more considerations due to the low quality of the trials. The aim of this paper is to bring evidence about the management of cardiovascular diseases and diabetes through the use of nutraceuticals with particular attention to lycopene and berberine effectiveness.


Subject(s)
Berberine/administration & dosage , Cardiovascular Diseases/therapy , Diabetes Mellitus/therapy , Dietary Supplements , Lycopene/administration & dosage , Berberine/pharmacokinetics , Biological Availability , Combined Modality Therapy/methods , Drug Evaluation, Preclinical , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Lycopene/pharmacokinetics , Metformin/administration & dosage , Randomized Controlled Trials as Topic , Treatment Outcome
7.
Nutrients ; 13(7)2021 Jul 11.
Article in English | MEDLINE | ID: mdl-34371883

ABSTRACT

The aim of the study was to evaluate the overall biohumoral and metabolic effects of a 12-week add-on therapy consisting of a new nutraceutical formulation (BHC) based on berberine, hesperidin, and chromium picolinate in type 2 diabetes mellitus (T2D) patients with suboptimal glycemic compensation receiving metformin. After 12 weeks, participants in the group receiving metformin plus BHC, compared to the group receiving metformin only, saw a significant improvement in their glucose profile, in terms of both glycated hemoglobin (HbA1c) and fasting blood glucose (FBG). Their FBG dropped from 145 ± 20 mg/dL to 128 ± 23 mg/dL (p < 0.01), a decrease of 11.7% compared with the baseline. This decrease differed significantly from the situation in the control arm (p < 0.05). HbA1c decreased by 7.5% from the baseline, from 53.5 ± 4.3 mmol/mol to 49.5 ± 5.1 mmol/mol (p < 0.01), in the group given BHC, while no difference was seen in the control group. Advanced glycation end products (AGEs) and malondialdehyde (MDA) were found to be significantly reduced (p < 0.01) only in the BHC group, from 9.34 ± 7.61 µg/mL to 6.75 ± 6.13 µg/mL, and from 1.7 ± 0.15 µmol/L to 1.4 ± 0.25 µmol/L, respectively. In patients with T2D taking metformin with suboptimal glycemic compensation, adding BHC for 3 months significantly improved glucose control in terms of FBG and HbA1c, and had a positive effect on the lipid peroxidation profile, as indicated by a decrease in AGEs and MDA.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Dietary Supplements , Glycemic Control/methods , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Aged , Blood Glucose/drug effects , Diabetes Mellitus, Type 2/blood , Drug Therapy, Combination , Female , Glycated Hemoglobin/drug effects , Humans , Male , Middle Aged , Treatment Outcome
8.
J Zhejiang Univ Sci B ; 22(7): 548-562, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-34269008

ABSTRACT

Metformin, a first-line drug for type 2 diabetes mellitus, has been recognized as a potential anti-tumor agent in recent years. Epigallocatechin-3-gallate (EGCG), as the dominant catechin in green tea, is another promising adjuvant agent for tumor prevention. In the present work, the potential effect of EGCG on the anti-tumor efficacy of metformin in a mouse melanoma cell line (B16F10) was investigated. Results indicated that EGCG and metformin exhibited a synergistic effect on cell viability, migration, and proliferation, as well as signal transducer and activator of transcription 3/nuclear factor-κB (STAT3/NF-κB) pathway signaling and the production of inflammation cytokines. Meanwhile, the combination showed an antagonistic effect on cell apoptosis and oxidative stress levels. The combination of EGCG and metformin also differentially affected the nucleus (synergism) and cytoplasm (antagonism) of B16F10 cells. Our findings provide new insight into the potential effects of EGCG on the anti-tumor efficacy of metformin in melanoma cells.


