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1.
Int J Med Mushrooms ; 22(7): 683-692, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32865925

RESUMEN

Nonalcoholic steatohepatitis (NASH) is becoming the most common cause of hepatocellular carcinoma (HCC). Natural products including edible mushrooms are gaining attention for the prevention and treatment of lifestyle related disorders. Ceraceomyces tessulatus (strain BDM-X) possesses potent antioxidative stress activity. In this study, we hypothesize that BDM-X treatment protects the liver of mouse with NASH by reducing inflammation in a novel NASH-HCC mouse model. C57BL/6J female pups were exposed to low-dose streptozotocin (STZ) and fed a high-fat diet (HFD) 32 from the age of 4 weeks to 16 weeks. Water extract of BDM-X was given at 500 mg/kg dose daily by oral gavage started at the age of 12 weeks and continued until 16 weeks of age along with HFD feeding. We found that BDM-X improved the histopathological changes, serum aminotransferases, and blood glucose levels in NASH mice. The hepatic protein expressions of SIRT1 and IL-10 were significantly repressed in NASH mice. BDM-X treatment restored these expressions. BDM-X treatment effectively reduced the progression of NASH by suppressing the protein expression of SREBPlc, p-NF-κB, Ep-CAM, and prothrombin in the NASH liver. In conclusion, our data suggest that BDM-X can protect the liver against inflammation and lipogenesis in NASH-HCC mice.


Asunto(s)
Basidiomycota , Productos Biológicos/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/terapia , Animales , Femenino , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Sustancias Protectoras/uso terapéutico
2.
Int Immunopharmacol ; 49: 161-167, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28595079

RESUMEN

Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFα, IL-1ß, IFNγ). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Curcumina/uso terapéutico , Riñón/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Apoptosis , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Dieta Alta en Grasa , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Riñón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , NADPH Oxidasas/metabolismo , Transducción de Señal , Estreptozocina/administración & dosificación
3.
Nutrition ; 34: 47-54, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28063511

RESUMEN

Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics.


Asunto(s)
Curcumina/farmacocinética , Cardiomiopatías Diabéticas/tratamiento farmacológico , Hipoglucemiantes/farmacocinética , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Antioxidantes/administración & dosificación , Antioxidantes/farmacocinética , Curcuma/química , Curcumina/administración & dosificación , Curcumina/química , Modelos Animales de Enfermedad , Corazón/efectos de los fármacos , Corazón/fisiología , Humanos , Hipoglucemiantes/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacocinética
4.
Int Immunopharmacol ; 44: 174-182, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28110063

RESUMEN

Curcumin, a phenolic compound, has a wide spectrum of therapeutic effects such as antitumor, anti-inflammatory, anti-cancer and so on. The study aimed to investigate the underlying mechanisms of curcumin to protect liver damage and progression of non-alcoholic steatohepatitis (NASH) in a novel NASH-hepatocellular carcinoma (HCC) mouse model. To induce this model neonatal C57BL/6J male mice were exposed to low-dose streptozotocin and were fed a high-fat diet (HFD) from the age of 4weeks to 14weeks. Curcumin was given at 100mg/kg dose daily by oral gavage started at the age of 10weeks and continued until 14weeks along with HFD feeding. We found that curcumin improved the histopathological changes of the NASH liver via reducing the level of steatosis, fibrosis associated with decreasing serum aminotransferases. In addition, curcumin treatment markedly reduced the hepatic protein expression of oxidative stress, pro-inflammatory cytokines, and chemokines including interferon (IFN) γ, interleukin-1ß and IFNγ-inducible protein 10, in NASH mice. Furthermore, curcumin treatment significantly reduced the cytoplasmic translocation of high mobility group box 1 (HMGB1) and the protein expression of toll like receptor 4. Nuclear translocation of nuclear factor kappa B (NF-κB) was also dramatically attenuated by the curcumin in NASH liver. Curcumin treatment effectively reduced the progression of NASH to HCC by suppressing the protein expression of glypican-3, vascular endothelial growth factor, and prothrombin in the NASH liver. Our data suggest that curcumin reduces the progression of NASH and liver damage, which may act via inhibiting HMGB1-NF-κB translocation.


