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BACKGROUND: Herbal medicines have been used for the preparation of numerous pharmaceutical products for the treatment of human disorders. Plant-derived products have been used in medicine, nutraceuticals, perfumery, beverages, and cosmetics industries for different purposes. Herbal medicines are mainly derived from different parts of plant materials. Phellodendron bark has been widely known as one of the fundamental herbs of traditional Chinese medicine. Phellodendron bark contains phellodendrine as a main active phytochemical. Phellodendrine ((7S,13aS)-3,10-dimethoxy-7-methyl-6,8,13,13atetrahydro-5H-isoquinolino[2,1-b]isoquinolin-7-ium-2,11-diol), is a quaternary ammonium alkaloid. METHODS: This present study aimed to investigate the biological potential and therapeutic effectiveness of phellodendrine in medicine through scientific data analysis of different research works on phellodendrine. The therapeutic value of phellodendrine was analyzed in the present work through scientific data available in Google, Google Scholar, ScienceDirect, and PubMed. All the scientific data on phellodendrine were collected from these databases using the terms herbal drugs and phellodendrine. Pharmacological and analytical data of phellodendrine were analyzed in the present work in order to know the medicinal importance of phellodendrine. RESULTS: Scientific data analysis of phellodendrine in the present work signified the biological importance of phellodendrine in medicine. Phellodendrine has numerous beneficial aspects in medicine due to its potential benefits in ulcerative colitis, inflammation, pancreatic cancer, nephritis, immune response, acetylcholinesterase activity, psoriasis, arthritis, atopic dermatitis, and oxidative stress. However, it also has significant effects on eicosanoid generation, neuraminidase-1, inflammasome generation, cytochrome p450, taste receptors, and hepatic gluconeogenesis. Furthermore, scientific data has indicated the presence of phellodendrine in different natural sources, including Phellodendri cortex. Analytical data on phellodendrines has signified their importance in the isolation and separation of pure phytochemicals in medicine. Pharmacokinetic parameters have highlighted the tissue distribution of phellodendrine in different tissue of human beings and higher animals. CONCLUSION: In the present work, scientific data analysis has indicated the biological importance, pharmacological activities, and analytical aspects of phellodendrine in medicine.
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Physical exercise is essential for the amelioration of insulin resistance (IR). The mechanisms in charge of improved IR, regulated by exercise, are insufficiently studied. Previous research revealed that Sirtuin 6 (SIRT6) - mediated insulin signaling acts a crucial element in hepatic IR. The objective of our research was to determine the effects of exercise on SIRT6-mediated insulin signaling in liver of IR rats. Forty male Sprague Dawley rats were randomly assigned to four groups (n = 10 rats each): control rats fed with standard chow (Lean group); sedentary rats fed with a high-fat diet (HFD-SED); rats fed with HFD and submitted to 8 week chronic swimming exercise training (HFD-CE); and rats fed HFD and submitted to one acute swimming exercise training (HFD-AE). HFD feeding lead to increased body weight, accumulation of hepatic triglyceride and serum free fatty acids, and enhanced gluconeogenesis. Besides, HFD feeding decreased body insulin sensitivity. Hepatic USP10 and SIRT6 protein levels decreased under obese status. Both chronic and acute exercise intervention alleviated physiological and metabolic status, increased hepatic USP10 and SIRT6 levels, improved insulin signaling transduction, and inhibited gluconeogenesis. These results showed that exercise intervention regulated SIRT6-mediated insulin signaling, which contributes to our understanding of the molecular mechanisms behind IR, in that a regular exercise can mitigate the effects of IR.
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Resistencia a la Insulina , Obesidad , Animales , Masculino , RatasRESUMEN
The glycolytic pathway of the enteric pathogen Campylobacter jejuni is incomplete; the absence of phosphofructokinase means that the suppression of futile cycling at this point in the glycolytic-gluconeogenic pathway might not be required, and therefore the mechanism for controlling pathway flux is likely to be quite different or absent. In this study, the characteristics of fructose-1,6-bisphosphatase (FBPase) of C.jejuni are described and the regulation of this enzyme is compared with the equivalent enzymes from organisms capable of glycolysis. The enzyme is insensitive to AMP inhibition, unlike other type I FBPases. Campylobacterjejuni FBPase also shows limited sensitivity to other glycolytic and gluconeogenic intermediates. The allosteric cooperative control of the enzyme's activity found in type I FBPases appears to have been lost.