Subject(s)
Antineoplastic Agents/pharmacology , Catechin/analogs & derivatives , Melanoma/drug therapy , Metformin/administration & dosage , Skin Neoplasms/drug therapy , Animals , Apoptosis , Catechin/administration & dosage , Cell Line, Tumor , Cell Movement , Cell Nucleus/metabolism , Cell Proliferation , Cell Survival , Cytokines/metabolism , Cytoplasm/metabolism , Inflammation , Melanoma, Experimental , Mice , NF-kappa B p50 Subunit/metabolism , Oxidative Stress , Phosphorylation , STAT3 Transcription Factor/metabolism , Spectrum Analysis, Raman
9.
Behav Brain Res ; 414: 113475, 2021 09 24.
Article in English | MEDLINE | ID: mdl-34280460

ABSTRACT

Oxandrolone (OXA) is an androgen and anabolic steroid (AAS) that is used to reverse weight loss associated with some medical conditions. One of the side effects of OXA is its potential to induce depressive symptoms. Growing evidence suggested that neuroinflammation and cytokines play crucial roles in sickness behavioral and associated mood disturbances. Previous studies showed that metformin attenuated neuroinflammation. This study investigated the potential protective role of metformin against OXA-induced depression-like behavior and neuroinflammation. Twenty- four Wistar male rats were randomly grouped into four groups: the control group (Control) received only vehicle; the oxandrolone group (OXA) received oxandrolone (0.28 mg/kg, i.p); the metformin group (MET) received metformin (100 mg/kg, i.p); and the oxandrolone / metformin group (OXA + MET) received both oxandrolone (0.28 mg/kg, i.p) and metformin (100 mg/kg, i.p). These treatments were administered for fourteen consecutive days. Behavioral tests to measure depression-like behavior were conducted before and after treatments. qRT-PCR was used to measure the relative expression of proinflammatory and anti-inflammatory cytokines in the hippocampus and hypothalamus. The results showed that oxandrolone induced depression-like behavior and dysregulated pro-/anti-inflammatory cytokines, while metformin attenuated these effects. These findings suggest that metformin is a potential treatment to reverse the depressive effects induced by oxandrolone that involve neuroinflammatory effects.


Subject(s)
Anabolic Agents/adverse effects , Anti-Inflammatory Agents/pharmacology , Cytokines/drug effects , Depression/chemically induced , Depression/drug therapy , Metformin/pharmacology , Neuroinflammatory Diseases/chemically induced , Neuroinflammatory Diseases/drug therapy , Oxandrolone/adverse effects , Anabolic Agents/administration & dosage , Animals , Anti-Inflammatory Agents/administration & dosage , Behavior, Animal/drug effects , Depression/immunology , Depression/metabolism , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/immunology , Hippocampus/metabolism , Hypothalamus/drug effects , Hypothalamus/immunology , Hypothalamus/metabolism , Interleukin-10 , Interleukin-1beta/drug effects , Interleukin-6 , Male , Metformin/administration & dosage , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/metabolism , Oxandrolone/administration & dosage , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/drug effects
10.
Fluids Barriers CNS ; 18(1): 28, 2021 Jun 22.
Article in English | MEDLINE | ID: mdl-34158083

ABSTRACT

BACKGROUND: The blood-brain barrier (BBB) plays a critical role in protecting the central nervous system (CNS) from blood-borne agents and potentially harmful xenobiotics. Our group's previous data has shown that tobacco smoke (TS) and electronic cigarettes (EC) affect the BBB integrity, increase stroke incidence, and are considered a risk factor for multiple CNS disorders. Metformin was also found to abrogate the adverse effects of TS and EC. METHODS: We used sucrose and mannitol as paracellular markers to quantitatively assess TS and EC's impact on the BBB in-vitro. Specifically, we used a quantitative platform to determine the harmful effects of smoking on the BBB and study the protective effect of metformin. Using a transwell system and iPSCs-derived BMECs, we assessed TS and EC's effect on sucrose and mannitol permeability with and without metformin pre-treatment at different time points. Concurrently, using immunofluorescence (IF) and Western blot (WB) techniques, we evaluated the expression and distribution of tight junction proteins, including ZO-1, occludin, and claudin-5. RESULTS: Our data showed that TS and EC negatively affect sucrose and mannitol permeability starting after 6 h and up to 24 h. The loss of barrier integrity was associated with a reduction of TEER values. While the overall expression level of ZO-1 and occludin was not significantly downregulated, the distribution of ZO-1 was altered, and discontinuation patterns were evident through IF imaging. In contrast to occludin, claudin-5 expression was significantly decreased by TS and EC, as demonstrated by WB and IF data. CONCLUSION: In agreement with previous studies, our data showed the metformin could counteract the negative impact of TS and EC on BBB integrity, thus suggesting the possibility of repurposing this drug to afford cerebrovascular protection.


