Curcumin alleviates immune‐complex‐mediated glomerulonephritis in factor‐H‐deficient mice

Abstract

SummaryComplement factor H (Cfh) is a key regulator of the complement cascade and protects C57BL/6 mice from immune complex-mediated complement-dependent glomerulonephritis. In chronic serum sickness (CSS) there are increased deposits of immune complexes in the glomeruli with inflammation and a scarring phenotype. As cucurmin is an effective antiinflammatory agent and reduces complement activation, we hypothesized that it should alleviate renal disease in this setting. To determine the effectiveness of curcumin, an apoferritin-induced CSS model in Cfh-deficient (Cfh À/À ) mice was used. Curcumin treatment (30 mg/kg) given every day in parallel with apoferritin reduced glomerulonephritis and enhanced kidney function (blood urea nitrogen, 45Á4 AE 7Á5 versus 35Á6 AE 5Á1; albuminuria, 50Á1 AE 7Á1 versus 15Á7 AE 7Á1; glomerulonephritis, 2Á62 + 0Á25 versus 2 + 0Á3, P < 0Á05). In line with reduced IgG deposits in mice with CSS given curcumin, C9 deposits were reduced indicating reduced complement activation. Mice treated with curcumin had a significant reduction in the number of splenic CD19 + B cells and the ratio of CD19 : CD3 cells (P < 0Á05) with no change in the T-cell population. Myeloperoxidase assay showed reduced macrophages in the kidney. However, a significant reduction in the M2 subset of splenic macrophages by apoferritin was prevented by curcumin, suggesting a protective function. Curcumin treatment reduced mRNA expression of inflammatory proteins monocyte chemoattractant protein-1 and transforming growth factor-b and matrix proteins, fibronectin, laminin and collagen. Our results clearly illustrate that curcumin reduces glomerulosclerosis, improves kidney function and could serve as a therapeutic agent during serum sickness.

Curcumin protects against fructose-induced podocyte insulin signaling impairment through upregulation of miR-206

“…Curcumin is reported to reduce glomerulosclerosis, improve kidney function in factor‐H‐deficient mice , ameliorate macrophage infiltration in renal glomeruli of streptozotocin‐induced diabetic rats , and decrease proteinuria in New Zealand Black/White mice and glomerulonephritic animals . In our previous study, curcumin and pioglitazone inhibited PTP1B and increased p‐IR and p‐IRS‐1 to enhance Akt and ERK1/2 activation in the liver of fructose‐fed rats .…”

Renoprotective effect of the antioxidant curcumin: Recent findings

“…Curcumin significantly attenuated the reduction of serum GPx and the levels of urea, cystatin C, and MDA in serum and the increase of the MDA concentration, nitric oxide and protein carbonyl content in kidney of rats with I/R [15]. On the other hand, Jacob et al [41] observed, in mice with deficient immune response and glomerulonephritis injury, that curcumin administration reduces GS and improves renal function (evaluated by BUN and albuminuria), which was associated to a decrease in inflammatory markers (TGF-β and MCP-1) and matrix proteins (fibronectin, laminin and collagen).…”

Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lprmice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment

“…Our studies showing significantly increased oxidative damage in lupus patients [19][20][21] led us to investigate an antioxidant/anti-inflammatory agent known as curcumin, [22][23][24][25][26][27][28][29][30][31] obtained from the rhizome of Curcuma longa (turmeric). Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione), a naturally occurring 'nutraceutical', comprises 4-6% of turmeric.…”