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Campylobacter jejuni/enzimología , Fructosa-Bifosfatasa/metabolismo , Fructosa/metabolismo , Campylobacter jejuni/aislamiento & purificación , Campylobacter jejuni/patogenicidad , Gluconeogénesis , Glucólisis , Cinética , Modelos Biológicos , Elementos Estructurales de las ProteínasRESUMEN
The glucose intolerance developed during pregnancy is called gestational diabetes mellitus (GDM). GDM has become a severe risk for the health of both mother and baby. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus and has been reported to have anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. C57BL/KsJ-Lepdb/+ female mice were used as the GDM model. The mRNA levels of relative genes in this research were detected by quantitative real-time PCR. The protein levels of relative genes were analyzed by Western blot. Serum lipid level was measured with an ILab Chemistry Analyzer 300 PLUS. Glucose, insulin, and lipid profile levels in the GDM mice model were decreased by AS-IV treatment. AS-IV downregulated the expression of inflammatory genes and upregulated the expressions of anti-oxidant genes in the GDM mice model. AS-IV treatment reduced cAMP accumulation in liver and reduced hepatic gluconeogenesis in GDM mice. This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in a mice model through the regulation of cAMP accumulation and hepatic gluconeogenesis.
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Diabetes Gestacional/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Gluconeogénesis/efectos de los fármacos , Hipoglucemiantes/farmacología , Saponinas/farmacología , Triterpenos/farmacología , Administración Oral , Animales , Glucemia/análisis , Glucemia/metabolismo , AMP Cíclico/análisis , AMP Cíclico/metabolismo , Diabetes Gestacional/sangre , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Gluconeogénesis/genética , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Insulina/metabolismo , Leptina/genética , Lípidos/sangre , Hígado/efectos de los fármacos , Hígado/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Ratones , Ratones Transgénicos , Embarazo , Saponinas/uso terapéutico , Triterpenos/uso terapéuticoRESUMEN
Nutritional recovery of early malnutrition with a soybean diet reduces liver glycogen stores in the fed state and produces liver insulin resistance. We investigated whether nutritional recovery on a soybean flour diet alters hepatic gluconeogenesis in the adult offspring of rats deprived of protein during pregnancy and lactation. Male rats from mothers that were fed either 17% (C) or 6% (L) protein during pregnancy and lactation were maintained on a 17% casein (CC, n = 16 and LC, n = 17), 17% soybean flour (CS, n = 10 and LS, n = 10), or 6% casein (LL, n = 10) diet after weaning. The soybean diet reduced basal serum glucose (soybean diet, 5.6 ± 0.6 mmol/L vs. casein diet, 6.2 ± 0.6 mmol/L; p < 0.05) but increased alanine aminotransferase mRNA/GAPDH (soybean diet, 0.062 ± 0.038 vs. casein diet, 0.024 ± 0.011; p < 0.01), phosphoenolpyruvate carboxykinase mRNA/GAPDH (soybean diet, 1.53 ± 0.52 vs. casein diet, 0.95 ± 0.43; p < 0.05), and glycerokinase protein content (soybean diet, 0.86 ± 0.08 vs. casein diet, 0.75 ± 0.11; p < 0.05). The serum glucose concentration (recovered groups, 5.6 ± 0.5 mmol/L vs. control groups, 6.2 ± 0.7 mmol/L; p < 0.05) and phosphoenolpyruvate carboxykinase activity (recovered groups, 2.8 ± 0.6 µU/mg vs. control groups, 3.6 ± 0.6 µU/mg; p < 0.05) were decreased in rats subjected to protein restriction in early life. The glucose area under the curve during the pyruvate tolerance test did not differ among groups, whereas glucose area under the curve after glucagon infusion was reduced by early malnutrition (recovered groups, 4210 ± 572 mg/dL·40 min vs. control groups, 4493 ± 688 mg/dL·40 min; p < 0.001) and by the soybean diet (soybean diet, 3995 ± 500 mg/dL·40 min vs. casein diet, 4686 ± 576 mg/dL·40 min; p < 0.05). Thus, the soybean diet impaired the response to glucagon but did not alter gluconeogenesis.
