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Published in: Inflammation 4/2017

01-08-2017 | ORIGINAL ARTICLE

Brazilin Ameliorates Diabetic Nephropathy and Inflammation in db/db Mice

Authors: Zhan-yuan Li, Yu Zheng, Yan Chen, Min Pan, Shu-bei Zheng, Wen Huang, Zhi-hong Zhou, Han-yang Ye

Published in: Inflammation | Issue 4/2017

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Abstract

Hyperglycemia and inflammation play important roles in the pathogenesis of diabetic nephropathy (DN). Brazilin might be an effective pharmacological agent against hyperglycemia and inflammation. In our present study, we explored whether brazilin mitigated pathological progression, inflammation, and extracellular matrix (ECM) accumulation in a mouse model of diabetic nephropathy. Brazilin reduced aggravated biochemical indices of DN (proteinuria and the serum glucose level) and renal hypertrophy. Brazilin also improved renal morphology and inhibited macrophage infiltration, as manifested by different pathological staining methods. Brazilin reduced the levels of pro-inflammatory cytokines and CD68, a macrophage marker, in the kidney cortex, as revealed by both RT-PCR and western blotting experiments. Furthermore, brazilin significantly downregulated the serum levels of pro-inflammatory cytokines and chemokines. Interestingly, brazilin significantly upregulated the levels of the anti-inflammatory factor IL-10, and prevented ECM accumulation. Brazilin reduced nuclear translocation of the NF-κB p65 subunit both in vitro and in vivo. Thus, brazilin might be a useful treatment for DN, through mitigating hypoglycemia, inflammation, and ECM accumulation.
Literature
1.
go back to reference Cobitz, A.R., and P. Ambery. 2009. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Response to Nathan et al. Diabetes Care 32 (5): e58; author rely e59. doi:10.2337/dc09-0125.CrossRefPubMed Cobitz, A.R., and P. Ambery. 2009. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Response to Nathan et al. Diabetes Care 32 (5): e58; author rely e59. doi:10.​2337/​dc09-0125.CrossRefPubMed
3.
go back to reference Navarro-Gonzalez, J.F., C. Mora-Fernandez, M. Muros de Fuentes, and J. Garcia-Perez. 2011. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nature Reviews. Nephrology 7 (6): 327–340. doi:10.1038/nrneph.2011.51.CrossRefPubMed Navarro-Gonzalez, J.F., C. Mora-Fernandez, M. Muros de Fuentes, and J. Garcia-Perez. 2011. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nature Reviews. Nephrology 7 (6): 327–340. doi:10.​1038/​nrneph.​2011.​51.CrossRefPubMed
4.
go back to reference Pichler, R., M. Afkarian, B.P. Dieter, and K.R. Tuttle. 2016. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Renal Physiol:ajprenal 00314: 02016. doi:10.1152/ajprenal.00314.2016. Pichler, R., M. Afkarian, B.P. Dieter, and K.R. Tuttle. 2016. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Renal Physiol:ajprenal 00314: 02016. doi:10.​1152/​ajprenal.​00314.​2016.
5.
go back to reference Bohle, A., M. Wehrmann, O. Bogenschutz, C. Batz, C.A. Muller, and G.A. Muller. 1991. The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. Pathology, Research and Practice 187 (2–3): 251–259.CrossRefPubMed Bohle, A., M. Wehrmann, O. Bogenschutz, C. Batz, C.A. Muller, and G.A. Muller. 1991. The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. Pathology, Research and Practice 187 (2–3): 251–259.CrossRefPubMed
8.
go back to reference Klessens, C.Q., M. Zandbergen, R. Wolterbeek, J.A. Bruijn, T.J. Rabelink, I.M. Bajema, and I. Jpelaar DH. 2016. Macrophages in diabetic nephropathy in patients with type 2 diabetes. Nephrology, Dialysis, Transplantation. doi:10.1093/ndt/gfw260.PubMed Klessens, C.Q., M. Zandbergen, R. Wolterbeek, J.A. Bruijn, T.J. Rabelink, I.M. Bajema, and I. Jpelaar DH. 2016. Macrophages in diabetic nephropathy in patients with type 2 diabetes. Nephrology, Dialysis, Transplantation. doi:10.​1093/​ndt/​gfw260.PubMed
