Mori cortex prevents kidney damage through inhibiting expression of inflammatory factors in the glomerulus in streptozocin-induced diabetic rats

Document Type: Original Article


1 Runliang Diabetes Laboratory, Diabetes Research Center, Ningbo University. Ningbo, Zhejiang, PR China

2 Department of Prevention and Health, Changhai Hospital, Second Military Medical University, Shanghai, PR China

3 Department of Nephrology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, Zhejiang, PR China

4 Center for Pharmacogenetics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA


Objective(s): It has been widely reported that Mori cortex extract (MCE) is used for the treatment of diabetes mellitus in traditional medicine. The present study was designed to investigate its mechanism of action in the treatment of diabetic nephropathy (DN). We assessed whether MCE preventive treatment ameliorates kidney damage in high-fat diet and streptozotocin (STZ)-induced type 2 diabetic rats.
Materials and Methods: Rats were fed a high-fat diet and injected with STZ. MCE was given to rats daily at 10 g/kg. Fasting blood glucose (FBG) and postprandial plasma glucose were measured. Blood and urine biochemical parameters, renal tissue morphology, and inflammation were investigated.
Results: Prevention with MCE significantly decreased FBG and homoeostasis model assessment (HOMA) of IR (HOMA-IR) levels and increased insulin levels in diabetic rats. MCE prevention significantly decreased levels of KW/BW, BUN, Cr, and 24 hr urinary protein. MCE inhibited glomerular basement membrane thickening, tubular epithelial cell hypertrophy, and glomerular capillary dilation. MCE also prevented the disappearance of bowman’s space and renal tubular lumen and decreased collagen deposition in rat kidney. Moreover, MCE reduced the levels of inflammatory factors (MCP-1 and TNF-α) and fibrosis factors (collagen IV and fibronectin).
Conclusion: MCE prevents DN through inhibition of inflammation and fibrosis in a rat model. It might provide a safe and effective way to prevent DN.


1. Kanasaki K, Taduri G, Koya D. Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis. Front Endocrinol (Lausanne) 2013; 4:7.

2. McKnight AJ, Duffy S, Maxwell AP. Genetics of Diabetic Nephropathy: a Long Road of Discovery. Curr Diabetes Rep 2015; 15:1-11.

3. Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, et al. Prevalence of diabetes among men and women in China. N Engl J Med 2010; 362:1090-1101.

4. International Diabetes Federation website. Available at: media-events/press-releases/2015/diabetes-atlas-7th-edition.

5. Barutta F, Bruno G, Grimaldi S, Gruden G. Inflammation in diabetic nephropathy: moving toward clinical biomarkers and targets for treatment. Endocrine 2015; 48:730-742.

6. Kim MJ, Lim Y. Protective effect of short-term genistein supplementation on the early stage in diabetes-induced renal damage. Mediators Inflamm 2013; 2013:510212.

7. Izquierdo MC, Sanz AB, Sanchez-Nino MD, Perez-Gomez MV, Ruiz-Ortega M, Poveda J, et al. Acute kidney injury transcriptomics unveils a relationship between inflammation and ageing. Nefrologia 2012; 32:715-723.

8. Donadelli R, Abbate M, Zanchi C, Corna D, Tomasoni S, Benigni A, et al. Protein traffic activates NF-kB gene signaling and promotes MCP-1-dependent interstitial inflammation. Am J Kidney Dis 2000; 36:1226-1241.

9. Zygner W, Gojska-Zygner O, Baska P, Dlugosz E. Increased concentration of serum TNF alpha and its correlations with arterial blood pressure and indices of renal damage in dogs infected with Babesia canis. Parasitol Res 2014; 113:1499-1503.

10. 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. Life Sci 2007; 80:1721-1728.

11. Boyle JJ, Weissberg PL, Bennett MR. Tumor necrosis factor-alpha promotes macrophage-induced vascular smooth muscle cell apoptosis by direct and autocrine mechanisms. Arterioscler Thromb Vasc Biol 2003; 23:1553-1558.

12. Wang XX, Edelstein MH, Gafter U, Qiu L, Luo Y, Dobrinskikh E, et al. G Protein-coupled bile acid receptor TGR5 activation inhibits kidney disease in obesity and Diabetes. J Am Soc Nephrol 2016; 27:1362-1378.

