Jian-yun Wang

Ginsenoside Re attenuates diabetes-associated cognitive deficits in rats.

OBJECTIVE This study was designed to investigate the effect of ginsenoside Re (Re) on cognitive functions, oxidative stress and inflammation in streptozotocin-induced diabetic rats. RESEARCH DESIGN AND METHOD Diabetic rats were treated with Re (40mg/kg) for 8weeks, blood glucose and body weight were measured monthly and weekly, respectively. Cognitive performances were evaluated with Morris water maze. Brain was obtained for measurements of TNF-α and malondialdehyde (MDA) contents in both temporal cortex and hippocampus, blood was collected for assays of TNF-α, MDA and reduced glutathione (GSH) levels. RESULTS Learning and memory abilities were significantly (both P<0.01) impaired in diabetic rats, accompanied by the marked (all P<0.01) elevations of TNF-α and MDA levels in temporal cortex and hippocampus. Increment of MDA and decrement of GSH in serum also occurred with significant differences (both P<0.01). Chronic treatment with Re markedly (P<0.05) improved the cognition of diabetic rats, evidenced by the decreased escape latency and the increased percentage of time spent in the target quadrant. Furthermore, Re treatment remarkably (P<0.05) reduced the levels of TNF-α and MDA in both brain areas of diabetic rats. Decline of MDA level and elevation of GSH level in serum were also seen in Re-treated diabetic rats, coupled with decrease in serum glucose level, all with statistically significant differences. CONCLUSIONS Our findings firstly provide the first evidence that ginsenoside Re can remarkably attenuate diabetes-associated cognitive decline, secondly confirm the involvement of oxidative stress and inflammation in the development of cognitive impairment caused by diabetes, finally point toward the potential of ginsenoside Re as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as diabetes-associated cognitive decline.

Effects of Ginkgo biloba on prevention of development of experimental diabetic nephropathy in rats

AbstractAim:To observe the preventive and therapeutic effects of Ginkgo biloba extract (GbE) on early experimental diabetic nephropathy (DN) in rats.Methods:After an early DN model was induced by streptozotocin, rats were administered GbE at 3 doses for 12 weeks. Fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), urine protein, kidney index, anti-oxidase, advanced glycosylation end products (AGE), collagen IV and laminin, matrix metalloproteinases-2 (MMP-2) and the tissue inhibitor of metalloproteinase-2 (TIMP-2), connective tissue growth factor (CTGF), and transforming growth factor-β1 (TGF-β1) mRNA were measured by different methods. The ultrastructural morphology and the thickness of glomerular base membrane (GBM) were observed by a transmission electron microscope.Results:For the GbE-treated DN rats, when compared with the vehicle-treated DN rats, the fasting blood glucose level, Cr, BUN, urine protein level, and the intensity of oxidative stress were significantly decreased. The expression of MMP-2 greatly increased, and TIMP-2 decreased. Also, AGE, either in serum or in renal, the collagen IV, laminin, CTGF levels, and TGF-β1 mRNA were reduced. Furthermore, both relative grades of mesangium hyperplasia by microscopical observation and the thickness of GBM by electron microscope measurement decreased significantly.Conclusion:GbE has protective effects on several pharmacological targets in the progress of DN and is a potential drug for the prevention of early DN.

Total saponins from Rhizoma Anemarrhenae ameliorate diabetes-associated cognitive decline in rats: Involvement of amyloid-beta decrease in brain