10.
go back to reference Sullivan, T., Z. Miao, D.J. Dairaghi, A. Krasinski, Y. Wang, B.N. Zhao, T. Baumgart, et al. 2013. CCR2 antagonist CCX140-B provides renal and glycemic benefits in diabetic transgenic human CCR2 knockin mice. American Journal of Physiology. Renal Physiology 305 (9): F1288–F1297. doi:10.1152/ajprenal.00316.2013.CrossRefPubMedPubMedCentral Sullivan, T., Z. Miao, D.J. Dairaghi, A. Krasinski, Y. Wang, B.N. Zhao, T. Baumgart, et al. 2013. CCR2 antagonist CCX140-B provides renal and glycemic benefits in diabetic transgenic human CCR2 knockin mice. American Journal of Physiology. Renal Physiology 305 (9): F1288–F1297. doi:10.​1152/​ajprenal.​00316.​2013.CrossRefPubMedPubMedCentral
11.
go back to reference Gembardt, F., C. Bartaun, N. Jarzebska, E. Mayoux, V.T. Todorov, B. Hohenstein, and C. Hugo. 2014. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. American Journal of Physiology. Renal Physiology 307 (3): F317–F325. doi:10.1152/ajprenal.00145.2014.CrossRefPubMed Gembardt, F., C. Bartaun, N. Jarzebska, E. Mayoux, V.T. Todorov, B. Hohenstein, and C. Hugo. 2014. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. American Journal of Physiology. Renal Physiology 307 (3): F317–F325. doi:10.​1152/​ajprenal.​00145.​2014.CrossRefPubMed
12.
go back to reference Nirmal, N.P., and P. Panichayupakaranant. 2014. Anti-Propionibacterium acnes assay-guided purification of brazilin and preparation of brazilin rich extract from Caesalpinia sappan heartwood. Pharmaceutical Biology 52 (9): 1204–1207. doi:10.3109/13880209.2014.884607.CrossRefPubMed Nirmal, N.P., and P. Panichayupakaranant. 2014. Anti-Propionibacterium acnes assay-guided purification of brazilin and preparation of brazilin rich extract from Caesalpinia sappan heartwood. Pharmaceutical Biology 52 (9): 1204–1207. doi:10.​3109/​13880209.​2014.​884607.CrossRefPubMed
13.
14.
go back to reference Junior, W.S., A.H. Ladio, and U.P. Albuquerque. 2011. Resilience and adaptation in the use of medicinal plants with suspected anti-inflammatory activity in the Brazilian northeast. Journal of Ethnopharmacology 138 (1): 238–252. doi:10.1016/j.jep.2011.09.018.CrossRefPubMed Junior, W.S., A.H. Ladio, and U.P. Albuquerque. 2011. Resilience and adaptation in the use of medicinal plants with suspected anti-inflammatory activity in the Brazilian northeast. Journal of Ethnopharmacology 138 (1): 238–252. doi:10.​1016/​j.​jep.​2011.​09.​018.CrossRefPubMed
16.
go back to reference Won, H.S., J. Lee, L.Y. Khil, S.H. Chae, M.Y. Ahn, B.H. Lee, J.H. Chung, Y.C. Kim, and C.K. Moon. 2004. Mechanism of action of brazilin on gluconeogenesis in isolated rat hepatocytes. Planta Medica 70 (8): 740–744. doi:10.1055/s-2004-827205.CrossRefPubMed Won, H.S., J. Lee, L.Y. Khil, S.H. Chae, M.Y. Ahn, B.H. Lee, J.H. Chung, Y.C. Kim, and C.K. Moon. 2004. Mechanism of action of brazilin on gluconeogenesis in isolated rat hepatocytes. Planta Medica 70 (8): 740–744. doi:10.​1055/​s-2004-827205.CrossRefPubMed
17.
go back to reference Moon, C.K., S.H. Lee, M.O. Lee, and S.G. Kim. 1993. Effects of brazilin on glucose oxidation, lipogenesis and therein involved enzymes in adipose tissues from diabetic KK-mice. Life Sciences 53 (16): 1291–1297.CrossRefPubMed Moon, C.K., S.H. Lee, M.O. Lee, and S.G. Kim. 1993. Effects of brazilin on glucose oxidation, lipogenesis and therein involved enzymes in adipose tissues from diabetic KK-mice. Life Sciences 53 (16): 1291–1297.CrossRefPubMed
18.
go back to reference Gao, X.J., T.C. Wang, Z.C. Zhang, Y.G. Cao, N.S. Zhang, and M.Y. Guo. 2015. Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice. International Immunopharmacology 27 (1): 130–137. doi:10.1016/j.intimp.2015.04.043.CrossRefPubMed Gao, X.J., T.C. Wang, Z.C. Zhang, Y.G. Cao, N.S. Zhang, and M.Y. Guo. 2015. Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice. International Immunopharmacology 27 (1): 130–137. doi:10.​1016/​j.​intimp.​2015.​04.​043.CrossRefPubMed