Subject(s)
Blood-Brain Barrier/metabolism , E-Cigarette Vapor/adverse effects , Metformin/administration & dosage , Neuroprotection/drug effects , Smoke/adverse effects , Tight Junctions/metabolism , Tobacco Products , Blood-Brain Barrier/drug effects , Capillary Permeability/drug effects , Capillary Permeability/physiology , Cell Survival/drug effects , Cell Survival/physiology , Claudin-5/metabolism , Drug Evaluation, Preclinical/methods , E-Cigarette Vapor/administration & dosage , Humans , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Neuroprotection/physiology , Occludin/metabolism , Tight Junctions/drug effects , Zonula Occludens-1 Protein/metabolism
11.
J Nutr Biochem ; 97: 108798, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34102283

ABSTRACT

Diabetic cardiomyopathy is a primary cause of increased morbidity and mortality in diabetics. Evidence has suggested a pivotal role for interrupted mitochondrial dynamics and quality control machinery in the onset and development of diabetic cardiomyopathy. Sequestosome 1 (SQSTM1) is a major reporter of selective autophagic activity. Other than controlling the expression of genes involved in mitochondrial biogenesis, recently peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) was reported to directly affect SQSTM1 gene expression. Calcineurin, a pivotal mediator of cardiac hypertrophy, has been also linked to enhanced expression of SQSTM1. This study aimed to test the cardioprotective effects of adding ω-3 polyunsaturated fatty acids (PUFAs) to metformin in a rat model of type 2 diabetes mellitus and to evaluate the molecular mechanisms underlying their effects on mitochondrial quality. Diabetes was induced in male Sprague Dawley rats by a high-fat diet for 6 weeks, followed by a low-dose streptozotocin (35 mg/kg). Diabetic rats were either treated with metformin (150 mg/kg/d), ω-3 PUFAs (300 mg/kg/d), or their combination in the same doses for further 8 weeks. Along with metabolic and pathological derangements, we report that correlating with electron microscopic evidence of mitochondrial degeneration, gene expression of the autophagic indicators SQSTM1, PGC-1α, and calcineurin were decreased in the hearts of diabetic rats. Independent of its anti-hyperglycemic effects, metformin successfully preserved mitochondrial integrity and upregulated myocardial PGC-1α, calcineurin, and SQSTM1 gene expression. ω-3 PUFAs possess synergistic cardioprotection when added to metformin, suggested by improvements in myocardial ultrastructure, autophagic activity, and SQSTM1 gene expression.


Subject(s)
Autophagy , Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/prevention & control , Fatty Acids, Omega-3/administration & dosage , Metformin/administration & dosage , Animals , Calcineurin/genetics , Calcineurin/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Diabetic Cardiomyopathies/metabolism , Diet, High-Fat , Male , Mitochondria, Heart/metabolism , Mitochondria, Heart/ultrastructure , Myocardium/metabolism , Myocardium/ultrastructure , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Rats , Rats, Sprague-Dawley , Sequestosome-1 Protein/genetics , Sequestosome-1 Protein/metabolism , Up-Regulation
12.
Drug Res (Stuttg) ; 71(6): 302-306, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33684953