Asunto(s)
Carcinoma Hepatocelular/prevención & control , Curcumina/uso terapéutico , Proteína HMGB1/metabolismo , Neoplasias Hepáticas/prevención & control , Hígado/efectos de los fármacos , FN-kappa B/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Transporte Activo de Núcleo Celular/efectos de los fármacos , Animales , Animales Recién Nacidos , Carcinoma Hepatocelular/etiología , Modelos Animales de Enfermedad , Fibrosis , Humanos , Hígado/patología , Neoplasias Hepáticas/etiología , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estrés Oxidativo/efectos de los fármacos , Estreptozocina
5.
Life Sci ; 153: 118-23, 2016 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-27084528

RESUMEN

AIMS: Sustained glucagon infusion increases hepatic glucose production, but this effect is transient due to hypothalamic glucagon signaling. In hypoglycemia, glucagon acts as a major defense to sustain the blood glucose level and this raises the question regarding glucagon signaling associated glucose production in prolonged fasting hypoglycemia. In this study, we investigated the proteins associated with hypothalamic glucagon signaling and liver gluconeogenesis during fasting hypoglycemia. MAIN METHODS: 8-9week old, male C57BL6/J mice were fasted for 4, 8, 12, 18, 24, 30, 36 or 42h. In the hypothalamus, we investigated glucagon signaling by analyzing the glucagon receptor and its downstream protein, peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1) expression. In the liver, we investigated gluconeogenesis by analyzing p-protein kinase A (PKA)(Ser/Thr) substrate and phosphoenolpyruvate carboxykinase - cytosolic (PEPCK-C) expression using the western blotting technique. KEY FINDINGS: The elevated or trended higher hypothalamic glucagon receptor and PGC-1 expressions at 18 and 42h were correlated with the attenuated liver p-PKA(Ser/Thr) substrate expression. The attenuated hypothalamic glucagon receptor and PGC-1 expressions at 12, 24, 30 and 36h were correlated with the elevated or trended higher liver p-PKA(Ser/Thr) substrate expression. SIGNIFICANCE: The hypothalamic glucagon signaling during fasting hypoglycemia might have been modulated by circadian rhythm and this possibly attenuates the liver p-PKA(Ser/Thr) substrate to modify the gluconeogenesis pathway. This mechanism will help to understand the hyperglucagonemia associated complications in diabetes.


Asunto(s)
Glucagón/metabolismo , Hipoglucemia/metabolismo , Hipotálamo/metabolismo , Transducción de Señal , Animales , Glucemia/metabolismo , Peso Corporal , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos C57BL , Tamaño de los Órganos , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Especificidad por Sustrato , Factores de Transcripción/metabolismo
6.
Drug Discov Today ; 21(5): 843-9, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26995272

RESUMEN

Inflammatory bowel diseases (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic ailments of the gastrointestinal tract, characterized by recurrent inflammation. Current therapeutic strategies are based on the mitigation of symptoms, including inflammatory remission and healing of mucosal manifestations. Extensive studies have suggested that continuous oxidative damage can lead to the inflammatory signaling cascade in IBD. Curcumin, a potent modulator of cell signaling, is popular for its antioxidant and anti-inflammatory activities, and has already been shown remarkable therapeutic results in IBD. Here, we review and discuss the effects of curcumin as a therapeutic agent in the chemoprevention of IBD.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Curcumina/uso terapéutico , Enfermedades Inflamatorias del Intestino/prevención & control , Quimioprevención , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/etiología
8.
Am J Chin Med ; 44(1): 87-101, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26916916

RESUMEN

Endoplasmic reticulum stress (ERS) plays a crucial role in the development of insulin resistance and diabetes mellitus. Although antidiabetic use of mulberry leaves (MLs) has been popular due to their many anti-oxidative flavonoid compounds and free radical scavenging effects, ML's effects on ERS in experimental diabetic hepatocyte injury remain unknown. To investigate how ML affect ERS in diabetic liver, Sprague-Dawley (SD) rats were assigned to induce diabetes by a single intraperitoneal injection of streptozocin (STZ; 55 mg/kg) and fed with either normal chow or a diet containing 25% mulberry leaf powder diet (MLD) and examined for 56 days. We observed that MLD improved the rats' morphological and histopathological changes. Levels of ERS markers such as phosphorylated double-stranded RNA-dependent protein kinase-like endoplasmic reticulum kinase (PERK) and X-box binding protein 1 (XBP1) and the protein expression of glucose regulated protein 78 (GRP78) were significantly higher in the diabetic liver compared to normal liver. MLD for 8 weeks significantly reduced all of these markers. MLD also significantly decreased hepatocyte apoptosis, hepatic macrophage recruitment, cellular infiltration, and CCAAT/enhancer-binding protein homologous protein (CHOP), tumor necrosis factor receptor associated factor 2 (TRAF2), interleukin 1[Formula: see text] (IL-1[Formula: see text]) and sterol regulatory element binding protein isoform 1c (SREBP 1c) levels in diabetic liver. These results may suggest that MLs can preserve hepatic function in experimental diabetes by modulating ERS mediated apoptosis and liver damage.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/dietoterapia , Estrés del Retículo Endoplásmico/fisiología , Hepatopatías/dietoterapia , Hepatopatías/etiología , Morus , Fitoterapia , Animales , Masculino , Hojas de la Planta , Ratas Sprague-Dawley , Estreptozocina
9.
Int Immunopharmacol ; 29(2): 957-963, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26548346