ETHNOPHARMACOLOGICAL RELEVANCE As a well-known Chinese Materia Medica Rhizoma Anemarrhenae has multiple pharmacological activities including antipyretic, anti-inflammatory, anti-diabetic actions, etc. This study was designed to investigate effects of total saponins from Rhizoma Anemarrhenae (TS) on diabetes-associated cognitive decline in rats and influence on amyloid-beta (Aβ) levels in brain and inflammation. MATERIALS AND METHODS Diabetic rats induced by intraperitoneal administration of streptozotocin, were randomized into two groups: diabetes and TS-treated diabetes. Blood glucose and body weight were measured monthly and weekly, respectively. After seven weeks, cognitive performances were evaluated with Morris water maze. Then, brain was obtained for assay of Aβ and TNF-α levels, and blood was collected for TNF-α assay. RESULTS Aβ(1-40), Aβ(1-42) and TNF-α levels were dramatically (all P<0.01) increased both in temporal cortex and hippocampus of diabetic rats, coupled with impairment of cognition, compared with those of the control. Chronic TS (200mg/kg) treatment markedly (P<0.05) improved the learning ability of diabetic rats, and significantly (all P<0.05) reduced Aβ(1-40), Aβ(1-42) and TNF-α levels in cortex as well as Aβ(1-40) level in hippocampus, whereas showed a decreased tendency for Aβ(1-42) and TNF-α levels in hippocampus. Moreover, eight-week treatment with TS remarkably (P<0.05) inhibited the elevation of TNF-α level in serum of diabetic rats, and significantly (both P<0.01) decrease the fasting blood glucose level and increase the body weight of diabectic rats. CONCLUSION Our findings demonstrate that diabetes-associated cognitive decline is, at least in part, due to brain Aβ accumulation in diabetic condition, and efficacy of TS to diabetes-associated cognitive decline in rats is a sum of reduction of Aβ accumulation and inflammation in brain as well as attenuation of major symptoms of diabetes.

Up-regulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats.

Advanced glycation endproducts (AGEs) and its precursor methylglyoxal are associated with diabetic nephropathy (DN). Mangiferin has many beneficial biological activities, including anti-inflammatory, anti-oxidative and anti-diabetic effects. We investigated the effect of mangiferin on DN and its potential mechanism associated with glyoxalase 1 (Glo-1), a detoxifying enzyme of methylglyoxal, in streptozotocin-induced rat model of DN. Diabetic rats were treated orally with mangiferin (15, 30, and 60 mg/kg) or distilled water for 9 weeks. Kidney tissues were collected for morphologic observation and the determination of associated biochemical parameters. The cultured mesangial cells were used to measure the activity of Glo-1 in vitro. Chronic treatment with mangiferin significantly ameliorated renal dysfunction in diabetic rats, as evidenced by decreases in albuminuria, blood urea nitrogen, kidney weight index, periodic acid-schiff stain positive mesangial matrix area, glomerular extracellular matrix expansion and accumulation, and glomerular basement membrane thickness. Meanwhile, mangiferin treatment caused substantial increases in the enzymatic activity of Glo-1 in vivo and in vitro, and protein and mRNA expression of Glo-1, reduced levels of AGEs and the protein and mRNA expression of their receptor (RAGE) in the renal cortex of diabetic rats. Moreover, mangiferin significantly attenuated oxidative stress damage as reflected by the lowered malondialdehyde and the increased glutathione levels in the kidney of diabetic rats. However, mangiferin did not affect the blood glucose and body weight of diabetic rats. Therefore, mangiferin can remarkably ameliorate DN in rats through inhibiting the AGEs/RAGE aix and oxidative stress damage, and Glo-1 may be a target for mangiferin action.

Ginkgo biloba extract prevents glucose‐induced accumulation of ECM in rat mesangial cells

Pathological remodeling characterized by extracellular matrix (ECM) accumulation contributes to diabetic nephropathy (DN). This study evaluated the effects of Ginkgo biloba extract (GbE) on the metabolism of the ECM in rat mesangial cells cultured in hyperglycemic conditions. The cultured mesangial cells in high glucose conditions were allotted into six groups: normal control group, high glucose group, low concentration of GbE group, moderate concentration of GbE group, high concentration of GbE group, and captopril group. In the presence of high glucose, the levels of matrix metalloproteinase‐2 (MMP‐2), matrix metalloproteinase‐9 (MMP‐9) and extracellular matrix metalloproteinase inducer (EMMPRIN) were decreased significantly, and the levels of tissue inhibitor of metalloproteinase‐2 (TIMP‐2), tissue inhibitor of metalloproteinase‐1 (TIMP‐1) and plasminogen activator inhibitor‐1 (PAI‐1) were increased significantly. These changes were reversed by GbE. GbE lowered the levels of transforming growth factor‐β1 (TGF‐β1), insulin‐like growth factor‐1 (IGF‐1) and connective tissue growth factor (CTGF) of the high glucose group. Furthermore, GbE also decreased the expressions of collagen IV and laminin of the high glucose group. In summary, the results suggest that GbE postpones the extracellular matrix accumulation by inhibiting the synthesis of ECM and promoting the degradation of ECM, and therefore, is a potential drug for the prevention and treatment of DN. Copyright

Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells

AbstractAim:To investigate the protective effects of Ginkgo biloba extract (GBE) on high glucose-induced apoptosis of human lens epithelial cells (HLEC) and the possible molecular mechanisms.Methods:The cultured HLEC were allotted into 6 groups: normal group, high glucose group, low-, moderate-, and highdose GBE group, and the bendazac lysine group. Cell viability, cell apoptosis, the activities of cell antioxidases, aldose reductase, caspase-3, the levels of cell antioxidants, and the expressions of Bcl-2 and Bax were assessed by different methods.Results:After being incubated with high glucose for 24 h, HLEC underwent apoptosis and exhibited significant oxidative stress. In the presence of GBE at different doses, the rate of HLEC apoptosis was lower and the oxidative stress state was significantly ameliorated. The increased ratio of Bax to Bcl-2 was significantly reduced and the activation of caspase-3 was suppressed by GBE in a dose-dependent manner.Conclusion:GBE prevents HLEC from high glucose-induced apoptosis through inhibiting oxidative stress, reducing the ratio of Bax to Bcl-2, and decreasing the activity of caspase-3. Therefore, GBE has a potential protective effect against diabetic cataract formation.

In vitro suppression of quercetin on hypertrophy and extracellular matrix accumulation in rat glomerular mesangial cells cultured by high glucose

Quercetins protective effects on the glomerulosclerosis of diabetic nephropathy (DN) in rat mesangial cells were investigated. The cell cycles, type IV collagen and laminin, TGF-β(1) mRNA, Smad 2/3 and Smad 7, and activities of cell antioxidases were measured. Compared with the high glucose group, quercetin may decrease the cell percentages of G(0)/G(1) phase, Smad 2/3 expression, laminin and type IV collagen, and TGF-β(1) mRNA level significantly. The antioxidant capacity, the cell percentages of S phase and Smad 7 expression was significantly increased by quercetin. These results suggest that quercetin is a protective agent against glomerulosclerosis in DN.

Tetrahydrobiopterin contributes to the proliferation of mesangial cells and accumulation of extracellular matrix in early-stage diabetic nephropathy

Nitric oxide (NO) plays an important role in the progression of early‐stage diabetic nephropathy (DN), which is found to contribute to extracellular matrix (ECM) accumulation in mesangial cells (MCs). As a cofactor for NO production, tetrahydrobiopterin (BH4), a folacin analogue, may be responsible for the ECM accumulation and proliferation of MCs. This study was to investigate the effects of BH4 on glomerulosclerosis in early‐stage DN.

Jak2/Stat1 pathway mediated tetrahydrobiopterin up-regulation contributes to nitric oxide overproduction in high-glucose cultured rat mesangial cells.

Nitric oxide (NO) is crucial for the progression of early diabetic nephropathy (DN). It is important to clarify the mechanism for the production of NO in mesangial cells (MCs). In this study, the amounts/activities of related factors such as reactive oxygen species (ROS), NO, 3 isoforms of nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), GTP cyclohydrolase I (GTPCH I), Jak2, and Stat1 were determined using high-glucose cultured rat MCs. The results showed that the production of BH4 under oxidative stress was strongly stimulated by its rate-limiting enzyme GTP cyclohydrolase, which increased the expression and activity of inducible NOS to facilitate NO synthesis. Furthermore, the relative quantities of activated-Jak2 and activated-Stat1 were increased. Therefore, Jak2/Stat1 pathway mediated BH4 up-regulation can contribute to excessive NO in high-glucose cultured MCs. Our results will be helpful for screening new targets to improve the therapy for early DN.