ABSTRACT

OBJECTIVE: Antihyperglycemic activity of Thymoquinone (TQ) was evaluated in diabetic mouse model and patients. METHODS: TQ (50 mg/kg) was orally administered daily for 21 days in combination with metformin in diabetic mice and a reduction on blood glucose level was monitored. In human, a 90-day randomized study was carried out in 60 Type 2 Diabetes mellitus patients to evaluate safety and efficacy of TQ administration with metformin in a 3-arm study. Patients in arm 1 (T1) received 1 tablet of metformin SR 1000 mg and 1 tablet of TQ 50 mg once daily. The second arm (T2) patients received 1 tablet of metformin SR 1000 mg and 2 tablets of TQ 50 mg once daily. Patients in arm 3 (R) received 1 tablet of metformin SR 1000 mg only. RESULTS: The diabetic mice treated with combination of TQ and metformin showed significant decrease in blood sugar compared to those treated with only metformin. In patients who completed the study, the glycated hemoglobin (HbA1c) values in T1, T2 and R decreased after 3 months from 7.2, 7.2 and 7.3 to 6.7, 6.8, and 7.1, respectively. A greater reduction in Fasting Blood Glucose and Post Prandial Blood Glucose was also observed in T1 and T2 arms compared to R. CONCLUSION: At dose levels of 50 and 100 mg of TQ combined with a daily dose of 1000 mg Metformin demonstrated a reduction in the levels of HbA1c and blood glucose compared to the standard treatment of diabetic patients with metformin alone.


Subject(s)
Benzoquinones/administration & dosage , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Administration, Oral , Adult , Animals , Blood Glucose/analysis , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/diagnosis , Drug Evaluation, Preclinical , Drug Therapy, Combination/methods , Female , Glycated Hemoglobin/analysis , Humans , Male , Mice , Middle Aged , Prospective Studies , Streptozocin/administration & dosage , Streptozocin/toxicity
13.
ScientificWorldJournal ; 2021: 6672277, 2021.
Article in English | MEDLINE | ID: mdl-33531880

ABSTRACT

Natural polymers have become attractive to pharmaceutical researchers and manufacturers as excipients because of the advantages they possess relative to their semisynthetic and synthetic counterparts. Although pectin from some natural sources has been investigated for use in the pharmaceutical industry as excipients, pectin from okra, which is readily available and used as food in many parts of the world, has not been extensively investigated as a potential control-releasing agent in tablets. This study thus seeks to determine the drug release modifying properties of okra pectin from 6 different genotypes of okra cultivated and available in Ghana. Pectin was extracted from different genotypes of okra, physicochemical properties were characterized, and control release matrix tablets of metformin (F1-F6) were formulated using the wet granulation method with the okra pectin as the drug release modifier, respectively. The drug content, in vitro drug release, and mathematical kinetic modeling of drug release from the matrix tablets were studied. Drug release profiles of formulated matrix tablets were compared to an existing (innovator) brand of metformin sustained-release tablet on the market using the similarity and difference factors, respectively. The extracted pectin had percentage yields ranging from 6 to 20% w/w with swelling indexes and water-holding capacities between 300-500% and 9-10 mL/g, respectively, and pH within 6.20-6.90. All the formulated batches passed the drug content test (90-105%) and produced the optimal release of metformin (>80%) after 24 hours. Different batches of formulated tablets exhibited different mechanisms of drug release with batches F1, F2, F5, and F6 being similar (ƒ2 values being >50 and ƒ1 values <15) to the innovator brand. Pectin from the 6 different genotypes of okra studied has the potential for use as drug release modifiers in pharmaceutical manufacturing of control release matrix tablets and production of more affordable medicines.


