Neuroprotection of quercetin on central neurons against chronic high glucose through enhancement of Nrf2/ARE/glyoxalase-1 pathway mediated by phosphorylation regulation.

Although dietary flavonoid quercetin alleviates diabetes-associated cognitive decline in rodents, the mechanisms are not clearly clarified. This study was designed to investigate whether quercetin showed neuroprotection on central neurons against chronic high glucose through the enhancement of Nrf2/ARE/glyoxalase 1 (Glo-1) pathway. SH-SY5Y cells were divided into 8 groups: normal glucose, high glucose (HG), osmotic pressure control, solvent control, HG plus low, middle, high concentrations of quercetin, or Nrf2 activator (sulforaphane). After treatment for 72 h, the associated parameters were measured. We found quercetin and sulforaphane increased cell viability, and enhanced Glo-1 functions (Glo-1 activity, the reduced glutathione and advanced glycation end-products levels) as well as Glo-1 protein and mRNA levels in SH-SY5Y cells cultured with HG. Meanwhile, quercetin and sulforaphane activated Nrf2/ARE pathway, reflected by the raised Nrf2 and p-Nrf2 levels, and the elevated protein and mRNA levels of γ-glutamycysteine synthase (γ-GCS), a known target gene of Nrf2/ARE signaling. Moreover, Nrf2/ARE pathway was activated after pretreatment with a PKC activator, p38 MAPK inhibitor, or GSK-3ß inhibitor under the condition of HG, and quercetin addition further strengthened this pathway; however, PKC inhibition or GSK-3ß activation pretreatment reversed the effects of quercetin on the protein expression of γ-GCS in the HG condition. In summary, quercetin exerts the neuroprotection by enhancing Glo-1 functions in central neurons under chronic HG condition, which may be mediated by activation of Nrf2/ARE pathway; furthermore, the increased Nrf2 phosphorylation mediated by PKC activation and/or GSK-3ß inhibition may involve in the activation of Nrf2/ARE pathway.

Protective effects of sarsasapogenin against early stage of diabetic nephropathy in rats.

Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal saponins from AA show good antidiabetes effects and ameliorate diabetic complications. This study was designed to investigate the effects of sarsasapogenin (Sar), a major sapogenin from AA, on diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in albuminuria, kidney weight index, serum uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (fibronectin and collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in interleukin-18, NLRP3, and activated caspase 1 levels as well as advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate diabetic nephropathy in rats via inhibition of NLRP3 inflammasome activation and AGEs-RAGE interaction.

Mangiferin Upregulates Glyoxalase 1 Through Activation of Nrf2/ARE Signaling in Central Neurons Cultured with High Glucose.

Mangiferin, a natural C-glucoside xanthone, has anti-inflammatory, anti-oxidative, neuroprotective actions. Our previous study showed that mangiferin could attenuate diabetes-associated cognitive impairment of rats by enhancing the function of glyoxalase 1 (Glo-1) in brain. The aim of this study was to investigate whether Glo-1 upregulation by mangiferin in central neurons exposed to chronic high glucose may be related to activation of Nrf2/ARE pathway. Compared with normal glucose (25 mmol/L) culture, Glo-1 protein, mRNA, and activity levels were markedly decreased in primary hippocampal and cerebral cortical neurons cultured with high glucose (50 mmol/L) for 72 h, accompanied by the declined Nrf2 nuclear translocation and protein expression of Nrf2 in cell nucleus, as well as protein expression and mRNA level of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase activity, target genes of Nrf2/ARE signaling. Nonetheless, high glucose cotreating with mangiferin or sulforaphane, a typical inducer of Nrf2 activation, attenuated the above changes in both central neurons. In addition, mangiferin and sulforaphane significantly prevented the formation of advanced glycation end-products (AGEs) reflecting Glo-1 activity, while elevated the level of glutathione, a cofactor of Glo-1 activity and production of γ-GCS, in high glucose cultured central neurons. These findings demonstrated that Glo-1 was greatly downregulated in central neurons exposed to chronic high glucose, which is expected to lead the formation of AGEs and oxidative stress damages. We also proved that mangiferin enhanced the function of Glo-1 under high glucose condition by inducing activation of Nrf2/ARE signaling pathway.

Tracking historical lead pollution in the coastal area adjacent to the Yangtze River Estuary using lead isotopic compositions.

The rapid economic development in the Yangtze River Delta (YRD), China in the last three decades has had a significant impact on the environment of the East China Sea (ECS). Lead isotopic compositions of a (210)Pb dated sediment core collected from the coastal ECS adjacent to the Yangtze River Estuary were analyzed to track the Pb pollution in the region. The baseline Pb concentration in the coastal ECS sediments before the industrialization in China was 32 microg g(-1), and the corresponding 206Pb/207Pb ratio was 1.195. The high-resolution profiles of Pb flux and 206Pb/207Pb ratios had close relationships with the economic development and the history of the use of leaded gasoline in China, and they were clearly different from those of most European countries and United States.

The sedimentary fluxes of polycyclic aromatic hydrocarbons in the Yangtze River Estuary coastal sea for the past century.

Polycyclic aromatic hydrocarbons (PAHs) in two (210)Pb dated sediment cores from the coastal East China Sea, strongly influenced by the discharge from the Yangtze River, were determined to help to reconstruct the economic development over the past century in East China. The variations in PAH concentrations and fluxes in the sediment cores were primarily due to energy structure change, severe floods and dam construction activities. The impact on PAHs by the river discharge overwhelmed the atmospheric depositions. The profiles of PAH fluxes and concentrations as well as compositions in the cores revealed the transformation from an agricultural economy to an industrial one especially after the 1990s' in the region. PAHs in the study area were dominated by pyrolytic sources.