RESUMO
Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus. To mimic the hyperglycemic conditions in DN patients, we used high glucose (25[Formula: see text]mmol/L) media to stimulate mouse mesangial cells (MMCs), and EASM inhibited high glucose-induced reactive oxygen species. We also observed that EASM enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), which mediated the anti-oxidant response, and its downstream gene heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) with concomitant decrease of expression of kelch-like ECH-associated protein 1 (keap1) both in vitro and in vivo. Taken together, these results suggest that EASM alleviates the progression of DN and this might be associated with activation of Nrf2.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Salvia miltiorrhiza/química , Acetatos , Animais , Células Cultivadas , Diabetes Mellitus Experimental , Nefropatias Diabéticas/genética , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células Mesangiais , Camundongos , Camundongos Endogâmicos C57BL , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , EstreptozocinaRESUMO
Si-Miao-Wan (SMW), a tradiational Chinese medicinal formula consisting of Atractylodis Rhizoma, Phellodendri Chinensis Cortex, Coicis Semen, and Achyranthis Bidentatae Radix, has been used for the treatment of gout and gouty arthritis for many years. In the present study, a liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) method was established to identify the multiple constituents of SMW and its metabolites in rat biological samples after oral administration. A total of 48 compounds in SMW, including 21 alkaloids, 12 organic acids, 2 terpenes, 3 lactones, 2 phytosterols, and 8 other compounds, were tentatively characterized with the diagnostic-ion filtering strategy. Based on the diagnostic ions applied to identify compounds in SMW, 28 prototype compounds and 10 metabolic compounds were detected in the biological samples. This was the first comprehensive drug metabolism investigation of SMW in rats. The developed method could be a useful means for identifying the multi-components in SMW and the metabolic components. The results may help explore the possible metabolic processes and mechanism of action for SMW in vivo.
Assuntos
Alcaloides/química , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas em Tandem/métodos , Alcaloides/administração & dosagem , Alcaloides/metabolismo , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
In this paper, submersed plant Hydrilla verticillata was cultivated in a 1/10 Hoagland culture medium added with different concentration NH4 + -N (0, 0. 5, 2. 0, 4. 0 mg x L(-1)) and 10 mg x L(-1) cadmium to study the effects of NH4 + -N on H. verticillata growth and its antioxidant enzyme system under Cd stress, and approach the degradation mechanism of submersed macrophyte in eutrophic and polluted water bodies. The results showed that under 10 mg x L(-1) Cd stress, the chlorophyll content of H. verticillata decreased obviously, and SOD and POD activities increased first but declined then. NH4 + -N accelerated the stress effect of Cd. Under 0. 5 h joint stress of Cd and NH4 + -N, SOD activity increased significantly, while such an increase needed 3 hours under single Cd stress. Relative to chlorophyll and protein, antioxidant enzyme system was an early sensitive index, and SOD was more sensitive than POD. After two days exposure to Cd plus NH4 -N, H. verticillata was mainly stressed by Cd, and NH4+ -N stress could be neglected.