Subject(s)
Abelmoschus/chemistry , Drug Carriers/chemistry , Pectins/chemistry , Tablets/chemistry , Chemical Phenomena , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Liberation , Kinetics , Metformin/administration & dosage , Phytochemicals/chemistry , Plant Extracts/chemistry , Solubility
14.
Phytomedicine ; 83: 153470, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33524703

ABSTRACT

BACKGROUND: Breast cancer is the first leading cause of women cancer-related deaths worldwide. While there are many proposed treatments for breast cancer, low efficacy, toxicity, and resistance are still major therapeutic obstacles. Thus, there is a need for safer and more effective therapeutic approaches. Because of the direct link between obesity and carcinogenesis, energy restriction mimetic agents (ERMAs) such as the antidiabetic agent, metformin was proposed as a novel antiproliferative agent. However, the anticancer dose of metformin alone is relatively high and impractical to be implemented safely in patients. The current work aimed to sensitize resistant breast cancer cells to metformin's antiproliferative effect using the natural potential anticancer agent, tangeretin. METHODS: The possible synergistic combination between metformin and tangeretin was initially evaluated using MTT cell viability assay in different breast cancer cell lines (MCF-7, MDA-MB-231, and their resistant phenotype). The possible mechanisms of synergy were investigated via Western blotting analysis, reactive oxygen species (ROS) measurement, annexin/PI assay, cell cycle analysis, and wound healing assay. RESULTS: The results indicated the ability of tangeretin to improve the anticancer activity of metformin. Interestingly, the improved activity was almost equally observed in both parental and resistant cancer cells, which underlines the importance of this combination in cases of the emergence of resistance. The synergy was mediated through the enhanced activation of AMPK and ROS generation in addition to the improved inhibition of cell migration, induction of cell cycle arrest, and apoptosis in cancer cells. CONCLUSION: The current work underscores the importance of metformin as an ERMA in tackling breast cancer and as a novel approach to boost its anticancer activity via a synergistic combination with tangeretin.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Apoptosis/drug effects , Breast Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , Drug Resistance, Neoplasm/drug effects , Female , Flavones/administration & dosage , Humans , MCF-7 Cells , Metformin/administration & dosage
15.
Nutrients ; 14(1)2021 Dec 24.
Article in English | MEDLINE | ID: mdl-35010938

ABSTRACT

The aim of this study was to examine the efficacy of intensive medical nutrition therapy (MNT) plus metformin in preventing gestational diabetes mellitus (GDM) among high-risk Mexican women. An open-label randomized clinical trial was conducted. Inclusion criteria were pregnant women with three or more GDM risk factors: Latino ethnic group, maternal age >35 years, body mass index >25 kg/m2, insulin resistance, and a history of previous GDM, prediabetes, a macrosomic neonate, polycystic ovarian syndrome, or a first-degree relative with type 2 diabetes. Women before 15 weeks of gestation were assigned to group 1 (n = 45): intensive MNT-plus metformin (850 mg twice/day) or group 2 (n = 45): intensive MNT without metformin. Intensive MNT included individual dietary counseling, with ≤50% of total energy from high carbohydrates. The primary outcome was the GDM incidence according to the International Association of Diabetes Pregnancy Study Groups criteria. There were no significant differences in baseline characteristics and adverse perinatal outcomes between the groups. The GDM incidence was n = 11 (24.4%) in the MNT plus metformin group versus n = 7 (15.5%) in the MNT without metformin group: p = 0.42 (RR: 1.57 [95% CI: 0.67-3.68]). There is no benefit in adding metformin to intensive MNT to prevent GDM among high-risk Mexican women. Clinical trials registration: NCT01675310.


Subject(s)
Diabetes, Gestational/prevention & control , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Nutrition Therapy/methods , Pregnancy Complications/prevention & control , Adolescent , Adult , Body Mass Index , Female , Humans , Hypoglycemic Agents/therapeutic use , Infant, Newborn , Maternal Age , Medical History Taking , Mexico , Middle Aged , Pregnancy , Young Adult
16.
Naunyn Schmiedebergs Arch Pharmacol ; 394(4): 591-602, 2021 04.
Article in English | MEDLINE | ID: mdl-33064168

