Protective effects of morroniside isolated from Corni Fructus against renal damage in streptozotocin-induced diabetic rats.

In our previous study, we reported the renoprotective effect of Hachimi-jio-gan, a Chinese traditional prescription consisting of eight medicinal plants, and also reported the effect of Corni Fructus (Cornus officinalis SIEB. et ZUCC.), a component of Hachimi-jio-gan, on diabetic nephropathy using diabetic rats. In this study, we investigated the effects of morroniside isolated from Corni Fructus on renal damage in streptozotocin-treated diabetic rats. Oral administration of morroniside at a dose of 20 or 100 mg/kg body weight/d for 20 d to diabetic rats resulted in significant decreases in increasing serum glucose and urinary protein levels. Moreover, the decreased levels of serum albumin and total protein in diabetic rats were significantly increased by morroniside administration at a dose of 100 mg/kg body weight/d. In addition, morroniside significantly reduced the elevated serum urea nitrogen level and showed a tendency to reduce creatinine clearance. Morroniside also significantly reduced the enhanced levels of serum glycosylated protein, and serum and renal thiobarbituric acid-reactive substances. Protein expressions related to the advanced glycation endproduct (AGE) level and actions, oxidative stress such as N(epsilon)-(carboxyethyl)lysine, as well as receptors for AGE and heme oxygenase-1 were increased in diabetic rats, but the levels were also significantly decreased by the administration of morroniside. This suggests that morroniside exhibits protective effects against diabetic renal damage by inhibiting hyperglycemia and oxidative stress. These results indicate that morroniside is one component partly responsible for the protective effects of Corni Fructus and Hachimi-jio-gan against diabetic renal damage.

[1]  K. Ikeda,et al.  Accumulation of Nσ-(Carboxy-methyl)lysine and Changes inGlomerular Extracellular MatrixComponents in Otsuka Long-EvansTokushima Fatty Rat:A Model of Spontaneous NIDDM , 1998, Nephron.

[2]  M. Uchiyama,et al.  Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. , 1978, Analytical biochemistry.

[3]  K. Nath Heme oxygenase-1: a provenance for cytoprotective pathways in the kidney and other tissues. , 2006, Kidney international.

[4]  R. Wolfe,et al.  The United States Renal Data System's 1991 annual data report: an introduction. , 1991, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[5]  Yan Shi,et al.  Morroniside and loganin extracted from Cornus officinalis have protective effects on rat mesangial cell proliferation exposed to advanced glycation end products by preventing oxidative stress. , 2006, Canadian journal of physiology and pharmacology.

[6]  Naotoshi Shibahara,et al.  Long‐term treatment with Hachimi‐jio‐gan attenuates kidney damage in spontaneously diabetic WBN/Kob rats , 2005, The Journal of pharmacy and pharmacology.

[7]  國郎 小笠原,et al.  Chem. Pharm. Bull.(オピニオン) , 2007 .

[8]  H. Lardy,et al.  [15] Isolation of liver or kidney mitochondria , 1967 .

[9]  L. Chiang,et al.  Chemoprevention against hepatocellular carcinoma of Cornus officinalis in vitro. , 2004, The American journal of Chinese medicine.

[10]  J. Zingraff,et al.  Can the nephrologist prevent dialysis-related amyloidosis? , 1991, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[11]  K. Kang,et al.  Beneficial effect of Corni Fructus, a constituent of Hachimi-jio-gan, on advanced glycation end-product-mediated renal injury in Streptozotocin-treated diabetic rats. , 2007, Biological & pharmaceutical bulletin.

[12]  M. Cooper,et al.  Pathophysiology of diabetic nephropathy. , 1998, Metabolism: clinical and experimental.

[13]  T. Yokozawa,et al.  Protective effect of Hachimi‐jio‐gan against renal failure in a subtotal nephrectomy rat model , 2005, The Journal of pharmacy and pharmacology.

[14]  M. Crow,et al.  Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. , 2001, Diabetes.

[15]  T. Kislinger,et al.  N ε-(Carboxymethyl)Lysine Adducts of Proteins Are Ligands for Receptor for Advanced Glycation End Products That Activate Cell Signaling Pathways and Modulate Gene Expression* , 1999, The Journal of Biological Chemistry.

[16]  V. D’Agati,et al.  Glucose , Glycation , and RAGE : Implications for Amplification of Cellular Dysfunction in Diabetic , 2003 .

[17]  You-Ping Zhu,et al.  Chinese Materia Medica: Chemistry, Pharmacology and Applications , 1998 .

