Xiaoxing Yin

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.

HILIC‐MS for metabolomics: An attractive and complementary approach to RPLC‐MS

Hydrophilic interaction chromatography (HILIC) is an emerging separation mode of liquid chromatography (LC). Using highly hydrophilic stationary phases capable of retaining polar/ionic metabolites, and accompany with high organic content mobile phase that offer readily compatibility with mass spectrometry (MS) has made HILIC an attractive complementary tool to the widely used reverse-phase (RP) chromatographic separations in metabolomic studies. The combination of HILIC and RPLC coupled with an MS detector expands the number of detected analytes and provides more comprehensive metabolite coverage than use of only RP chromatography. This review describes the recent applications of HILIC-MS/MS in metabolomic studies, ranging from amino acids, lipids, nucleotides, organic acids, pharmaceuticals, and metabolites of specific nature. The biological systems investigated include microbials, cultured cell line, plants, herbal medicine, urine, and serum as well as tissues from animals and humans. Owing to its unique capability to measure more-polar biomolecules, the HILIC separation technique would no doubt enhance the comprehensiveness of metabolite detection, and add significant value for metabolomic investigations.

The Akt-FoxO3a-manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy.

•  What is the central question of this study? Oxidative stress is known to play an important role in the development and progression of diabetic nephropathy. However, the mechanism of overproduction of reactive oxygen species (ROS) in high‐glucose conditions is not completely clear. •  What is the main finding and its importance? We demonstrated that high‐glucose concentrations induced excessive production of ROS and stimulated the phosphoinositide 3‐kinase–Akt–FoxO3a signalling pathway via the upregulation of transforming growth factor‐β1, resulting in phosphorylation and inactivation of FoxO3a and a reduction in the expression of its target gene, FoxO3a‐dependent manganese superoxide dismutase, and then further excessive production of ROS.

Preventive effects of rutin on the development of experimental diabetic nephropathy in rats.

AIMS Diabetic nephropathy (DN) is an important microvascular complication and one of the main causes of end-stage renal disease. In this study, the preventive effect and mechanism of rutin on the development of DN in streptozotocin (STZ)-induced diabetic rats were investigated. MAIN METHODS After an early DN model was induced by STZ, rats were orally administered rutin at 3 doses for 10 weeks. Fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), urine protein, kidney index, antioxidase, advanced glycosylation end products (AGEs), extracellular matrix (ECM) including collagen IV and laminin, connective tissue growth factor (CTGF), phosphorylated Smad 2/3 (p-Smad 2/3) and Smad 7 (p-Smad 7), and transforming growth factor-β(1) (TGF-β(1)) were determined by different methods, respectively. The ultrastructural morphology was observed by a transmission electron microscope. KEY FINDINGS Compared with the DN group, rutin decreased the levels of fasting blood glucose, Cr, BUN, urine protein, the intensity of oxidative stress and p-Smad 7 significantly. The expression of AGEs, collagen IV and laminin, TGF-β(1), p-Smad 2/3 and CTGF was inhibited by rutin significantly. Moreover, rutin was observed to inhibit proliferation of mesangial cells and decrease thickness of glomerular basement membrane (GBM) by electron microscopy. SIGNIFICANCE The preventive effect of rutin on the development of DN is closely related to oxidative stress and the TGF-β(1)/Smad/ECM and TGF-β(1)/CTGF/ECM signaling pathways. Those results suggest that rutin can prevent the development of experimental DN in rats.

Protective effect of l-citrulline against ethanol-induced gastric ulcer in rats.

We examined the protective effect of l-citrulline on ethanol-induced gastric ulcer in rats. Administration of l-citrulline at doses of 300, 600 and 900mg/kg body weight prior to ethanol ingestion protected the stomach from ulceration. The gastric lesions were significantly attenuated by all doses of l-citrulline as compared to the ethanol group. Pre-treatment with l-citrulline prevented the oxidative damage and the decrease of nitric oxide content as well as the increase of the myeloperoxidase activity. Consequently, significant changes observed included the attenuation in the elevation in total nitric oxide synthase activity and inducible nitric oxide synthase activity as well as the decrease in constitutive nitric oxide synthase activity in the gastric mucosa induced by ethanol. Analysis of serum cytokines of ethanol-induced rats showed a moderate decrease in interleukin-10 with considerable increase of interleukin-6 while l-citrulline inhibited the acute alteration of cytokines. These results suggested the gastroprotective effect of l-citrulline.

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.

Antidepressant-like effects of tea polyphenols on mouse model of chronic unpredictable mild stress

Tea polyphenols (TPs), which are the natural compounds extracted from tea leaves, possess a number of beneficial properties, such as reducing the risks of cancer and heart diseases, alleviating cognitive impairments and showing antidepressant-like activity in the forced swim test (FST) and tail suspension test (TST). The present study was designed to investigate the protective effect of TPs on the chronic unpredictable mild stress (CUMS)-induced depression model in mice and to elucidate the related underlying mechanisms. With the daily exposure to stressor for 5 consecutive weeks, TPs were administered in mice at a daily dose of 25 mg/kg or 50 mg/kg by gavage for 3 consecutive weeks from the 3rd week. Our results showed that CUMS significantly decreased the levels of serum serotonin (5-HT) and norepinephrine (NE) in the hippocampus, the prefrontal cortex and serum, and the activities of superoxide dismutase (SOD) and catalase (CAT), with an increase in lipid peroxidation level as well as a reduction in glutathione (GSH) level and an elevation in the production of malondialdehyde (MDA) in the hippocampus and the prefrontal cortex. CUMS also reduced open-field activity, sucrose consumption, as well as increased immobility duration in FST and TST. TPs administration could effectively reverse the alterations in the concentrations of 5-HT and NE, elevate the activities of SOD and CAT as well as the level of GSH, reduce the MDA level and inhibit lipid peroxidation. Moreover, TPs could effectively reverse alterations in immobility duration, sucrose consumption and open-field activity. In conclusion, TPs administration has exhibited significant antidepressant-like effects in mice with CUMS-induced depression. The antidepressant activity of TPs might be related to the alteration of monoaminergic responses and antioxidant defenses.

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