Brazilin Ameliorates Diabetic Nephropathy and Inflammation in Db/db Mice

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2017 May 13

PMID 28497277

Citations 5

Authors

Zhan-Yuan Li

Yu Zheng

Yan Chen

Min Pan

Shu-Bei Zheng

Wen Huang

Zhi-Hong Zhou

Han-Yang Ye

Affiliations

Soon will be listed here.

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.

Citing Articles

Regulation of cellular and molecular markers of epithelial-mesenchymal transition by Brazilin in breast cancer cells.

Cayetano-Salazar L, Hernandez-Moreno J, Bello-Martinez J, Olea-Flores M, Castaneda-Saucedo E, Ramirez M PeerJ. 2024; 12:e17360.

PMID: 38737746 PMC: 11088821. DOI: 10.7717/peerj.17360.

Brazilin is a natural product inhibitor of the NLRP3 inflammasome.

McMahon E, El-Sayed S, Green J, Hoyle C, FitzPatrick L, Jones E iScience. 2024; 27(2):108968.

PMID: 38327788 PMC: 10847679. DOI: 10.1016/j.isci.2024.108968.

PC-1 NF suppresses high glucose-stimulated inflammation and extracellular matrix accumulation in glomerular mesangial cells via the Wnt/β-catenin signaling.

Xiao L, Chen Y, Yuan Y, Xu B, Gao Q, Chen P Exp Ther Med. 2019; 18(3):2029-2036.

PMID: 31410160 PMC: 6676197. DOI: 10.3892/etm.2019.7793.

Correlation of the severity of chronic kidney disease with serum inflammation, osteoporosis and vitamin D deficiency.

Liu C, Li H Exp Ther Med. 2019; 17(1):368-372.

PMID: 30651805 PMC: 6307476. DOI: 10.3892/etm.2018.6916.

Curcumin attenuates high glucose-induced inflammatory injury through the reactive oxygen species-phosphoinositide 3-kinase/protein kinase B-nuclear factor-κB signaling pathway in rat thoracic aorta endothelial cells.

Zhang Z, Li K J Diabetes Investig. 2017; 9(4):731-740.

PMID: 29080256 PMC: 6031518. DOI: 10.1111/jdi.12767.

References

Nirmal N, Panichayupakaranant P . Anti-Propionibacterium acnes assay-guided purification of brazilin and preparation of brazilin rich extract from Caesalpinia sappan heartwood. Pharm Biol. 2014; 52(9):1204-7. DOI: 10.3109/13880209.2014.884607. View

Huang X, Kitching A, Tipping P, Holdsworth S . Interleukin-10 inhibits macrophage-induced glomerular injury. J Am Soc Nephrol. 2000; 11(2):262-269. DOI: 10.1681/ASN.V112262. View

Kolati S, Kasala E, Bodduluru L, Mahareddy J, Uppulapu S, Gogoi R . BAY 11-7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-κB pathway. Environ Toxicol Pharmacol. 2015; 39(2):690-9. DOI: 10.1016/j.etap.2015.01.019. View

Lee H, Kang S, Byun H, Jeon J, Park K, Kang K . Brazilin Limits Inflammatory Responses through Induction of Prosurvival Autophagy in Rheumatoid Fibroblast-Like Synoviocytes. PLoS One. 2015; 10(8):e0136122. PMC: 4546660. DOI: 10.1371/journal.pone.0136122. View

Tucker P, Scanlan A, Dalbo V . Chronic kidney disease influences multiple systems: describing the relationship between oxidative stress, inflammation, kidney damage, and concomitant disease. Oxid Med Cell Longev. 2015; 2015:806358. PMC: 4377508. DOI: 10.1155/2015/806358. View

Jia Y, Zhao J, Liu M, Li B, Song Y, Li Y . Brazilin exerts protective effects against renal ischemia-reperfusion injury by inhibiting the NF-κB signaling pathway. Int J Mol Med. 2016; 38(1):210-6. PMC: 4899020. DOI: 10.3892/ijmm.2016.2616. View

Bohle A, Wehrmann M, Bogenschutz O, Batz C, Muller C, Muller G . The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. Pathol Res Pract. 1991; 187(2-3):251-9. DOI: 10.1016/s0344-0338(11)80780-6. View

Zhang Q, Liu J, Qi X, Qi C, Yu Q . Inhibitory activities of Lignum Sappan extractives on growth and growth-related signaling of tumor cells. Chin J Nat Med. 2014; 12(8):607-12. DOI: 10.1016/S1875-5364(14)60092-3. View

Klessens C, Zandbergen M, Wolterbeek R, Bruijn J, Rabelink T, Bajema I . Macrophages in diabetic nephropathy in patients with type 2 diabetes. Nephrol Dial Transplant. 2016; 32(8):1322-1329. DOI: 10.1093/ndt/gfw260. View

10.

Khil L, Cheon A, Chang T, Moon C . Effects of calcium on brazilin-induced glucose transport in isolated rat epididymal adipocytes. Biochem Pharmacol. 1997; 54(1):97-101. DOI: 10.1016/s0006-2952(97)00145-7. View

11.

Navarro-Gonzalez J, Mora-Fernandez C, de Fuentes M, Chahin J, Mendez M, Gallego E . Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Am Soc Nephrol. 2014; 26(1):220-9. PMC: 4279740. DOI: 10.1681/ASN.2014010012. View

12.

Kim Y, Park C . New therapeutic agents in diabetic nephropathy. Korean J Intern Med. 2017; 32(1):11-25. PMC: 5214729. DOI: 10.3904/kjim.2016.174. View

13.

Moon C, Lee S, Lee M, Kim S . Effects of Brazilin on glucose oxidation, lipogenesis and therein involved enzymes in adipose tissues from diabetic KK-mice. Life Sci. 1993; 53(16):1291-7. DOI: 10.1016/0024-3205(93)90574-m. View

14.

Navarro-Gonzalez J, Mora-Fernandez C, de Fuentes M, Garcia-Perez J . Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011; 7(6):327-40. DOI: 10.1038/nrneph.2011.51. View

15.

Khil L, Han S, Kim S, Chang T, Jeon S, So D . Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes. Biochem Pharmacol. 1999; 58(11):1705-12. DOI: 10.1016/s0006-2952(99)00275-0. View

16.

Gao X, Wang T, Zhang Z, Cao Y, Zhang N, Guo M . Brazilin plays an anti-inflammatory role with regulating Toll-like receptor 2 and TLR 2 downstream pathways in Staphylococcus aureus-induced mastitis in mice. Int Immunopharmacol. 2015; 27(1):130-7. DOI: 10.1016/j.intimp.2015.04.043. View

17.

Satriano J . Kidney growth, hypertrophy and the unifying mechanism of diabetic complications. Amino Acids. 2007; 33(2):331-9. DOI: 10.1007/s00726-007-0529-9. View

18.

Giunti S, Tesch G, Pinach S, Burt D, Cooper M, Cavallo-Perin P . Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells. Diabetologia. 2007; 51(1):198-207. DOI: 10.1007/s00125-007-0837-3. View

19.

Qian Y, Feldman E, Pennathur S, Kretzler M, Brosius 3rd F . From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes. 2008; 57(6):1439-45. PMC: 4239998. DOI: 10.2337/db08-0061. View

20.

Gembardt F, Bartaun C, Jarzebska N, Mayoux E, Todorov V, Hohenstein B . The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. Am J Physiol Renal Physiol. 2014; 307(3):F317-25. DOI: 10.1152/ajprenal.00145.2014. View