ABSTRACT

Selenium nanoparticles (SeNPs) are well reported to exhibit pharmacological activities both in vitro and in vivo. However, literature is devoid of studies on the impact of SeNPs and/or metformin (M) against streptozotocin (STZ)-mediated oxidative brain injury and behavioral impairment. Consequently, to fill this gap, diabetes was induced in male Wistar rats by feeding with 10% fructose solution for 2 weeks, followed by a single dose intraperitoneal injection of STZ (40 mg/kg body weight [bwt]). After rats were confirmed diabetic, they were treated orally with 0.1 mg/kg bwt of SeNPs ± M (50 mg/kg bwt), and normal control (NC) received citrate buffer (2 mg/mL) for 5 weeks. In comparison with the diabetic control (DC), SeNPs, and/or M significantly (p < 0.05) lowered blood glucose levels, but increased insulin secretion and pancreatic ß-cell function. An increase in locomotor and motor activities evidenced by improved spontaneous alternation, locomotor frequency, hinding, and increased mobility time were observed in treated groups. In addition, there was enhanced brain antioxidant status with a lower acetylcholinesterase (AChE) activity and oxidative-inflammatory stress biomarkers. A significant downregulation of caspase 3 and upregulation of parvalbumin and Nrf2 protein expressions was observed in treated groups. In some of the studied parameters, treated groups were statistically (p < 0.05) insignificant compared with the normal control (NC) group. Overall, co-treatment elicited more efficacy than that of the individual regimen.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Metformin/administration & dosage , Nanoparticles/administration & dosage , Selenium/administration & dosage , Acetylcholinesterase/metabolism , Animals , Behavior, Animal/drug effects , Brain/drug effects , Brain/metabolism , Caspase 3/metabolism , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Drug Therapy, Combination , Glutathione/metabolism , Glutathione Transferase/metabolism , Insulin/blood , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Male , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Oxidoreductases/metabolism , Parvalbumins/metabolism , Rats, Wistar
17.
J Ethnopharmacol ; 281: 113548, 2021 Dec 05.
Article in English | MEDLINE | ID: mdl-33152427

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Huangkui capsule (HKC), extracted from Abelmoschus manihot (L.) medic (AM), as a patent proprietary Chinese medicine on the market for approximately 20 years, has been clinically used to treat chronic glomerulonephritis. Renal fibrosis has been implicated in the onset and development of diabetic nephropathy (DN). However, the potential application of HKC for preventing DN has not been evaluated. AIM OF THE STUDY: This study was designed to investigate the efficacy and underlying mechanisms of HKC combined with metformin (MET), the first-line medication for treating type 2 diabetes, in the treatment of renal interstitial fibrosis. MATERIALS AND METHODS: A rat model of diabetes-associated renal fibrosis was established by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) combined with a high-fat and high-glucose diet. The rats were randomly divided into five groups: normal control, DN, HKC (1.0 g/kg/day), MET (100 mg/kg/d), and HKC plus MET (1.0 g/kg/day + 100 mg/kg/d). Following drug administration for 8 weeks, we collected blood, urine, and kidney tissue for analysis. Biochemical markers and metabolic parameters were detected using commercial kits. Histopathological staining was performed to monitor morphological changes in the rat kidney. High-glucose-induced human kidney HK-2 cells were used to evaluate the renal protective effects of HKC combined with MET (100 µg/mL+10 mmol/L). MTT assay and acridine orange/ethidium bromide were used to examine cell proliferation inhibition rates and apoptosis. Immunofluorescence assay and Western blot analysis were performed to detect renal fibrosis-related proteins including Klotho, TGF-ß1, and phosphorylated (p)-p38. RESULTS: Combination therapy (HKC plus MET) significantly improved the weight, reduced blood glucose (BG), blood urea nitrogen (BUN), total cholesterol (T-CHO), triglycerides (TG), low-density lipoprotein (LDL) and increased the level of high-density lipoprotein (HDL) of DN rats. Combination therapy also significantly reduced urine serum creatinine (SCR) and urine protein (UP) levels as well as reduced the degrees of renal tubule damage and glomerulopathy in DN rats. Combination therapy ameliorated renal fibrosis, as evidenced by reduced levels of alpha-smooth muscle actin and fibronectin and increased expression of E-cadherin in the kidneys. Moreover, HKC plus MET alleviated the degree of DN in part via the Klotho/TGF-ß1/p38MAPK signaling pathway. In vitro experiments showed that combination therapy significantly inhibited cell proliferation and apoptosis and regulated fibrosis-related proteins in high-glucose (HG)-induced HK-2 cells. Further studies revealed that combination therapy suppressed cell proliferation and fibrosis by inhibiting the Klotho-dependent TGF-ß1/p38MAPK pathway. CONCLUSIONS: HKC plus MET in combination suppressed abnormal renal cell proliferation and fibrosis by inhibiting the Klotho-dependent TGF-ß1/p38MAPK pathway. Collectively, HKC combined with MET effectively improved DN by inhibiting renal fibrosis-associated proteins and blocking the Klotho/TGF-ß1/p38MAPK signaling pathway. These findings improve the understanding of the pathogenesis of diabetes-associated complications and support that HKC plus MET combination therapy is a promising strategy for preventing DN.


