Abstract
Purpose
The anti-glycative and anti-oxidative effects from Houttuynia cordata leaves aqueous extract (HCAE) in heart and kidney of diabetic mice were examined.
Methods
HCAE, at 1 or 2 %, was supplied in drinking water for 8 weeks. Plasma glucose and blood urea nitrogen (BUN) levels and creatine phosphokinase (CPK) activity were measured. The production of oxidative and inflammatory factors was determined. Activity and protein expression of associated enzymes or regulators were analyzed.
Results
HCAE intake at both doses lowered plasma glucose and BUN levels, and CPK activity and also restored creatinine clearance rate in diabetic mice. HCAE intake, only at 2 %, retained plasma insulin levels (P < 0.05). HCAE reduced reactive oxygen species, protein carbonyl, interleukin-6, tumor necrosis factor-alpha, N ε-(carboxymethyl)-lysine, pentosidine and fructose levels, and reserved glutathione content in heart and kidney of diabetic mice (P < 0.05). Diabetes enhanced aldose reductase (AR) activity and protein expression in heart and kidney (P < 0.05). HCAE intake at both doses decreased renal AR activity and protein expression, but only at 2 % lowered cardiac AR activity and protein expression (P < 0.05). Diabetes increased protein expression of RAGE, p47phox and gp91phox, nuclear factor kappa-B (NF-κB) p50, NF-κB p65 and mitogen-activated protein kinase in heart and kidney (P < 0.05). HCAE intake only at 2 % limited RAGE expression, but at 1 and 2 % downregulated p47phox, NF-κB p65 and p-p38 expression in these organs (P < 0.05).
Conclusions
These findings suggest that Houttuynia cordata leaves aqueous extract could ameliorate cardiac and renal injury under diabetic condition.
Similar content being viewed by others
Abbreviations
- AGEs:
-
Advanced glycation endproducts
- AR:
-
Aldose reductase
- BUN:
-
Blood urea nitrogen
- CCr:
-
Creatinine clearance rate
- CML:
-
N ε-(carboxymethyl)-lysine
- CPK:
-
Creatine phosphokinase
- Cr:
-
Creatinine
- DCFH-DA:
-
2′,7′-Dichlorofluorescein diacetate
- DNP:
-
Dinitrophenylhydrazine
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- GSH:
-
Glutathione
- HCAE:
-
Houttuynia cordata leaves aqueous extract
- IL:
-
Interleukin
- MAPK:
-
Mitogen-activated protein kinase
- NF-κB:
-
Nuclear factor kappa-B
- RFU:
-
Relative fluorescence unit
- ROS:
-
Reactive oxygen species
- TNF-alpha:
-
Tumor necrosis factor-alpha
References
Dunlop M (2000) Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int Suppl 77:S3–S12
Chung SS, Ho EC, Lam KS, Chung SK (2003) Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol 14:S233–S236
Peyroux J, Sternberg M (2006) Advanced glycation endproducts (AGEs): pharmacological inhibition in diabetes. Pathol Biol 54:405–419
Vlassara H, Striker GE (2013) Advanced glycation endproducts in diabetes and diabetic complications. Endocrinol Metab Clin North Am 42:697–719
Hirata K, Kubo K (2004) Relationship between blood levels of N-carboxymethyl-lysine and pentosidine and the severity of microangiopathy in type 2 diabetes. Endocr J 51:537–544
Ghanem AA, Elewa A, Arafa LF (2011) Pentosidine and N-carboxymethyl-lysine: biomarkers for type 2 diabetic retinopathy. Eur J Ophthalmol 21:48–54
Barlovic DP, Thomas MC, Jandeleit-Dahm K (2010) Cardiovascular disease: what’s all the AGE/RAGE about? Cardiovasc Hematol Disord Drug Targets 10:7–15
Xie J, Méndez JD, Méndez-Valenzuela V, Aguilar-Hernández MM (2013) Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell Signal 25:2185–2197
Meng J, Leung KS, Jiang Z, Dong X, Zhao Z, Xu LJ (2005) Establishment of HPLC-DAD-MS fingerprint of fresh Houttuynia cordata. Chem Pharm Bull 53:1604–1609
Wang F, Lu F, Xu L (2007) Effects of Houttuynia cordata thumb on expression of BMP-7 and TGF-beta1 in the renal tissues of diabetic rats. J Tradit Chin Med 27:220–225
Kumar M, Prasad SK, Krishnamurthy S, Hemalatha S (2014) Antihyperglycemic activity of Houttuynia cordata Thunb. in streptozotocin-induced diabetic rats. Adv Pharm Sci 2014:809438
Guan JZ, Wang JJ, Cheng ZH, Liu Y, Li ZY (2012) Cytomixis and meiotic abnormalities during microsporogenesis are responsible for male sterility and chromosome variations in Houttuynia cordata. Genet Mol Res 11:121–130
Lin MC, Hsu PC, Yin MC (2013) Protective effects of Houttuynia cordata aqueous extract in mice consuming a high saturated fat diet. Food Funct 4:322–327
Singleton VL, Orthofer R, Lamuela-Raventos RM (1999) Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin Ciocalteu reagent. Methods Enzymol 299:152–178
