RESUMO
Grifola frondosa is an edible fungus with a variety of potential pharmacological activities. This study investigates the hypoglycemic, anti-diabetic nephritic, and antioxidant properties of G. frondosa polysaccharides in diet-streptozotocin-induced diabetic rats. After a 4-week treatment with 100 mg/kg of metformin and 200 mg/kg of one of four different G. frondosa polysaccharide mixtures (especially GFPS3 and GFPS4), diabetic rats had enhanced body weight and suppressed plasma glucose, indicating the hypoglycemic activities of the G. frondosa polysaccharides. G. frondosa polysaccharides regulated the level of serum creatinine, blood urea nitrogen, N-acetyl-ß-D-glucosaminidase, and albuminuria; inhibited the serum levels of interleukin (IL)-2, IL-6, and TNF-α; and enhanced the serum levels of matrix metalloproteinase 9 and interferon-α, confirming their anti-diabetic nephritic activities. G. frondosa polysaccharides ameliorated the pathological alterations in the kidneys of diabetic rats. Moreover, G. frondosa polysaccharides modulated the serum levels of oxidant factors such as superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, and reactive oxygen species, revealing their antioxidant properties. Furthermore, the administration of G. frondosa polysaccharides inhibited nuclear factor kappa B activities in the serum and kidneys. All of the data revealed that the activation of nuclear factor kappa B plays a central role in G. frondosa polysaccharide-mediated anti-diabetic and anti-nephritic activities.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Alimento Funcional , Grifola/metabolismo , Hipoglicemiantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Acetilglucosaminidase/metabolismo , Animais , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Catalase/sangue , Creatinina/sangue , Dieta , Dieta Hiperlipídica , Relação Dose-Resposta a Droga , Glutationa Peroxidase/sangue , Interleucina-2/sangue , Interleucina-6/sangue , Masculino , Malondialdeído/metabolismo , NF-kappa B/metabolismo , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Scutellarin (SC), mainly extracted from the Chinese herb Erigeron breviscapus (vant.), has been reported to possess various pharmacological activities; however, its effects on Alzheimer's disease (AD) have not been systemically reported. The protective effects of SC on AD were investigated using an Lglutamic acid (LGlu)damaged HT22 cell apoptosis model and an aluminum chloride plus Dgalactoseinduced AD mouse model. In LGludamaged HT22 cells, SC significantly increased cell viability, inhibited lactate dehydrogenase release, reduced caspase3 activity and suppressed apoptosis, which were determined via an MTT assay, an in vitro Toxicology Assay kit, a Caspase3 activity assay kit, and propidium iodide and Annexin V staining. Furthermore, SC suppressed the accumulation of intracellular reactive oxygen species (ROS), restored the dissipation of mitochondrial membrane potential, enhanced the expression of antiapoptotic proteins and reduced the expression of proapoptotic proteins, as determined by immunofluorescence assays and western blotting. In AD mice, SC enhanced vertical and horizontal movements in an autonomic activity test, and reduced the escape latency time in the water maze test. SC reduced the deposition of amyloid ß142 (Aß142) and the expression of phosphorylatedTau in the hippocampus as determined by immunohistochemistry analysis, but enhanced the serum levels of Aß142 of AD mice as determined by ELISA. ELISA analyses also revealed that SC enhanced the levels of acetylcholine, and superoxide dismutase in serum and brain lysate, whereas reduced the levels of ROS in brain lysate of AD mice. The present study confirmed that the protective effects of SC in AD in vitro and in vivo are associated with its antioxidant and antiapoptotic properties.
Assuntos
Doença de Alzheimer/metabolismo , Antioxidantes/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Glucuronatos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/etiologia , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores , Caspase 3/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Ácido Glutâmico/efeitos adversos , Ácido Glutâmico/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The present study successfully demonstrated the neuroprotective effects of purified Lycium barbarum polysaccharide (LBPS02) against glutamate (LGlu)induced differentiated PC12 (DPC12) cell apoptosis. Purified polysaccharide was obtained by using a diethylaminoethyl52 cellulose anion exchange column and a Sepharose G100 column. During identification and characterization, LBPS02 was validated to be a fraction with 68 kDa molecular weight, and with a structure containing 1â3, 1â4 and 1â6 linkages. Data further revealed that LBPS02 pretreatment effectively improved cell viability, reduced apoptosis rate, and restored the mitochondrial dysfunction in LGluexposed cells. LBPS02 suppressed LGluinduced reactive oxygen species (ROS accumulation in DPC12 cells. Nacetylcysteine, a ROS inhibitor, strongly enhanced the efficacy of LBPS02. Furthermore, LBPS02 normalized the levels of antiapoptotic proteins, and regulated the phosphorylation of extracellular signalregulated kinases (ERKs) and protein kinase B (Akt) in LGluexplored DPC12 cells. In conclusion, LBPS02mediated neuroprotective effects are at least partially associated with the modulation of Akt and ERKs, and the subsequent inhibition of the mitochondrial apoptotic pathway. LBPS02 may be a candidate for neurodegenerative disease treatment.
