TianmaGouteng yin attenuates ischemic stroke-induced brain injury by inhibiting the AGE/RAGE pathway

Background:Ischemic stroke is characterized by permanent or transient obstruction of blood flow,leading to a growing risk factor and health burden.Tianmagouteng yin(TMG)is commonly used in Chinese medicine to treat cerebral ischemia.The aim of this study was to investigate the neuroprotective effects of TMG against ischemic stroke.Methods:Either permanent middle cerebral artery occlusion(pMCAO)or sham operation was performed on anesthetized Wistar male rats(n=36).Results:Results demonstrated that TMG administration reduced the infarction volume and mitigated the neurobehavioral deficits.Hematoxylin and eosin(HE)staining and Prussian blue staining revealed that TMG attenuated tissue disruption and microbleeds in hippocampus tissues.In addition,TMG down-regulated the receptor of advanced glycation end products(RAGE)and p-JAK2.It also inhibited the concentrations of advanced glycation end products(AGEs),ferritin,malondialdehyde(MDA),and reactive oxygen species(ROS).Conclusion:As repetitive clinical trials of neuroprotectants targeting stroke have failed previously,our results suggested that the natural product,TMG,can probably help in the vicious cycles of ischemic stroke pathology.

Aged Garlic Extract Reduces ROS Production and Cell Death Induced by 6-Hydroxydopamine through Activation of the Nrf2-ARE Pathway in SH-SY5Y Cells

Many degenerative or pathological processes, such as aging, cancer and coronary heart disease, are related to reactive oxygen species (ROS) and radical-mediated reactions. We examined the effectiveness of aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, for protection of cells from ROS produced by 6-hydroxy-dopamine (6-OHDA) using human neuroblastoma SH-SY5Y cells. Concomitant treatment of cells with AGE (2 and 4 mg/ml) showed the dose-dependent protective effect on the cell death induced by 6-OHDA. In addition, the AGE treatment significantly suppressed the increase of ROS generation by 6-OHDA. Furthermore, the protective effect of AGE was accompanied by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the increase of mRNAs of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. These two enzymes are important in the cellular antioxidant system. These results indicated that AGE protected cells from ROS damage by not only capturing ROS directly but also activating the cellular antioxidant system by stimulating antioxidant gene expression via the Nrf2-ARE pathway. The present study suggested that AGE may be useful for prevention and treatment of cell damage caused by ROS.

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway

The aim of this study was to investigate the effects of high-advanced glycation end products （AGEs） diet on diabetic vascular complications. The Streptozocin （STZ）-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators 3f renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic sharacteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein （CRP）, low density lipoprotein （LDL）, tumor necrosis factor-a （TNF-a）, and interleukin-6 （IL-6） in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial ceils, mesangial cells and podocytes in renal ：ortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species ＇,ROS） and low-levels of superoxide dismutase （SOD） in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

Anti-diabetic potential of apigenin,luteolin,and baicalein via partially activating PI3K/Akt/GLUT-4 signaling pathways in insulin-resistant HepG2 cells

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities.In this study,apigenin,luteolin,and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant(IR)HepG2 cells.All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4(GLUT4)and phosphor-glycogen synthase kinase(GSK-3β).These fl avonoids signifi cantly inhibited the production of reactive oxygen species(ROS)and advanced glycation end-products(AGEs),which were closely related to the suppression of the phosphorylation form of NF-κB and P65.The expression levels of insulin receptor substrate-1(IRS-1),insulin receptor substrate-2(IRS-2)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway in IR-HepG2 cells were all partially activated by the fl avonoids,with variable effects.Furthermore,the intracellular metabolic conditions of the fl avonoids were also evaluated.

西红花酸对晚期糖化终产物诱导内皮细胞晚期糖基化终产物受体表达的抑制作用(英文)

目的:研究西红花酸对晚期糖基化终产物(AGE)诱导牛内皮细胞(BEC)中晚期糖基化终产物受体(RAGE)mRNA表达的抑制作用,并探讨其可能机制。方法:不同浓度的西红花酸(1、0.1、0.01μmol/L)预孵BEC细胞12h后,用AGE(100mg/L)刺激细胞12h,RT-PCR法测定RAGEmRNA的表达水平;ELISA法测定细胞间黏附分子-1(ICAM-1)的表达;试剂盒分别检测胞外超氧阴离子和硫代巴比妥酸反应产物(TBARS)浓度;同时,还用2,7-二氯荧光素(DCFH)测定了胞内H2O2的浓度,并用罗丹明123(Rh123)荧光法及MTT法分别检测细胞线粒体膜电位(MMP)水平和其琥珀酸脱氢酶(MSDH)的活性。结果:与AGE模型组相比,西红花酸能显著抑制RAGE mRNA的表达(P<0.05),降低胞外超氧阴离子和TBARS(P<0.01或P<0.05)及胞内H2O2水平;结果还显示,西红花酸能提高细胞MMP水平和MSDH活性。对ICAM-1蛋白表达也有抑制作用,且呈时间和剂量依赖性。结论:西红花酸可能通过清除AGE与RAGE结合产生的活性氧(ROS)来抑制RAGE mRNA的高表达。提示西红花酸对糖尿病血管病变有潜在的治疗价值。