Epigallocatechin-3-gallate prevents inflammation and diabetes -Induced glucose tolerance through inhibition of NLRP3 inflammasome activation.

Epigallocatechin-3-gallate (EGCG), the primary polyphenol component of green tea, has been shown to inhibit both oxidation and inflammation. However, the exact mechanism through which EGCG exhibits anti-inflammatory effects remains unclear. In this study, we assessed the potential pathways by which EGCG regulates NLRP3 inflammasome activity in vitro. We found that EGCG inhibits caspase-1 activation and IL-1ß secretion by suppressing NLRP3 inflammasome activation in mouse bone marrow-derived macrophages (BMDMs). EGCG was also observed to block NLRP3-mediated ASC speckle formation and to alleviate pyroptosis in BMDMs. In addition, EGCG treatment could improve high-fat diet (HFD)-induced glucose tolerance and prevent NLRP3 inflammasome-dependent inflammation in a mouse model of HFD-induced type 2 diabetes (T2D). Taken together, our results show that EGCG is a general inhibitor of NLRP3 inflammasome activation and administration of EGCG in T2D mice could improve glucose tolerance in vivo.

Effect of Selenium-Enriched Garlic Oil against Cytotoxicity Induced by OX-LDL in Endothelial Cells.

Objective. To detect the effect of selenium-enriched garlic oil (Se-garlic oil) against cytotoxicity induced by ox-LDL in endothelial cells. Methods. Se-garlic oil was extracted by organic solvent extraction. High performance liquid chromatography (HPLC) was used to detect the content of allicin in the Se-garlic oil. Hydride generation atomic fluorescence spectrometry (HG-AFS) was used to detect the content of Se in the Se-garlic oil. ECV-304 cells were separated into five groups (blank, ox-LDL, and low-, medium-, and high-dose Se-garlic oil). Methyl thiazolyl tetrazolium (MTT) assay was used to detect the cytoactivity of each cell group after culturing for 24, 48, and 72 hours. Flow cytometry (FCM) stained with annexin V-FITC/PI was used to detect the apoptosis of the cells from the blank, Se-garlic oil, ox-LDL, and Se-garlic oil + ox-ldl groups after 48 hours of incubation. Results. The amount of allicin in Se-garlic oil was 142.66 mg/ml, while, in Se, it was 198 mg/kg. When ox-LDL was added to low-, medium-, and high-dose Se-garlic oil, the cell viability rates of ECV-304 cells treated in the three groups were all higher, while the apoptosis rates were significantly lower than those of the ox-LDL group (P < 0.05). However, there was no significant difference between the apoptosis rates of the blank, Se-garlic oil, and Se-garlic oil + ox-LDL groups (P > 0.05). Conclusion. Se-garlic oil could inhibit the cytotoxic effect induced by ox-LDL in endothelial cells.

Salt loading and potassium supplementation: effects on ambulatory arterial stiffness index and endothelin-1 levels in normotensive and mild hypertensive patients.

The authors investigated effects of excessive salt intake and potassium supplementation on ambulatory arterial stiffness index (AASI) and endothelin-1 (ET-1) in salt-sensitive and non-salt-sensitive individuals. AASI and symmetric AASI (s-AASI) were used as indicators of arterial stiffness. Plasma ET-1 levels were used as an index of endothelial function. Chronic salt-loading and potassium supplementation were studied in 155 normotensive to mild hypertensive patients from rural northern China. After 3 days of baseline investigation, participants were maintained sequentially for 7 days each on diets of low salt (51.3 mmol/d), high salt (307.7 mmol/d), and high salt+potassium (60 mmol/d). Ambulatory 24-hour blood pressure (BP) and plasma ET-1 were measured at baseline and on the last 2 days of each intervention. High-salt intervention significantly increased BP, AASI, s-AASI (all P<.001); potassium supplementation reversed increased plasma ET-1 levels. High-salt-induced changes in BP, s-AASI, and plasma ET-1 were greater in salt-sensitive individuals. Potassium supplementation decreased systolic BP and ET-1 to a significantly greater extent in salt-sensitive vs non-salt-sensitive individuals (P<.001). Significant correlations were identified between s-AASI and ET-1 change ratios in response to both high-salt intervention and potassium supplementation (P<.001). Reducing dietary salt and increasing daily potassium improves arterial compliance and ameliorates endothelial dysfunction.

Reversion of p-glycoprotein-mediated multidrug resistance in human leukemic cell line by diallyl trisulfide.

Multidrug resistance (MDR) is the major obstacle in chemotherapy, which involves multiple signaling pathways. Diallyl trisulfide (DATS) is the main sulfuric compound in garlic. In the present study, we aimed to explore whether DATS could overcome P-glycoprotein-(P-gp-)mediated MDR in K562/A02 cells, and to investigate whether NF-κB suppression is involved in DATS-induced reversal of MDR. MTT assay revealed that cotreatment with DATS increased the response of K562/A02 cells to adriamycin (the resistance reversal fold was 3.79) without toxic side effects. DATS could enhance the intracellular concentration of adriamycin by inhibiting the function and expression of P-gp, as shown by flow cytometry, RT-PCR, and western blot. In addition, DATS resulted in more K562/A02 cell apoptosis, accompanied by increased expression of caspase-3. The expression of NF-κB/p65 (downregulation) was significantly linked to the drug-resistance mechanism of DATS, whereas the expression of IκBα was not affected by DATS. Our findings demonstrated that DATS can serve as a novel, nontoxic modulator of MDR, and can reverse the MDR of K562/A02 cells in vitro by increasing intracellular adriamycin concentration and inducing apoptosis. More importantly, we proved for the first time that the suppression of NF-κB possibly involves the molecular mechanism in the course of reversion by DATS.