RESUMO
Six new cytochalasans-namely, aspergicytochalasins A-F (1-6)-together with five known analogs were isolated and characterized from the endophytic fungus Aspergillus sp. from the medicinal plant Lonicera japonica. The structures of the new compounds were established by NMR and MS methods as well as single crystal X-ray diffractions. Compounds 3 and 4 showed weak antibacterial activities to Staphylococcus aureus, with MIC values of 128 and 64 µg/mL, respectively. Compounds 1, 3, 5 and 6 showed inhibitory activities on NO production, with IC50 values less than 40 µM.
RESUMO
The mechanism underlying epithelialtomesenchymal transition (EMT) caused by high glucose (HG) stimulation in diabetic nephropathy (DN) remains to be fully elucidated. The present study investigated the effects of HG on EMT and the activity of glycogen synthase kinase 3ß (GSK3ß) in podocytes and the kidneys of db/db mice, and assessed the effects of (2'Z, 3'E)6bromoindirubin3'oxime (BIO), an inhibitor of GSK3ß, on EMT and glomerular injury. The resulting data showed that the activity of GSK3ß was upregulated by HG and downregulated by BIO in the podocytes and the renal cortex. The expression levels of epithelial markers, including nephrin, podocin and synaptopodin, were decreased by HG and increased by BIO, whereas the reverse were true for mesenchymal markers, including αsmooth muscle actin (αSMA) and fibronectin. The expression levels of ßcatenin and Snail, in contrast to current understanding of the Wnt signaling pathway, were increased by HG and decreased by BIO. In addition, expression of the vitamin D receptor (VDR) was decreased by HG and increased by BIO. In conclusion, the present study revealed that the mechanism by which BIO inhibited HGmediated EMT in podocytes and the renal cortex was primarily due to the VDR. Treatment with BIO protected renal function by maintaining the integrity of the filtration membrane and decreasing UAE, but not by regulating blood glucose. Therefore, GSK3ß may be used as a sensitive biomarker of DN, and its inhibition by BIO may be effective in the treatment of DN.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Proteinúria , Animais , Biomarcadores , Glicemia/efeitos dos fármacos , Peso Corporal , Linhagem Celular Transformada , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/urina , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/ultraestrutura , Masculino , Camundongos , Podócitos/ultraestruturaRESUMO
In this study, the antioxidant activities of 15 flavonoids against lard oil oxidation were determined by using the Rancimat test. Quercetin, dihydromyricetin, luteolin and kaempferol showed the strongest antioxidant activity, with protection factor values (PF) of 11.50, 11.29, 4.24 and 2.49, respectively. The role of conjugated hydroxyl groups of the B and C ring is discussed. By using the following descriptors: DeltaH(f) (the difference in heat of formation between flavonoids and their free radicals resulted after hydrogen atom donation) and H(BC) (the number of conjugated hydroxyl groups of the B and C ring), the result obtained in the antioxidant Rancimat test could be successfully explained.