19.
go back to reference Jia, Y., J. Zhao, M. Liu, B. Li, Y. Song, Y. Li, A. Wen, and L. Shi. 2016. Brazilin exerts protective effects against renal ischemia-reperfusion injury by inhibiting the NF-kappaB signaling pathway. International Journal of Molecular Medicine 38 (1): 210–216. doi:10.3892/ijmm.2016.2616.PubMedPubMedCentral Jia, Y., J. Zhao, M. Liu, B. Li, Y. Song, Y. Li, A. Wen, and L. Shi. 2016. Brazilin exerts protective effects against renal ischemia-reperfusion injury by inhibiting the NF-kappaB signaling pathway. International Journal of Molecular Medicine 38 (1): 210–216. doi:10.​3892/​ijmm.​2016.​2616.PubMedPubMedCentral
21.
go back to reference Kolati, S.R., E.R. Kasala, L.N. Bodduluru, J.R. Mahareddy, S.K. Uppulapu, R. Gogoi, C.C. Barua, and M. Lahkar. 2015. BAY 11-7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-kappaB pathway. Environmental Toxicology and Pharmacology 39 (2): 690–699. doi:10.1016/j.etap.2015.01.019.CrossRefPubMed Kolati, S.R., E.R. Kasala, L.N. Bodduluru, J.R. Mahareddy, S.K. Uppulapu, R. Gogoi, C.C. Barua, and M. Lahkar. 2015. BAY 11-7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-kappaB pathway. Environmental Toxicology and Pharmacology 39 (2): 690–699. doi:10.​1016/​j.​etap.​2015.​01.​019.CrossRefPubMed
22.
go back to reference Tucker, P.S., A.T. Scanlan, and V.J. Dalbo. 2015. Chronic kidney disease influences multiple systems: describing the relationship between oxidative stress, inflammation, kidney damage, and concomitant disease. Oxidative Medicine and Cellular Longevity 2015: 806358. doi:10.1155/2015/806358.CrossRefPubMedPubMedCentral Tucker, P.S., A.T. Scanlan, and V.J. Dalbo. 2015. Chronic kidney disease influences multiple systems: describing the relationship between oxidative stress, inflammation, kidney damage, and concomitant disease. Oxidative Medicine and Cellular Longevity 2015: 806358. doi:10.​1155/​2015/​806358.CrossRefPubMedPubMedCentral
23.
24.
go back to reference Lee, F.T., Z. Cao, D.M. Long, S. Panagiotopoulos, G. Jerums, M.E. Cooper, and J.M. Forbes. 2004. Interactions between angiotensin II and NF-kappaB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. Journal of the American Society of Nephrology 15 (8): 2139–2151. doi:10.1097/01.asn.0000135055.61833.a8.CrossRefPubMed Lee, F.T., Z. Cao, D.M. Long, S. Panagiotopoulos, G. Jerums, M.E. Cooper, and J.M. Forbes. 2004. Interactions between angiotensin II and NF-kappaB-dependent pathways in modulating macrophage infiltration in experimental diabetic nephropathy. Journal of the American Society of Nephrology 15 (8): 2139–2151. doi:10.​1097/​01.​asn.​0000135055.​61833.​a8.CrossRefPubMed
25.
go back to reference Navarro-Gonzalez, J.F., C. Mora-Fernandez, M. Muros de Fuentes, J. Chahin, M.L. Mendez, E. Gallego, M. Macia, et al. 2015. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. Journal of the American Society of Nephrology 26 (1): 220–229. doi:10.1681/ASN.2014010012.CrossRefPubMed Navarro-Gonzalez, J.F., C. Mora-Fernandez, M. Muros de Fuentes, J. Chahin, M.L. Mendez, E. Gallego, M. Macia, et al. 2015. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. Journal of the American Society of Nephrology 26 (1): 220–229. doi:10.​1681/​ASN.​2014010012.CrossRefPubMed
26.
go back to reference Khil, L.Y., A.J. Cheon, T.S. Chang, and C.K. Moon. 1997. Effects of calcium on brazilin-induced glucose transport in isolated rat epididymal adipocytes. Biochemical Pharmacology 54 (1): 97–101.CrossRefPubMed Khil, L.Y., A.J. Cheon, T.S. Chang, and C.K. Moon. 1997. Effects of calcium on brazilin-induced glucose transport in isolated rat epididymal adipocytes. Biochemical Pharmacology 54 (1): 97–101.CrossRefPubMed
27.
go back to reference Khil, L.Y., S.S. Han, S.G. Kim, T.S. Chang, S.D. Jeon, D.S. So, and C.K. Moon. 1999. Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes. Biochemical Pharmacology 58 (11): 1705–1712.CrossRefPubMed Khil, L.Y., S.S. Han, S.G. Kim, T.S. Chang, S.D. Jeon, D.S. So, and C.K. Moon. 1999. Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes. Biochemical Pharmacology 58 (11): 1705–1712.CrossRefPubMed