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Alimentación Animal , Glucagón/metabolismo , Gluconeogénesis , Glycine max/metabolismo , Hígado/metabolismo , Efectos Tardíos de la Exposición Prenatal , Desnutrición Proteico-Calórica/dietoterapia , Factores de Edad , Animales , Dieta con Restricción de Proteínas , Modelos Animales de Enfermedad , Femenino , Regulación Enzimológica de la Expresión Génica , Gluconeogénesis/genética , Lactancia , Hígado/enzimología , Masculino , Estado Nutricional , Embarazo , Fenómenos Fisiologicos de la Nutrición Prenatal , Desnutrición Proteico-Calórica/genética , Desnutrición Proteico-Calórica/metabolismo , Desnutrición Proteico-Calórica/fisiopatología , Ratas WistarRESUMEN
In this study, we explored the effect of aqueous extract of leaves of Aegle marmelos (AM) on hepatic carbohydrate metabolism and insulin downstream signalling in rats given fructose (15%) in drinking water from weaning to adulthood. Wistar albino rats (4 weeks old) were randomly divided into normal control (NC), fructose control (FC), and treatment (AMT) groups and were fed for a period of 8 weeks the following diets: chow + water, chow + fructose (15%), and chow + fructose (15%) + AM (500 mg/kg per day, p.o.), respectively. Compared with the NC group, the FC group was found to have significantly (p < 0.05) raised levels of fasting blood glucose, lipid, visceral mass, plasma insulin and leptin, glycogen, and gluconeogenesis enzyme but decreased glycolytic enzyme activity. Raised levels of glucose transporter 2 protein but decreased activity of phosphatidylinositol-3-kinase (PI3K/Akt) and Janus kinase - signal transducer and activator of transcription-3 (JAK-STAT3) in hepatic tissue indicate a state of insulin and leptin resistance in the FC group. A significant (p < 0.05) lowering of physical and glycemic parameters, strengthening of the hepatic glycolytic pathway over the gluconeogenic pathway, and upregulation of the PI3K/Akt and JAK-STAT3 pathways was observed in the AMT group, as compared with the FC group. For the first time, the mechanism underlying the development of insulin resistance syndrome is delineated here, along with the potential of A. marmelos to impede it.
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Aegle/química , Ingestión de Líquidos , Fructosa/administración & dosificación , Resistencia a la Insulina , Extractos Vegetales/farmacología , Destete , Animales , Glucemia/metabolismo , Ayuno/sangre , Transportador de Glucosa de Tipo 2/metabolismo , Crecimiento y Desarrollo/efectos de los fármacos , Insulina/metabolismo , Leptina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Ratas , Ratas Wistar , Rutina/análisis , Transducción de Señal/efectos de los fármacosRESUMEN
Ferulic acid (FA) is a phenolic phytochemical known for its antidiabetic property The present study is designed to evaluate the mechanism behind its antidiabetic property in high-fat and fructose-induced type 2 diabetic adult male rats. Animals were divided into 5 groups: (i) control, (ii) diabetic control, (iii) diabetic animals treated with FA (50 mg/(kg body weight · day)(-1), orally) for 30 days, (iv) diabetic animals treated with metformin (50 mg/(kg body weight · day)(-1), orally) for 30 days, and (v) control rats treated with FA. FA treatment to diabetic animals restored blood glucose, serum insulin, glucose tolerance, and insulin tolerance to normal range. Hepatic glycogen concentration, activity of glycogen synthase, and glucokinase were significantly decreased, whereas activity of glycogen phosphorylase and enzymes of gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)) were increased in diabetic animals and FA restored these to normal levels similar to that of metformin. FA improved the insulin signalling molecules and reduced the negative regulators of insulin signalling. The messenger RNA of gluconeogenic enzyme genes (PEPCK and G6Pase) and the interaction between forkhead transcription factor-O1 and promoters of gluconeogenic enzyme genes (PEPCK and G6Pase) was reduced significantly by ferulic acid. It is concluded from the present study that FA treatment to type 2 diabetic rats improves insulin sensitivity and hepatic glycogenesis but inhibits gluconeogenesis and negative regulators of insulin signalling to maintain normal glucose homeostasis.
