Purple corn anthocyanins inhibit diabetes-associated glomerular monocyte activation and macrophage infiltration.
Diabetic nephropathy (DN) is one of the major diabetic complications and the leading cause of end-stage renal disease. In early DN, renal injury and macrophage accumulation take place in the pathological environment of glomerular vessels adjacent to renal mesangial cells expressing proinflammatory mediators. Purple corn utilized as a daily food is rich in anthocyanins exerting disease-preventive activities as a functional food. This study elucidated whether anthocyanin-rich purple corn extract (PCA) could suppress monocyte activation and macrophage infiltration. In the in vitro study, human endothelial cells and THP-1 monocytes were cultured in conditioned media of human mesangial cells exposed to 33 mM glucose (HG-HRMC). PCA decreased the HG-HRMC-conditioned, media-induced expression of endothelial vascular cell adhesion molecule-1, E-selectin, and monocyte integrins-β1 and -β2 through blocking the mesangial Tyk2 pathway. In the in vivo animal study, db/db mice were treated with 10 mg/kg PCA daily for 8 wk. PCA attenuated CXCR2 induction and the activation of Tyk2 and STAT1/3 in db/db mice. Periodic acid-Schiff staining showed that PCA alleviated mesangial expansion-elicited renal injury in diabetic kidneys. In glomeruli, PCA attenuated the induction of intracellular cell adhesion molecule-1 and CD11b. PCA diminished monocyte chemoattractant protein-1 expression and macrophage inflammatory protein 2 transcription in the diabetic kidney, inhibiting the induction of the macrophage markers CD68 and F4/80. These results demonstrate that PCA antagonized the infiltration and accumulation of macrophages in diabetic kidneys through disturbing the mesangial IL-8-Tyk-STAT signaling pathway. Therefore, PCA may be a potential renoprotective agent treating diabetes-associated glomerulosclerosis.
Dept. of Food and Nutrition, Hallym Univ., Chuncheon, Republic of Korea.
Min-Kyung
MK
Kang
Jing
J
Li
Jung-Lye
JL
Kim
Ju-Hyun
JH
Gong
Su-Nam
SN
Kwak
Jung Han Yoon
JH
Park
Jae-Yong
JY
Lee
Soon Sung
SS
Lim
Young-Hee
YH
Kang
D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D019040:E-Selectin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D003313:Zea mays
D000872:Anthocyanins; D019040:E-Selectin; D016023:Integrins; D016209:Interleukin-8; D010936:Plant Extracts; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1