[18]  Juei-Tang Cheng,et al.  Corni fructus as the major herb of Die‐Huang‐Wan for lowering plasma glucose in Wistar rats , 2004, The Journal of pharmacy and pharmacology.

[19]  S. Shenouda,et al.  Up-Regulation of Heme Oxygenase Provides Vascular Protection in an Animal Model of Diabetes through Its Antioxidant and Antiapoptotic Effects , 2006, Journal of Pharmacology and Experimental Therapeutics.

[20]  J. Twisk,et al.  Increased levels of Nϵ-(carboxymethyl)lysine and Nϵ-(carboxyethyl)lysine in type 1 diabetic patients with impaired renal function: correlation with markers of endothelial dysfunction , 2004 .

[21]  S. Horiuchi,et al.  Conventional antibody against Nε-(carboxymethyl)lysine (CML) shows cross-reaction to Nε-(carboxyethyl)lysine (CEL): Immunochemical quantification of CML with a specific antibody , 2004 .

[22]  D. Gill,et al.  A MICRO-BIURET METHOD FOR ESTIMATING PROTEINS. , 1964, Analytical biochemistry.

[23]  K. Jung,et al.  Influence of cyclosporin A on the respiration of isolated rat kidney mitochondria , 1985, FEBS letters.

[24]  T. Yokozawa,et al.  Activity of the Chinese prescription Hachimi‐jio‐gan against renal damage in the Otsuka Long‐Evans Tokushima Fatty rat: a model of human type 2 diabetes mellitus , 2006, The Journal of pharmacy and pharmacology.

[25]  Hai-Ping Hao,et al.  Effects of iridoid total glycoside from Cornus officinalis on prevention of glomerular overexpression of transforming growth factor beta 1 and matrixes in an experimental diabetes model. , 2004, Biological & pharmaceutical bulletin.

[26]  Hai-Ping Hao,et al.  Morroniside protects cultured human umbilical vein endothelial cells from damage by high ambient glucose. , 2004, Acta pharmacologica Sinica.

[27]  C. Chen,et al.  Antimicrobial effect of extracts from Chinese chive, cinnamon, and corni fructus. , 2001, Journal of agricultural and food chemistry.

[28]  T. Lyons,et al.  The Advanced Glycation End Product, N-(Carboxymethyl)lysine, Is a Product of both Lipid Peroxidation and Glycoxidation Reactions (*) , 1996, The Journal of Biological Chemistry.

[29]  Zhide Hu,et al.  Analysis of three effective components in Fructus corni and its preparations by micellar electrokinetic capillary chromatography. , 2003, Biomedical chromatography : BMC.

[30]  Nessar Ahmed,et al.  Advanced glycation endproducts--role in pathology of diabetic complications. , 2005, Diabetes research and clinical practice.

[31]  K. Isshiki,et al.  Enhancement of glomerular heme oxygenase-1 expression in diabetic rats. , 2001, Diabetes research and clinical practice.

[32]  Yusuke Suzuki,et al.  Candesartan reduced advanced glycation end-products accumulation and diminished nitro-oxidative stress in type 2 diabetic KK/Ta mice. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[33]  K. Kang,et al.  Identification of antidiabetic effect of iridoid glycosides and low molecular weight polyphenol fractions of Corni Fructus, a constituent of Hachimi-jio-gan, in streptozotocin-induced diabetic rats. , 2007, Biological & pharmaceutical bulletin.

[34]  Warszawski Uniwersytet Medyczny,et al.  Diabetes care , 2019, Health at a Glance.

[35]  C. Yabe-Nishimura,et al.  Aldose reductase in glucose toxicity: a potential target for the prevention of diabetic complications. , 1998, Pharmacological reviews.

[36]  M. Nair,et al.  Anthocyanins in Cornus alternifolia, Cornus controversa, Cornus kousa and Cornus florida fruits with health benefits. , 2006, Life sciences.

[37]  Richard Barnett Diabetes , 1904, The Lancet.

[38]  T. Okuda,et al.  Tannins of cornaceous plants. I. Cornusiins A, B and C, dimeric monomeric and trimeric hydrolyzable tannins from Cornus officinalis, and orientation of valoneoyl group in related tannins. , 1989, Chemical & pharmaceutical bulletin.

[39]  E. Cho,et al.  Protective effects of the Chinese prescription Hachimi‐jio‐gan against diabetic oxidative stress , 2004, The Journal of pharmacy and pharmacology.

[40]  G. Paolisso,et al.  Oxidative Stress and Diabetic Vascular Complications , 1996, Diabetes Care.

[41]  A. Schmidt,et al.  Pathogenesis of diabetic nephropathy: a radical approach. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.