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Ácidos Cumáricos/farmacología , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Tipo 2/sangre , Insulina/sangre , Hígado/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Colagogos y Coleréticos/sangre , Colagogos y Coleréticos/farmacología , Ácidos Cumáricos/sangre , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Fructosa , Gluconeogénesis/efectos de los fármacos , Hipoglucemiantes/sangre , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Hígado/efectos de los fármacos , Masculino , RatasRESUMEN
The our objective was to investigate the adaptations induced by a low-protein, high-carbohydrate (LPHC) diet in growing rats, which by comparison with the rats fed a control (C) diet at displayed lower fasting glycemia and similar fasting insulinemia, despite impairment in insulin signaling in adipose tissues. In the insulin tolerance test the LPHC rats showed higher rates of glucose disappearance (30%) and higher tolerance to overload of glucose than C rats. The glucose uptake by the soleus muscle, evaluated in vivo by administration of 2-deoxy-[(14)C]glucose, increased by 81%. The phosphoenolpyruvate carboxykinase content and the incorporation of [1-(14)C]pyruvate into glucose was also higher in the slices of liver from the LPHC rats than in those from C rats. The LPHC rats showed increases in l-lactate as well as in other gluconeogenic precursors in the blood. These rats also had a higher hepatic production of glucose, evaluated by in situ perfusion. The data obtained indicate that the main substrates for gluconeogenesis in the LPHC rats are l-lactate and glycerol. Thus, we concluded that the fasting glycemia in the LPHC animals was maintained mainly by increases in the hepatic gluconeogenesis from glycerol and l-lactate, compensating, at least in part, for the higher glucose uptake by the tissues.
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Glucemia/metabolismo , Dieta con Restricción de Proteínas , Carbohidratos de la Dieta/administración & dosificación , Ayuno/sangre , Gluconeogénesis , Glucosa/biosíntesis , Hígado/metabolismo , Tejido Adiposo/metabolismo , Animales , Prueba de Tolerancia a la Glucosa , Glicerol/sangre , Insulina/sangre , Ácido Láctico/sangre , Masculino , Músculo Esquelético/metabolismo , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , RatasRESUMEN
Cancer cachexia is a metabolic syndrome featuring many alterations typical of type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia, epidemiological evidence also supports an accelerated age-related muscle loss in T2D. Insulin resistance manifests in both conditions and impairs glucose disposal and protein anabolism by tissues. A greater contribution of gluconeogenesis to glucose production may limit amino acid availability for muscle protein synthesis, further aggravating muscle loss. In the context of inter-dependence between glucose and protein metabolism, the present review summarizes the current state of knowledge on alterations that may lead to muscle wasting in human cancer. By highlighting the similarities with T2D, a disease that has been more extensively studied, the objective of this review is to provide a better understanding of the pathophysiology of cancer cachexia and to consider potential treatments usually targeted for T2D. Nutritional approaches aimed at stimulating protein anabolism might include specially formulated food with optimal protein and amino acid composition. Because the gradual muscle loss in T2D may be attenuated by diabetes treatment, anti-diabetic drugs might be considered in cachexia treatment. Metformin emerges as a choice candidate as it acts both on reducing gluconeogenesis and improving insulin sensitivity, and has demonstrated tumour suppressor properties in multiple cancer types. Such a multimodal approach to slow or reverse muscle wasting in cachexia warrants further investigation.