Subject(s)
Diabetic Nephropathies/chemically induced , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal/pharmacology , Klotho Proteins/metabolism , Metformin/pharmacology , Transforming Growth Factor beta1/metabolism , Animals , Cell Line , Cell Proliferation/drug effects , Diabetes Mellitus, Experimental , Diet, High-Fat/adverse effects , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Gene Expression Regulation/drug effects , Glucose/administration & dosage , Glucose/adverse effects , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Klotho Proteins/genetics , Male , Metformin/administration & dosage , Phytotherapy , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/genetics , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism
18.
Pharm Biol ; 58(1): 1123-1130, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33191822

ABSTRACT

CONTEXT: HuoxueJiangtang decoction (ZY) is a traditional Chinese medicine for the treatment of diabetes. OBJECTIVE: The protective effect of ZY on renal injury in diabetic nephropathy rats was investigated in this study. MATERIALS AND METHODS: Fifty 4-week-old SPF Wistar male rats were selected to construct diabetic nephropathy model rats (DN) group by continuous high-fat feeding for 4 weeks, followed by a tail vein injection of 30 mg/kg streptozotocin for 1 week. The experimental rats were divided into six groups of 10 rats: normal (control), DN, DN + ZY, DN + metformin, DN + metformin + ZY, and DN + metformin + captopril (positive control) groups. Among the groups, 6.25 g/kg ZY, 250 mg/kg metformin, and 17.5 mg/kg captopril were given to the rats by gavage once a day for 16 weeks. Blood glucose, dietary behaviour, biochemical indicators, and gene expression changes were measured in each group. RESULTS: Metformin + ZY treatment significantly lowered blood glucose, water intake, urine total protein, urine albumin, urine volume, serum triglyceride, and serum cholesterol levels in the DN group. The pathological changes of kidney tissue showed that the DN + metformin + ZY group had a protective effect on kidney tissue damage. And ZY and metformin + ZY treatments repaired the expression of genes in the DN group. DISCUSSION AND CONCLUSION: The ZY and metformin combined treatment showed a clear therapeutic effect on kidney damage in DN. This study provides a potential mechanism for the treatment of diabetic nephropathy with ZY combined with metformin.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal/pharmacology , Metformin/pharmacology , Animals , Blood Glucose/drug effects , Captopril/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Nephropathies/physiopathology , Drug Therapy, Combination , Drugs, Chinese Herbal/administration & dosage , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/pharmacology , Male , Metformin/administration & dosage , RNA, Messenger/metabolism , Rats , Rats, Wistar , Streptozocin
19.
Am J Chin Med ; 48(6): 1409-1433, 2020.
Article in English | MEDLINE | ID: mdl-32907360