13. Hewitson TD. Renal tubulointerstitial fibrosis: common but never simple. Am J Physiol Renal Physiol 2009; 296:F1239-1244.

14. Martinez J, Chalupowicz DG, Roush RK, Sheth A, Barsigian C. Transglutaminase-mediated processing of fibronectin by endothelial cell monolayers. Biochemistry 1994; 33:2538-2545.

15. Lin M, Wang H, Ruan C, Xing J, Wang J, Li Y, et al. Adsorption force of fibronectin on various surface chemistries and its vital role in osteoblast adhesion. Biomacromolecules 2015; 16:973-984.

16. Kalkreuth RH, Kruger JP, Lau S, Niemeyer P, Endres M, Kreuz PC, et al. Fibronectin stimulates migration and proliferation, but not chondrogenic differentiation of human subchondral progenitor cells. Regen Med 2014; 9:759-773.

17. Zhang M, Chen M, Zhang HQ, Sun S, Xia B, Wu FH. In vivo hypoglycemic effects of phenolics from the root bark of Morus alba. Fitoterapia 2009; 80:475-477.

18. Qi SZ, Li N, Tuo ZD, Li JL, Xing SS, Li BB, et al. Effects of Morus root bark extract and active constituents on blood lipids in hyperlipidemia rats. J Ethnopharmacol 2016; 180:54-59.

19. Singab AN, El-Beshbishy HA, Yonekawa M, Nomura T, Fukai T. Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats. J Ethnopharmacol 2005; 100:333-338.

20. Ma ST, Zhang XK, Wang QL. [Experimental study on the preventive and treatment function of cortex mori for peripheral nervous lesion at the early stage of diabetes rats]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2008; 24:201-204.

21. Sugano M, Yamato H, Hayashi T, Ochiai H, Kakuchi J, Goto S, et al. High-fat diet in low-dose-streptozotocin-treated heminephrectomized rats induces all features of human type 2 diabetic nephropathy: a new rat model of diabetic nephropathy. Nutr Metab Cardiovasc Dis 2006; 16:477-484.

22. Zhang M, Lv XY, Li J, Xu ZG, Chen L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp Diabetes Res 2008; 2008:704045.

23. Amann B, Tinzmann R, Angelkort B. ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1. Diabetes Care 2003; 26:2421-2425.

24. Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TN, Salant DJ, et al. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J Exp Med 1997; 185:1371-1380.

25. Zhu XY, Chade AR, Krier JD, Daghini E, Lavi R, Guglielmotti A, et al. The chemokine monocyte chemoattractant protein-1 contributes to renal dysfunction in swine renovascular hypertension. J Hypertens 2009; 27:2063-2073.

26. Tesch GH. MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol 2008; 294:F697-701.

27. Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Rollin BJ, Tesch GH. Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice. Kidney Int 2006; 69:73-80.

28. Chow FY, Nikolic-Paterson DJ, Ma FY, Ozols E, Rollins BJ, Tesch GH. Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice. Diabetologia 2007; 50:471-480.

29. Giunti S, Tesch GH, Pinach S, Burt DJ, Cooper ME, Cavallo-Perin P, et al. Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells. Diabetologia 2008; 51:198-207.

30. Kalantarinia K, Awad AS, Siragy HM. Urinary and renal interstitial concentrations of TNF-alpha increase prior to the rise in albuminuria in diabetic rats. Kidney Int 2003; 64:1208-1213.

31. Moriwaki Y, Inokuchi T, Yamamoto A, Ka T, Tsutsumi Z, Takahashi S, et al. Effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats. Acta Diabetol 2007; 44:215-218.

32. Xu X, Qi X, Shao Y, Li Y, Fu X, Feng S, et al. Blockade of TGF-β-activated kinase 1 prevents advanced glycation end products-induced inflammatory response in macrophages. Cytokine 2016; 78:62-68.

33. Xie X, Xia W, Fei X, Xu Q, Yang X, Qiu D, et al. Relaxin Inhibits High Glucose-induced matrix accumulation in human mesangial cells by interfering with TGF-beta1 production and mesangial cells phenotypic pransition. Biol Pharm Bull 2015; 38:1464-1469.