The effects of puerarin on electroretinogram, oxidative stress and STAT3 expression were determined, in diabetic rat retina and serum. Forty Sprague-Dawley rats were randomly divided into the normal control (NC), the diabetic model (DM), the low dose (250 mg/kg) puerarin (LP) or the high dose (500 mg/kg) puerarin group (HP). A diabetic rat model was induced by streptozotocin and animals were continuously treated for 4 weeks; fasting blood glucose was measured at 2 and 4 weeks after modeling. An electroretinogram and serum and tissue levels of glucose, insulin, superoxide dismutase (SOD), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) were measured; real-time PCR and ELISA were used to determine STAT3 mRNA and protein expression, respectively, from the retina. The blood glucose and insulin levels in the puerarin groups were significantly lower and higher, respectively than that in the DM group. The amplitude of b-wave of electroretinogram in the DM and the LP groups was significantly lower than that in the NC group; in the LP and HP groups it was significantly higher than the DM group. The serum and retinal tissue activity of SOD and MDA was significantly lower and higher, respectively, in the DM group compared to the NC group; both the LP and HP groups had significantly higher SOD and lower MDA than the DM group. The levels of STAT3 mRNA and protein levels in the DM, LP and HP groups were significantly higher than the NC group; and levels of STAT3 mRNA and protein expression were significantly lower in the LP and HP groups than the DM group. In summary, puerarin can reduce the oxidative stress damage of the retina, and its mechanism is related to the inhibition of STAT3 expression.
ObjectiveB6, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aimed to explore the efficacy of B6 on diabetic nephropathy and the related mechanisms.Materials and methodsThe effects of B6 were studied on fast-blood glucose, serum creatinine, urea nitrogen, urine albumen/24 h, pathological changes of main organs, the levels of ACE2 and ACE2 mRNA in the rat model of diabetes induced by streptozotocin.ResultsThe results showed that B6 treatment could reduce serum creatinine, urea nitrogen, urine albumen/24 h, decrease the level of AngII, improve the renal pathological changes in diabetic rats and increase the levels of ACE2 and ACE2 mRNA.ConclusionThese results suggested B6 could protect the renal function of diabetic rats. This study provided scientific basis for the further researches and clinical applications of B6.
The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3′ may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.Key words xanthine derivative; monoamine oxidase B inhibition activity; substituent effect Parkinson's disease (PD) is a neurodegenerative disorder characterized pathologically by a marked loss of dopaminergic nigrostriatal neurons and clinically by disabling movement disorders.1) Currently, the therapy of PD is largely focused on dopamine replacement strategies with the dopamine precursor levodopa and dopamine agonist drugs. Although these strategies are highly effective in controlling the disease at the early stages, drug-related complications are associated with long-term treatment. The inadequacies of dopamine replacement therapy have prompted the research of alternative drug targets. 2-5)Monoamine oxidase (MAO) is an integral protein of the outer mitochondrial membrane, and exist in two forms, namely, monoamine oxidase A (MAO-A) and MAO-B. MAO-A preferentially deaminates aromatic monoamines such as the neurotransmitters serotonin (5-HT), noradrenaline (NA), andadrenaline (A); MAO-B is one of the most important key enzymes in metabolic pathways in vivo and plays mainly three roles: firstly, MAO-B decomposes dopamine into 3,4-dihydroxyphenyl acetic acid and homovanillic acid, meanwhile producing the neurotoxic H 2 O 2 . Secondly, MAO-B inactivates p-phenylethylamine which has the ability to stimulate secrection and reuptake function of dopamine. Thirdly, in the precence of MAO-B, catalyzed oxidation of 1-methyl-4-phenyl-1,2,3,6-terahydropyridine (MPTP) to intermediate 1-methyl-4-phenyl-2,3-dihydropyridin-1-ium (MPDP + ) and then to 1-methyl-4-phenylpyridin-1-ium (MPP + )with neurotoxicity occurs. Together these suggest that inhibiting the action of MAO-B can not only reduce the degradation of dopamine and reuptake, improving the concentration of dopamine in the brain, but also lower levels of H 2 O 2 , and MPP + to enhance neuroprotective properties. [6][7][8][9][10][11][12] Recently, xanthine and its derivatives were reported to produce little or no inhibition of MAO-B. In the last decade, when introducing phenyl at position-8, 8-phenyl xanthine exhibited MAO-B inhibition activity in vitro with a inhibition constant (K i ) value of 86.2 μM.2) Petzer et al. found a series of 8-styryl xanthine analogues exhibiting more powerful inhibition of MAO-B than 8-phenyl xanthine analogues (CSC K i =100 nM; KW6...
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