Zhishen J, Mengcheng T, Jianming W (1999) The determination of flavonoid content in mulberry and their scavenging effects on superoxide radicals. Food Chem 64:555–559
Miyata T, Taneda S, Kawai R, Ueda Y, Horiuchi S, Hara M, Maeda K, Monnier VM (1996) Identification of pentosidine as a native structure for advanced glycation end products in β-2-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis. Proc Natl Acad Sci USA 93:2353–2358
Guerrant G, Moss CW (1984) Determination of monosaccharides as aldononitrile, O-methyloxime, alditol, and cyclitol acetate derivatives by gas chromatography. Anal Chem 56:633–638
Nishinaka T, Yabe-Nishimura C (2001) EGF receptor-ERK pathway is the major signaling pathway that mediates upregulation of aldose reductase expression under oxidative stress. Free Radic Biol Med 31:205–216
Fiorentino TV, Prioletta A, Zuo P, Folli F (2013) Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des 19:5695–5703
Palomer X, Salvadó L, Barroso E, Vázquez-Carrera M (2013) An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy. Int J Cardiol 168:3160–3172
Gorin Y, Block K (2013) Nox as a target for diabetic complications. Clin Sci 125:361–382
Teshima Y, Takahashi N, Nishio S, Saito S, Kondo H, Fukui A, Aoki K, Yufu K, Nakagawa M, Saikawa T (2014) Production of reactive oxygen species in the diabetic heart. Roles of mitochondria and NADPH oxidase. Circ J 78:300–306
Mukherjee TK, Mukhopadhyay S, Hoidal JR (2005) The role of reactive oxygen species in TNFalpha-dependent expression of the receptor for advanced glycation end products in human umbilical vein endothelial cells. Biochim Biophys Acta 1744:213–223
Harijith A, Ebenezer DL, Natarajan V (2014) Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol 5:352
Lieuw-A-Fa ML, van Hinsbergh VW, Teerlink T, Barto R, Twisk J, Stehouwer CD, Schalkwijk CG (2004) Increased levels of N(epsilon)-(carboxymethyl)lysine and N(epsilon)-(carboxyethyl)lysine in type 1 diabetic patients with impaired renal function: correlation with markers of endothelial dysfunction. Nephrol Dial Transplant 19:631–636
Chao PC, Huang CN, Hsu CC, Yin MC, Guo YR (2010) Association of dietary AGEs with circulating AGEs, glycated LDL, IL-1α and MCP-1 levels in type 2 diabetic patients. Eur J Nutr 49:429–434
Kaneko M, Bucciarelli L, Hwang YC, Lee L, Yan SF, Schmidt AM, Ramasamy R (2005) Aldose reductase and AGE-RAGE pathways: key players in myocardial ischemic injury. Annu N Y Acad Sci 1043:702–709
Obrosova IG, Kador PF (2011) Aldose reductase/polyol inhibitors for diabetic retinopathy. Curr Pharm Biotechnol 12:373–385
Shi L, Yu X, Yang H, Wu X (2013) Advanced glycation end products induce human corneal epithelial cells apoptosis through generation of reactive oxygen species and activation of JNK and p38 MAPK pathways. PLoS ONE 8:e66781
Fukami K, Yamagishi S, Okuda S (2014) Role of AGEs-RAGE system in cardiovascular disease. Curr Pharm Des 20:2395–2402
Kim JM, Lee EK, Kim DH, Yu BP, Chung HY (2010) Kaempferol modulates pro-inflammatory NF-kappaB activation by suppressing advanced glycation endproducts-induced NADPH oxidase. Age 32:197–208
Zang Y, Sato H, Igarashi K (2011) Anti-diabetic effects of a kaempferol glycoside-rich fraction from unripe soybean (Edamame, Glycine max L. Merrill. ‘Jindai’) leaves on KK-A(y) mice. Biosci Biotechnol Biochem 75:1677–1684
Ramar M, Manikandan B, Raman T, Priyadarsini A, Palanisamy S, Velayudam M, Munusamy A, Marimuthu PN, Vaseeharan B (2012) Protective effect of ferulic acid and resveratrol against alloxan-induced diabetes in mice. Eur J Pharmacol 690:226–235
Umadevi S, Gopi V, Elangovan V (2014) Regulatory mechanism of gallic acid against advanced glycation end products induced cardiac remodeling in experimental rats. Chem Biol Interact 208:28–36
Acknowledgments
This study was partially supported by a Grant from Ministry of Science and Technology, Taipei City, Taiwan (NSC 102-2313-B-039-002-MY3).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
There was no conflict of interest regarding this manuscript.
Additional information
An erratum to this article is available at http://dx.doi.org/10.1007/s00394-017-1463-6.
Rights and permissions
About this article
Cite this article
Hsu, Cc., Yang, Ht., Ho, Jj. et al. Houttuynia cordata aqueous extract attenuated glycative and oxidative stress in heart and kidney of diabetic mice. Eur J Nutr 55, 845–854 (2016). https://doi.org/10.1007/s00394-015-0994-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00394-015-0994-y