Protective effects of carnosic acid against aging in a premature cellular senescence model and in a D-galactose induced mouse model / 药学学报

This study aimed to investigate the effect and possible mechanism of carnosic acid (CA) on delaying aging. The effects of CA on senescence-related β-galactosidase (SA-β-Gal) activity and expressions of p53, p21 and p16 were evaluated by an oxidative challenge induced premature 2BS cell senescence model. Meanwhile, the animal experiment was approved by the Ethics Committee of Zhejiang Hospital. Male C57 BL/6J mice were injected with 100 mg·kg-1·d-1 D-galactose (D-gal) for 8 weeks to establish an aging model in vivo, and CA at 5 and 10 mg·kg-1·d-1 were given ig administration at the same time. Morris water maze test was used to test the spatial memory ability. Then the serum and tissue samples were collected for the detections of malondialdehyde (MDA), total superoxide dismutase (T-SOD), interleukin-6 (IL-6), tumor necrosis factor α (TNFα) and advanced glycation end products (AGEs) as well as the protein expression of p53, p21 and p16 in hippocampus of brain. The results showed that H2O2 induced increment of SA-β-Gal activity (95%) was prevented by CA treatment (35%) and the enhanced protein expressions of p53, p21 and p16 in H2O2 exposed 2BS cells were alleviated by CA treatment, suggesting a potent protective role of CA against premature senescence induced by oxidative challenge. For in vivo study, D-gal induced declined spatial memory ability was partly reversed by CA administration. Besides, the serum and cerebral levels of MDA, IL-6, TNFα and AGEs were attenuated by CA treatment when compared to those in model mice. And the protein expressions of p53, p21 and p16 in mice hippocampus were suppressed by CA in D-gal treated mice. Taken together, our results showed that CA protects premature senescence induced by oxidative stress and D-gal, which is related to its antioxidative, antiinflammatory roles and inhibition on non-enzymatic glycosylation.

Inhibition of puerarin on formation of advanced glycation end products in vivo and in vitro / 中草药

Objective: To study the influence of puerarin on advanced glycation end products (AGEs) formation in vivo and in vitro. Methods: C57BL/6 mice were fed with high fat diet and injected with streptozotocin (40 mg/kg) to establish diabetic model. After modeling, mice were randomly divided into blank control group, model group, aminoguanidine group (100 mg/kg), low-, mid-, and high-dose puerarin (50, 100, and 200 mg/kg) groups. After treatment of eight weeks, the levels of fasting blood-glucose (FBG), oral glucose tolerance test (OGTT), glycated serum protein (GSP), and AGEs in serum were detected. To establish non-enzymatic glycation reaction model in vitro, glucose and bovine serum albumin (BSA) were incubated with puerarin at different concent rations respectively for 144 h. The productivity of non-enzymatic advanced glycation end products was detected by aspectrophotometer. Results: Puerarin can significantly lower the level of FBG and oral glucose tolerance in diabetic mice, and inhibit the productivity of GSP and AGEs in serum. Besides, puerarin also significantly inhibits the productivity of AGEs in vitro in a concentration-dependent manner. Conclusion: Puerarin possesses significant inhibitory effect on the productivity of AGEs in vivo and in vitro.

Inhibitory effects of extracts from Moutan Cortex on formation of advanced glycation end-products (AGEs) in vitro and specificity screening of its potential active components / 中国中药杂志

In this study, bovine serum albumin (BSA)/methylglyoxal (MGO) non-enzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects of Moutan Cortex extracts on the formation of AGEs. The HPLC-LC-ESI-MS/MS technology was adopted to test and indentify active components in Moutan Cortex against AGEs formation. The different concentrations of extracts (crude herb concentration 50, 100, 150, 200, 250 g•L⁻¹) from Moutan Cortexwas determined by fluorospectrophotometry, indicating an activity against AGEs formation in different concentrations of extracts, the inhibition ratio were (36.2±5.3)%, (43.5±6.2)%, (55.4±7.8)%, (68.6±6.7)%, (70.4±8.2)%, respectively after 6-day reaction in a dose dependent manner. Besides, the forming speed of AGEs tended to be steady after 24 h reaction. The HPLC technology was used to analyze chromatograms before and after the incubation of Moutan Cortex and methylglyoxal, identify changes in five chromatographic peaks and show decrease or increase in chromatographic peaks. These substances were trigalloyl glucose, tetragalloyl glucose, galloylpaeoniflorin, hexagalloyl glucose and benzoylpaeoniflorin after LC-ESI-MS/MS identification. Extracts from Moutan Cortex showed the remarkable inhibitory effects against formation of AGEs in BSA/glucose system. Furthermore, these potential active components might be associated with the efficacy of Moutan Cortex on treatment of diabetic nephropathy, which enriches basic studies for Moutan Cortex and provides ideas and reference basis for subsequent studies.