30.
go back to reference Giunti, S., G.H. Tesch, S. Pinach, D.J. Burt, M.E. Cooper, P. Cavallo-Perin, G. Camussi, and G. Gruden. 2008. Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells. Diabetologia 51 (1): 198–207. doi:10.1007/s00125-007-0837-3.CrossRefPubMed Giunti, S., G.H. Tesch, S. Pinach, D.J. Burt, M.E. Cooper, P. Cavallo-Perin, G. Camussi, and G. Gruden. 2008. Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells. Diabetologia 51 (1): 198–207. doi:10.​1007/​s00125-007-0837-3.CrossRefPubMed
31.
go back to reference Tewtrakul, S., P. Tungcharoen, T. Sudsai, C. Karalai, C. Ponglimanont, and O. Yodsaoue. 2015. Antiinflammatory and wound healing effects of Caesalpinia sappan L. Phytotherapy Research 29 (6): 850–856. doi:10.1002/ptr.5321.CrossRefPubMed Tewtrakul, S., P. Tungcharoen, T. Sudsai, C. Karalai, C. Ponglimanont, and O. Yodsaoue. 2015. Antiinflammatory and wound healing effects of Caesalpinia sappan L. Phytotherapy Research 29 (6): 850–856. doi:10.​1002/​ptr.​5321.CrossRefPubMed
32.
go back to reference Huang, X.R., A.R. Kitching, P.G. Tipping, and S.R. Holdsworth. 2000. Interleukin-10 inhibits macrophage-induced glomerular injury. Journal of the American Society of Nephrology 11 (2): 262–269.PubMed Huang, X.R., A.R. Kitching, P.G. Tipping, and S.R. Holdsworth. 2000. Interleukin-10 inhibits macrophage-induced glomerular injury. Journal of the American Society of Nephrology 11 (2): 262–269.PubMed
33.
go back to reference Li, C., H. Zhang, D. Gao, Q. Ma, Z. Li, J. Dai, M. Zhang, and C. Si. 2015. Aqueous extract of Caesalpinia sappan decelerates allograft rejection by inducing imbalance between CD4(+) CD25(+) T cells and Th17 cells. International Journal of Clinical and Experimental Medicine 8 (5): 7107–7115.PubMedPubMedCentral Li, C., H. Zhang, D. Gao, Q. Ma, Z. Li, J. Dai, M. Zhang, and C. Si. 2015. Aqueous extract of Caesalpinia sappan decelerates allograft rejection by inducing imbalance between CD4(+) CD25(+) T cells and Th17 cells. International Journal of Clinical and Experimental Medicine 8 (5): 7107–7115.PubMedPubMedCentral
34.
go back to reference Mueller, M., D. Weinmann, S. Toegel, W. Holzer, F.M. Unger, and H. Viernstein. 2016. Compounds from Caesalpinia sappan with anti-inflammatory properties in macrophages and chondrocytes. Food & Function 7 (3): 1671–1679. doi:10.1039/c5fo01256b.CrossRef Mueller, M., D. Weinmann, S. Toegel, W. Holzer, F.M. Unger, and H. Viernstein. 2016. Compounds from Caesalpinia sappan with anti-inflammatory properties in macrophages and chondrocytes. Food & Function 7 (3): 1671–1679. doi:10.​1039/​c5fo01256b.CrossRef
35.
go back to reference Jayakumar, T., C.C. Chang, S.L. Lin, Y.K. Huang, C.M. Hu, A.R. Elizebeth, S.C. Lin, and C.S. Choy. 2014. Brazilin ameliorates high glucose-induced vascular inflammation via inhibiting ROS and CAMs production in human umbilical vein endothelial cells. BioMed Research International 2014: 403703. doi:10.1155/2014/403703.CrossRefPubMedPubMedCentral Jayakumar, T., C.C. Chang, S.L. Lin, Y.K. Huang, C.M. Hu, A.R. Elizebeth, S.C. Lin, and C.S. Choy. 2014. Brazilin ameliorates high glucose-induced vascular inflammation via inhibiting ROS and CAMs production in human umbilical vein endothelial cells. BioMed Research International 2014: 403703. doi:10.​1155/​2014/​403703.CrossRefPubMedPubMedCentral
36.
Metadata
Title
Brazilin Ameliorates Diabetic Nephropathy and Inflammation in db/db Mice
Authors
Zhan-yuan Li
Yu Zheng
Yan Chen
Min Pan
Shu-bei Zheng
Wen Huang
Zhi-hong Zhou
Han-yang Ye
Publication date
01-08-2017
Publisher
Springer US
Published in
Inflammation / Issue 4/2017
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-017-0579-4

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