ABSTRACT

Scutellaria baicalensis (SB), a herbal medicine, is commonly used to treat metabolic diseases, while Metformin (MF) is a widely used drug for type 2 diabetes. The purpose of this study was to investigate whether co-treatment of SB with MF could produce a potential therapeutic effect on high-fat and high-fructose diet (HFFD)-induced metabolic dysregulation. First, we optimized the dose of SB (100, 200, 400, and 800[Formula: see text]mg/kg) with MF (200[Formula: see text]mg/kg) in HFFD-induced C57BL6J mice. Next, the optimized dose of SB (400[Formula: see text]mg/kg) was co-administered with MF (50, 100, and 200[Formula: see text]mg/kg) in a similar animal model to find the effective combinations of SB and MF. Metabolic markers were determined in serum and tissues using different assays, histology, gene expression, and gut microbial population. The SB and MF co-treatment significantly decreased the body, liver, and VAT weights. The outcome of OGTT was improved, and the fasting insulin, HbA1c, TG, TC, LDL-c, AST, and ALT were decreased, while HDL-c was significantly increased. Histological analyses revealed maintained the integrity of liver, adipose tissue, and intestine prevented lipid accumulation in the liver and intestine and combated neuronal damage in the brain. Importantly, controlled the expression of PPAR[Formula: see text], and IL-6 genes in the liver, and expression of BDNF, Glut1, Glut3, and Glut4 genes in the brain. Treatment-specific gut microbial segregation was observed in the PCA chart. Our findings indicate that SB and MF co-treatment is an effective therapeutic approach for HFFD-induced metabolic dysregulation which is operated through the gut-liver-brain axis.


Subject(s)
Brain/metabolism , Gastrointestinal Microbiome , Liver/metabolism , Metabolic Diseases/drug therapy , Metabolic Diseases/metabolism , Metformin/administration & dosage , Metformin/pharmacology , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Animals , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Diet, Carbohydrate Loading/adverse effects , Diet, High-Fat/adverse effects , Disease Models, Animal , Drug Therapy, Combination , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Metabolic Diseases/genetics , Metabolic Diseases/microbiology , Mice, Inbred C57BL , PPAR gamma/genetics , PPAR gamma/metabolism , Scutellaria baicalensis
20.
Medicine (Baltimore) ; 99(31): e20750, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32756078

ABSTRACT

BACKGROUND: Type 2 diabetes is a kind of metabolic disease. Its clinical characteristic is hyperglycemia. Recently, more and more elderly people suffer from type 2 diabetes, and the glycemic variability of the elderly is greater. In addition, blood sugar variation is more likely to cause diabetes complications than simple hyperglycemia. Sancai podwer (SC) is based on the theory of traditional Chinese medicine and gradually formed in the summary of clinical experience. It has the effect of lowering blood sugar and alleviating clinical symptoms of diabetes. But the existing evidence of its efficacy on glycemic variability is insufficient. So, in our study, the randomized controlled trials will be used as a research method to explore the effects of SC on glycemic variability of type 2 diabetes. METHOD: We will use randomized controlled experiments based on the recommended diagnostic criteria, inclusion and exclusion criteria. A total of 60 elderly patients with type 2 diabetes will be randomly divided into treatment group and control group, 30 cases in each group. The control group will receive conventional western medicine and the intervention group will receive SC combined with western medicine. The standard deviation and coefficient of variation of blood glucose level will be used as evaluation indexes. DISCUSSION: This study can provide evidence for the clinical efficacy and safety of SC in elderly patients with type 2 diabetes mellitus. TRIAL REGISTRATION: This study is registered on the Chinese Clinical Trial Registry: ChiCTR2000032611.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/drug therapy , Drugs, Chinese Herbal/therapeutic use , Administration, Oral , Aged , Aged, 80 and over , Blood Glucose/drug effects , Drug Therapy, Combination , Drugs, Chinese Herbal/administration & dosage , Female , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Male , Metformin/administration & dosage , Metformin/therapeutic use , Powders , Randomized Controlled Trials as Topic
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