Recent Advances of Curcumin in the Prevention and Treatment of Renal Fibrosis

Xuejiao Sun, Yi Liu, Cheng Li, Xiting Wang, Ruyuan Zhu, Chenyue Liu, Haixia Liu, Lili Wang, Rufeng Ma, Min Fu, Dongwei Zhang, Yu Li, Xuejiao Sun, Yi Liu, Cheng Li, Xiting Wang, Ruyuan Zhu, Chenyue Liu, Haixia Liu, Lili Wang, Rufeng Ma, Min Fu, Dongwei Zhang, Yu Li

Abstract

Curcumin, a polyphenol derived from the turmeric, has received attention as a potential treatment for renal fibrosis primarily because it is a relatively safe and inexpensive compound that contributes to kidney health. Here, we review the literatures on the applications of curcumin in resolving renal fibrosis in animal models and summarize the mechanisms of curcumin and its analogs (C66 and (1E,4E)-1,5-bis(2-bromophenyl) penta-1,4-dien-3-one(B06)) in preventing inflammatory molecules release and reducing the deposition of extracellular matrix at the priming and activation stage of renal fibrosis in animal models by consulting PubMed and Cnki databases over the past 15 years. Curcumin exerts antifibrotic effect through reducing inflammation related factors (MCP-1, NF-κB, TNF-α, IL-1β, COX-2, and cav-1) and inducing the expression of anti-inflammation factors (HO-1, M6PRBP1, and NEDD4) as well as targeting TGF-β/Smads, MAPK/ERK, and PPAR-γ pathways in animal models. As a food derived compound, curcumin is becoming a promising drug candidate for improving renal health.

Figures

Figure 1
Figure 1
The chemical structure of curcumin (a), C66 (b), and B06 (c).
Figure 2
Figure 2
Nrf2 signaling pathway. Nrf2, as a transcription factor, resides within cytoplasm binding to the actin-associated Keap1 protein and is normally degraded. Upon oxidation stress, the association will be disrupted, resulting in the translocation of Nrf2 to nuclei and then increased expression of cytoprotective enzymes (HO-1, SOD, etc.).
Figure 3
Figure 3
Curcumin plays a protective role at the priming and the activation stage of renal fibrosis. At the priming stage, curcumin reduces proinflammatory molecular activity and blocks inflammation associated signaling pathways. At the activation stage, curcumin inhibits the expression of renal fibrosis markers, rebuilds the redox balance, blocks MAPK/ERK pathway and TGF-β/Smads pathway, and increases PPAR-γ expression. NF-κB, nuclear factor-kappa B; MCP-1, monocyte chemotactic protein 1; ICAM-1, intercellular adhesion molecule 1; TNF-α, tumor necrosis factor α; IL-1β, interleukin-1β; Cav-1, Caveolin-1; MAPK, mitogen-activated protein kinase; cPLA2, cytosolic phospholipase A2; iPLA2, calcium-independent intracellular PLA2; COX, cyclooxygenase; HO-1, heme oxygenase-1; CCR7, chemokine receptor 7; CCL21, chemokine ligand 21; α-SMA, α smooth muscle actin; Fsp-1, fibroblast-specific protein 1; TGF, transforming growth factor; Sphk1, sphingosine kinase 1; S1P, sphingosine 1-phosphate; PPAR-γ, peroxisome proliferators-activated receptor-γ; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase; GSH, glutathione; MDA, malondialdehyde; iNOS, inducible nitric oxide synthase; NEDD4, neural precursor cell expressed, developmentally downregulated 4; M6PRBP1, mannose-6-phosphate receptor binding protein 1.

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