DOI QR코드

DOI QR Code

Protective Effect of Kaempferol on Cultured Neuroglial Cells Damaged by Induction of Ischemia-like Condition

  • Son, Young-Woo (Sanbon Hospital, School of Medicine, Wonkwang University) ;
  • Choi, Yu-Ran (Department of Physical Therapy, Graduate School of Daejeon University) ;
  • Seo, Young-Mi (Department of Nursing, College of Medicine, Seonam University)
  • Received : 2017.11.22
  • Accepted : 2017.12.19
  • Published : 2017.12.31

Abstract

This study was performed to evaluate the cytotoxicity induced by ischemia-like condition (ILC) in cultured neuroglial cells (C6 glioma cells). The protective effect of kaempferol (KAE), flavonoid against the cytotoxicity induced by ILC induction was assessed. In addition, antioxidative effects of KAE were done by colorimetric assays. Cell viability and the antioxidative effects such as DPPH-radical scavenging activity, superoxide dismutase (SOD)-like activity and inhibitory activity of lipid peroxidation (LP) were analyzed. ILC induction decreased cell viability in a dose-dependent manner, and the $XTT_{90}$ value (low cytotoxicity value) and $XTT_{50}$ value (high cytotoxicity value) were determined during ILC induction for 15 and 40 minutes, respectively. The butylated hydroxytoluene (BHT) antioxidant significantly increased cell viability damaged by the ILC-induced cytotoxicity. In the protective effect of KAE on ILC-induced cytotoxicity, KAE protected the ILC-induced cytotoxicity by the significant increase of cell viability, and also it showed DPPH-radical scavenging ability, SOD-like ability and inhibitory ability of LP. From these results, it is suggested that ILC induction showed cytotoxicity in these cultures and the oxidative stress is involved in the ILC-induced cytotoxicity. While, KAE prevented ILC-induced cytotoxicity by antioxidative effects. In conclusion, natural products like KAE may be a putative therapeutic agent for the treatment of disease associated with oxidative stress such as ischemia.

Keywords

Acknowledgement

Supported by : 원광대학교

References

  1. Blois MS. Antioxidant determination by the use of a stable free radical. Nature. 1958. 26: 1199-1200.
  2. EI-Sayed NH, