CN: 32-1845/R
ISSN: 2095-6975
Cite this paper:
WANG Han-Qing, WANG Sha-Sha, Chiufai Kuok, WANG Qi, CHENG Xiao-Lan. Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway[J]. Chinese Journal of Natural Medicines, 2019, 17(5): 346-354

Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway

WANG Han-Qing1, WANG Sha-Sha2, Chiufai Kuok3, WANG Qi4, CHENG Xiao-Lan5
1 College of Pharmacy, Ningxia Medical University, Yinchuan 750004, China;
2 School of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, China;
3 School of Health Sciences, Macao Polytechnic Institute, Macao SAR 999078, China;
4 Nanjing Dorra Pharmaceutical Co., Ltd., Nanjing 210012, China;
5 Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China
Diabetic nephropathy (DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae (Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin (STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated with Umb (20, 40 mg·kg-1) or irbesartan (15 mg·kg-1) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides (TG) and total cholesterol (TC) were measured by commercial assay kits, respectively. Histopathological changes and inflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine, and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β). These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.
Key words:    Diabetic nephropathy    Umbelliferone    Streptozotocin    Inflammation    TLR/NF-κB pathway   
Received: 2019-12-17   Revised:
PDF (3745 KB) Free
Print this page
Email this article to others
Articles by WANG Han-Qing
Articles by WANG Sha-Sha
Articles by Chiufai Kuok
Articles by WANG Qi
Articles by CHENG Xiao-Lan
[1] Chen T, Gao J, Xiang P, et al. Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance[J]. Int Immunopharmacol, 2015, 26(2):338-348.
[2] He Z, King GL. Microvascular complications of diabetes[J]. Endocrinol Metab Clin, 2004, 33(1):215-238.
[3] Doi T, Mima A, Matsubara T, et al. The current clinical problems for early phase of diabetic nephropathy and approach for pathogenesis of diabetic nephropathy[J]. Diabetes Res Clin Pract, 2008, 82(Suppl 1):21-24.
[4] Fernandes SM, Cordeiro PM, Watanabe M, et al. The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats[J]. Arch Endocrinol Metab, 2016, 60(5):443-449.
[5] Ang L, Yuguang L, Liying W, et al. Ergosterol alleviates kidney injury in streptozotocin-induced diabetic mice[J]. Evid-based Compl Alt Med, 2015, 2015:691594.
[6] Mora C, Navarro JF. Inflammation and pathogenesis of diabetic nephropathy[J]. Metab Clin Exp, 2004, 53(2):265-266.
[7] Dong X, Swaminathan S, Bachman LA, et al. Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury[J]. Kidney Int, 2007, 71(7):619-628.
[8] Koike N, Takamura T, Kaneko S. Induction of reactive oxygen species from isolated rat glomeruli by protein kinase C activation and TNF-alpha stimulation, and effects of a phosphodiesterase inhibitor[J]. Life Sci, 2007, 80(18):1721-1728.
[9] Soetikno V, Sari FR, Veeraveedu PT, et al. Curcumin ameliorates macrophage infiltration by inhibiting NF-kappaB activation and proinflammatory cytokines in streptozotocin induced-diabetic nephropathy[J]. Nutr Metab, 2011, 8(1):35.
[10] Jiang Q, Yi M, Guo Q, et al. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4- MyD88-NF-kappaB pathway[J]. Int Immunopharmacol, 2015, 29(2):370-376.
[11] Santos SH, Andrade JM, Fernandes LR, et al. Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet[J]. Peptides, 2013, 46:47-52.
[12] Devaraj S, Tobias P, Kasinath BS, et al. Knockout of toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy[J]. Arterioscler Thromb Vasc Biol, 2011, 31(8):1796-1804.
[13] Devaraj S, Tobias P, Jialal I. Knockout of toll-like receptor-4 attenuates the pro-inflammatory state of diabetes[J]. Cytokine, 2011, 55(3):441-445.
[14] Lin M, Yiu WH, Wu HJ, et al. Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy[J]. J Am Soc Nephrol, 2012, 23(1):86-102.
[15] Islam MN, Ran JC, Jin SE, et al. Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva[J]. J Ethnopharmacol, 2012, 144(1):175-181.
[16] Chunhua M, Lingdong K, Hongyan L, et al. Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced mice via RIP140/NF-kappaB pathway[J]. IUBMB life, 2017, 69(9):767.
[17] Luo F, Zhou R, Lei H, et al. Umbelliferone attenuates lipopolysaccharide-induced acute lung injury linked with regulation of TLRs-MyD88 and RIP140/NF-κB signaling pathways[J]. RSC Adv, 2016, 6:97503-97511.
[18] Naowaboot J, Somparn N, Saentaweesuk S, et al. Umbelliferone improves an impaired glucose and lipid metabolism in high-fat diet/streptozotocin-Induced type 2 diabetic rats[J]. Phytother Res, 2015, 29(9):1388-1395.
[19] Garud MS, Kulkarni YA. Attenuation of renal damage in type I diabetic rats by umbelliferone-a coumarin derivative[J]. Pharmacol Rep, 2017, 69(6):1263-1269.
[20] Tunçdemir M, Öztürk M. Regulation of the Ku70 and apoptosis-related proteins in experimental diabetic nephropathy[J]. Metabolism, 2016, 65(10):1466-1477.
[21] Chang B, Chen W, Zhang Y, et al. Tripterygium wilfordii mitigates hyperglycemia-induced upregulated Wnt/β-catenin expression and kidney injury in diabetic rats[J]. Exp Ther Med, 2018, 15(4):3874-3882.
[22] Li PB, Lin WL, Wang YG, et al. Antidiabetic activities of oligosaccharides of Ophiopogonis japonicus in experimental type 2 diabetic rats[J]. Int J Biol Macromol, 2012, 51:749-755.
[23] Adams GG, Imran S, Wang S, et al. The hypoglycaemic effect of pumpkins as anti-diabetic and functional medicines[J]. Food Res Int, 2011, 44(4):862-867.
[24] Dey A, Lakshmanan J. The role of antioxidants and other agents in alleviating hyperglycemia mediated oxidative stress and injury in liver[J]. Food Funct, 2013, 4(8):1148-1184.
[25] Dixit Y, Kar A. Protective role of three vegetable peels in alloxan induced diabetes mellitus in male mice[J]. Plant Foods Hum Nutr, 2010, 65(3):284-289.
[26] Feng Y, Yang S, Ma Y, et al. Role of Toll-like receptors in diabetic renal lesions in a miniature pig model[J]. Sci Adv, 2015, 1(5):e1400183.
[27] Zhang W, Zhao L, Su SQ, et al. Total glucosides of paeony attenuate renal tubulointerstitial injury in STZ-induced diabetic rats:Role of Toll-like receptor 2[J]. J Pharmacol Sci, 2014, 125(1):59-67.
[28] Kaur H, Chien A, Jialal I. Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells:Relevance to diabetic nephropathy[J]. Am J Physiol-Renal Physiol, 2012, 303(8):F1145-1150.
[29] Devaraj S, Tobias P, Kasinath BS, et al. Knockout of Toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy[J]. Arterioscl Throm Vas Biol, 2011, 31(8):1796-1804.
[30] Li F, Yang N, Zhang L, et al. Increased expression of Toll-like receptor 2 in rat diabetic nephropathy[J]. Am J Nephrol, 2010, 32(20):179-186.
[31] Lin M, Yiu WH, Li RX, et al. The TLR4 antagonist CRX-526 protects against advanced diabetic nephropathy[J]. Kidney Int, 2013, 83(5):887-900.
[32] Ramu R, Shirahatti PS, Nanjunda Swamy S, et al. Assessment of in vivo antidiabetic properties of umbelliferone and lupeol constituents of banana (Musa sp. var. nanjangud rasa bale) flower in hyperglycaemic rodent model[J]. PLoS One, 2016, 11(7):e0160048.