Screening for anti-diabetic effective fraction in leaves of Olea europaea / 中草药

Objective: To screen the anti-diabetic effective fraction in the leaves of Olea europaea. Methods: Different fractions (Frs. A-F) were prepared using reflux extraction and separation with macroporous resins. α-Amylase system, non-enzymatic glycation system, and alloxan-induced diabetic models of mice were used to evaluate the anti-diabetic activities of the different fractions, respectively. Results: Frs. C-F fractions showed the significant inhibitory activities against α-amylase system and non-enzymatic glycation system. Especially, fraction D showed the best anti-diabetic activity compared with the other fractions, which also displayed a good dose-effect relationship. The anti-diabetic activities of Frs. C and D were both obvious and Fr. D showed more significance. Conclusion: The leaves of O. europaea show the potential anti-diabetic activity and the most effective fraction is ascribed to Fr. D.

Glucosilación no enzimática y complicaciones crónicas de la diabetes mellitus / Non-enzymatic glycosylation and chronic complications of diabetes mellitus

La hiperglucemia es considerada hoy como un factor patogénico fundamental del desarrollo de las complicaciones neurovasculares diabéticas y, específicamente, desempeña un papel preponderante en el fenómeno de la glucosilación no enzimática y la formación de productos finales de la glucosilación avanzada. Objetivos: describir los mecanismos de la formación de los productos finales de la glucosilación avanzada y su relación con las complicaciones de la diabetes mellitus. Desarrollo: los productos finales de la glucosilación avanzada se producen por la reacción no enzimática de la glucosa y otros derivados glucados (glioxal, metilglioxal y 3-desoxiglucosona) con grupos amino de proteínas de larga vida. La glucosilación altera la estructura, las propiedades físico-químicas y la función de las proteínas intracelulares y extracelulares. En la membrana basal de los pequeños vasos se produce un engrosamiento y una distorsión de su estructura, que ocasiona pérdida de la elasticidad de la pared vascular y una permeabilidad anormal de esta a las proteínas (disfunción endotelial), así como aumento de la génesis de especies reactivas del oxígeno. La unión de productos finales de la glucosilación avanzada a sus receptores de membrana favorece la producción citoquinas y factores de crecimiento por los macrófagos y células mesangiales. Todo lo anterior favorece al desarrollo de aterosclerosis. Los productos finales de la glucosilación avanzada desempeñan un importante papel en el desarrollo de las complicaciones microvasculares y macrovasculares en el diabético. El control metabólico estricto de la glucemia y, en la actualidad, la terapéutica farmacológica con agentes que inhiben la formación de productos finales de la glucosilación avanzada o tienen acción antioxidante, constituyen alternativas terapéuticas para la prevención y solución del problema de las complicaciones crónicas de la diabetes mellitus(AU)

Hyperglycemia is nowadays considered as a fundamental pathogenic factor for development of diabetic neurovascular complications and, specifically, plays a prevailing role in phenomenon of non-enzymatic glycosylation and the formation of end-products of advanced glycosylation. Objetives: to describe the mechanisms of end-products of advanced glycosylation and its relation to complications of diabetes mellitus. The above mentioned end-products are produced by the non-enzymatic reaction of glucose and other derivatives including glioxal, methylglioxal and 3-desoxiblucosone with amines groups of long-life proteins. The glycosylation changes the structure, the physical-chemical properties and the function of intracellular and extracellular proteins. In basal membrane of small vessels it is produced a thickening and a structure distortion provoking the elasticity of the vascular wall and its abnormal permeability to proteins (endothelial dysfunction), as well as an increase of genesis of oxygen-reactive species. The link of end-products of advanced glycosylation with its membrane receptors favor the production of cytokines and growth factors by macrophages and mesangial cells. All above mentioned favor the development of atherosclerosis. The end-products of advanced glycosylation play a significant role in the development of microvascular and macrovascular complications in the diabetic patient. The strict metabolic control of glycemia and at present time, the pharmacologic therapeutics including agents inhibiting the formation of end-products of the advanced glycosylation have antioxidant action or are therapeutical alternatives for prevention and solution of the problem related to chronic complications of diabetes mellitus(AU)

Influence of dihydromyricetin on oxidation and non-enzymatic glycosylation in impaired glucose tolerance rats / 吉林大学学报(医学版)

Objective To study the influence of dihydromyricetin on the oxidation and non-enzymatic glycosylation in impaired glucose tolerance rats.Methods Animal model of impaired glucose tolerance rat was built by intragastrical(i.g.) injection of D-galactose generally.After 8 weeks intragastrical(i.g.) injection of dihydromyricetin(experimental group) and metformin (positive control),the levels of fasting blood glucose and tow-hour postprandial blood glucose,the insulin level and its resistance index,the levels of glycosylated hemoglobin (GHb) and advanced glycation end-products(AGEs) were detected,and the activities of superoxide dismutase(SOD) and glutathione peroxidase (GSH-Px),the content of malondiadehyde(MDA) were determined respectively.Results Compared with model group,dihydromyricetin decreased the level of two-hour postprandial blood glucose (P0.05).Conclusion Dihydromyricetin can significantly improve the state of impaired glucose tolerance rats; the mechanism may be related to its effect of improving the antioxidant activity of GSH-Px,inhibiting non-enzymatic glycation,lowering body oxidative stress and insulin resistance and promoting the use of blood glucose in peripheral organizations.