RESUMEN

Jumihaidokuto, a Japanese kampo medicine, is prescribed in Japan for its anti-inflammatory activity. Here we have examined its beneficial effects against acute colitis induced by dextran sulfate sodium (DSS) in mice. We have used C57BL/6 female mice, divided into two groups and received 3% DSS in drinking water during the experimental period (8days). Treatment group mice received 1g/kg/day dose of Jumihaidokuto orally whereas DSS control group received equal volume of distilled water. Normal control group mice received plain drinking water. Jumihaidokuto treatment attenuated the colitis symptoms along with suppression of various inflammatory marker proteins such as IL-1ß, IL-2Rα, IL-4, CTGF and RAGE. It has also down-regulated the oxidative stress and apoptotic signaling in the colons of mice with colitis. The present study has confirmed the beneficial effects of Jumihaidokuto on DSS induced acute colitis in mice and suggests that it can be a potential agent for the treatment of colitis.


Asunto(s)
Apoptosis/efectos de los fármacos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Enfermedad Aguda , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Degranulación de la Célula/efectos de los fármacos , Citocinas/biosíntesis , Sulfato de Dextran , Femenino , Inflamación/metabolismo , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos
10.
Int Immunopharmacol ; 29(2): 869-875, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26344429

RESUMEN

Toki-shakuyaku-san (TOKI) is a Japanese kampo medicine, which consists of a mixture of herbal medicines and considered to be a promising remedial agent due to its immunomodulatory and anti-inflammatory effects. We examined the beneficial effects of TOKI in inflammatory bowel disease associated with the inflammation of the intestinal barrier. A study was designed, using C57BL/6 female mice and were administered with 3% DSS in drinking water for 8days with or without 1g/kg/day TOKI orally for the last 3days and a normal group supplied with plain drinking water for 8days. TOKI treatment attenuated the clinical symptoms of acute murine colitis and also alleviated the inflammatory mechanism by reducing the inflammatory mediators, such as IL-1ß, IL-2, TGF-ß, RAGE and TLR2. It has also decreased the levels of CHOP, caspase12, cleaved caspase3 and cleaved caspase7 and thereby down-regulated the endoplasmic reticulum stress and apoptotic signaling induced by DSS. Moreover, the expression levels of cyclin D1 and c-kit have also confirmed the beneficial role of TOKI in colitis. All these data suggested that TOKI can be a promising agent for the treatment of colitis since it alleviates the disease progression and severity.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Colitis/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Kampo , Animales , Apoptosis/efectos de los fármacos , Colitis/inducido químicamente , Colon/patología , Citocinas/biosíntesis , Sulfato de Dextran , Estrés del Retículo Endoplásmico/efectos de los fármacos , Femenino , Mediadores de Inflamación , Ratones , Ratones Endogámicos C57BL , Pérdida de Peso/efectos de los fármacos
11.
Cytokine ; 74(2): 305-12, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25873126

RESUMEN

The renin angiotensin system (RAS) is essential for the regulation of cardiovascular and renal functions to maintain the fluid and electrolyte homeostasis. Recent studies have demonstrated a locally expressed RAS in various tissues of mammals, which is having pathophysiological roles in those organ system. Interestingly, local RAS has important role during the inflammatory bowel disease pathogenesis. Further to delineate its role and also to identify the potential effects of telmisartan, an angiotensin receptor blocker, we have used a mouse model of acute colitis induced by dextran sulphate sodium. We have used 0.01 and 5mg/kg body weight doses of telmisartan and administered as enema to facilitate the on-site action and to reduce the systemic adverse effects. Telmisartan high dose treatment significantly reduced the disease activity index score when compared with the colitis control mice. In addition, oxidative stress and endoplasmic reticulum stress markers expression were also significantly reduced when compared with the colitis control mice. Subsequent experiments were carried out to investigate some of the mechanisms underlying its anti-inflammatory effects and identified that the mRNA levels of pro-inflammatory cytokines such as tumour necrosis factor α, interleukin 1ß, interleukin 6 and monocyte chemoattractant protein 1 as well as cellular DNA damage were significantly suppressed when compared with the colitis control mice. Similarly the apoptosis marker proteins such as cleaved caspase 3 and 7 levels were down-regulated and anti-apoptotic protein Bcl2 level was significantly upregulated by telmisartan treatment. These results indicate that blockade of RAS by telmisartan can be an effective therapeutic option against acute colitis.


Asunto(s)
Bencimidazoles/farmacología , Benzoatos/farmacología , Colitis , Citocinas/inmunología , Sulfato de Dextran/toxicidad , Enfermedad Aguda , Animales , Caspasa 3/inmunología , Caspasa 7/inmunología , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/inmunología , Modelos Animales de Enfermedad , Femenino , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/inmunología , Telmisartán
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