Assuntos
Ácido Glutâmico/farmacologia , Lycium/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ácido Glutâmico/toxicidade , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Zeaxanthin (ZA), an important compound found in Lycium barbarum, shows various pharmacodynamic effects. In our present study, a high-fat, high-sucrose diet and streptozotocin (STZ)-induced diabetic rat model was used to investigate the antidiabetic activities of ZA. After a 4-week administration of 200 and 400 mg/kg of ZA and 100 mg/kg of metformin hydrochloride, various blood biochemical indexes were detected. ZA strongly normalized the reduced bodyweight and enhanced fasting blood glucose in diabetic rats. The positive data obtained from the oral glucose tolerance test further confirmed its antidiabetic effects. ZA displayed significant hypolipidemic activities indicated by its modulation of serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. The antidiabetic nephropathy of ZA was confirmed by its regulation of pathological kidney structures, urine levels of n-acetyl-ß-d-glucosaminidase and albuminuria, and serum levels of urea nitrogen. ZA inhibited the serum levels of inflammatory factors including interleukin-2 (IL-2), IL-6, tumor necrosis factor-α, and nuclear factor kappa B, further confirming its renal protection. Moreover, the serum imbalances in superoxide dismutase, glutathione peroxidase, methane dicarboxylic aldehyde, and catalase were normalized by ZA, suggesting its antioxidant properties. Altogether, ZA produced hypoglycemic, hypolipidemic, and antidiabetic nephritic effects in a diet-STZ-induced diabetic rat model.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Zeaxantinas/farmacologia , Animais , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Nefropatias Diabéticas/sangue , Lipídeos/sangue , Masculino , Oxirredutases/sangue , Ratos , Ratos Sprague-DawleyRESUMO
Lycium barbarum, extensively utilized as a medicinal plant in China for years, exhibits antitumor, immunoregulative, hepatoprotective, and neuroprotective properties. The present study aims to investigate the hyperglycemic and antidiabetic nephritic effects of polysaccharide which is separated from Lycium barbarum (LBPS) in high-fat diet-streptozotocin- (STZ-) induced rat models. The reduced bodyweight and enhanced blood glucose concentration in serum were observed in diabetic rats, and they were significantly normalized to the healthy level by 100 mg/kg of metformin (Met) and LBPS at doses of 100, 250, and 500 mg/kg. LBPS inhibited albuminuria and blood urea nitrogen concentration and serum levels of inflammatory factors including IL-2, IL-6, TNF-α, IFN-α, MCP-1, and ICAM-1 compared with diabetic rats, and it indicates the protection on renal damage. Furthermore, the activities of SOD and GSH-Px in serum were enhanced strikingly by LBPS which suggests its antioxidation effects. LBPS, compared with nontreated diabetic rats, inhibited the expression of phosphor-nuclear factors kappa B (NF-κB) and inhibitor kappa B alpha in kidney tissues. Collectively, LBPS possesses antidiabetic and antinephritic effects related to NF-κB-mediated antioxidant and antiinflammatory activities.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/imunologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , NF-kappa B/imunologia , Animais , Anti-Inflamatórios/administração & dosagem , Glicemia/imunologia , Citocinas/sangue , Diabetes Mellitus Experimental/diagnóstico , Nefropatias Diabéticas/diagnóstico , Gorduras na Dieta , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Metformina/administração & dosagem , Ratos , Ratos Sprague-Dawley , Fármacos Renais/administração & dosagem , Estreptozocina , Resultado do Tratamento , Ureia/sangueRESUMO
OBJECTIVE: Hypertension is a public health problem in the world, and the disability and mortality rate is extremely high. Its important pathology foundation is vascular remodeling. Water-soluble chitosan (WSC) is the degradation product of chitosan, and have a role to control hypertension. The present study aims to investigate the regulatory effects of WSC on vascular remodeling in hypertension, and further to confirm the roles of nuclear factor c1 of activatied T cells (NFATc1) during this effect. METHODS: Primary cultured rat abdominal aortic smooth muscle cells were incubated with PBS, AngII, and AngÐÐ + WSC (0.1 mg/L) for 24 h. MTT and western blot methods were applied to analyzed the cell proliferation and c-myc protein expression, respectively, among all experimental groups. Successfully established spontaneously hypertensive Wistar-kyoto rats (SHR) were divided into two groups randomly: SHR group (n = 30) and SHR + WSC group (n = 30,WSC150 mg/kg/d). Another 15 Wistar-kyoto rats treated with PBS were served as control group. At the end of the experiments, the hemodynamic changes were analyzed using rat tail arterial pressure measuring instrument. H&E staining was performed to observe the morphological changes of abdominal aorta. Furthermore, immunohistochemical method, western blot and real-time quantitative PCR were applied to detected the expression of NAFTc1 protein and mRNA. RESULTS: WSC significantly reduced the cell viability in primary cultured rat abdominal aortic smooth muscle cells compare with PBS and AngÐÐ-treated cells. Compared with PBS group, the enhanced expression level of c-myc protein was observed in AngÐÐ-treated cells, which was significantly blocked by WSC incubation. Compared with control rats, the abnormally high blood pressure and membrane thickness/lumen diameter ratio of abdominal aorta were noted in SHR model rats, which strongly reduced after WSC administration. Hypertension resulted in an increment on expression of both NFATc1 protein and mRNA in abdominal aorta of Wistar-kyoto rats compared with control groups. Encouragingly, WSC strikingly suppressed the high levels of NFATc1 protein and even mRNA. CONCLUSION: In both cell and animal experiments, we succefully confirmed the regulatory effects of WSC on vascular remodeling in hypertension. Based on the present results, WSC-inhibited vascular remodeling may be related to the modulation on NFATc1 expression. Our experiment provides a solid basis for the clinical application of WSC on hypertension.