1.
Curcumin attenuates urinary excretion of albumin in type II diabetic patients with enhancing nuclear factor erythroid-derived 2-like 2 (Nrf2) system and repressing inflammatory signaling efficacies.
Yang, H, Xu, W, Zhou, Z, Liu, J, Li, X, Chen, L, Weng, J, Yu, Z
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2015;(6):360-7
Abstract
Curcumin has a therapeutic potential in treating diabetic kidney disease (DKD) while potential mechanisms underlining this beneficial effect remain to be elucidated. In the present study, curcumin intervention was performed in patients with Type II diabetes mellitus (T2DM) by oral intake of curcumin at the dose of 500 mg/day for a period of 15-30 days. Nephritic excretion of urinary micro-albumin (U-mAlb) and blood metabolic indexes were assessed before and after this intervention. In addition, the lipid oxidation index, malondialdehyde (MDA) in plasma and the status of anti-oxidative Nrf2 system in blood lymphocytes were measured. The effect of curcumin on inflammation was assessed by measuring plasma lipopolysaccharide (LPS) content and inflammatory signaling protein in blood lymphocytes. A self-comparison method was used for assessing statistical significances of these measurements. Here we show that curcumin intervention markedly attenuated U-mAlb excretion without affecting metabolic control of participated patients. In addition, curcumin reduced plasma MDA level with enhanced the Nrf2 system specifically regulated protein, NAD(P)H quinone oxidoreductase 1 (NQO-1) together with other anti-oxidative enzymes in patients' blood lymphocytes. Furthermore, we observed reduced plasma LPS content and increased IκB, an inhibitory protein on inflammatory signaling in patient's lymphocytes after curcumin administration. Finally, several gut bacterials important for maintaining gut barrier integrity and function were upregulated by curcumin.In conclusion, short-term curcumin intervention ablates DKD progress with activating Nrf2 anti-oxidative system and anti-inflammatory efficacies in patients with T2DM.
2.
The use of functional chemical-protein associations to identify multi-pathway renoprotectants.
Xu, J, Meng, K, Zhang, R, Yang, H, Liao, C, Zhu, W, Jiao, J
PloS one. 2014;(5):e97906
Abstract
Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p = 1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.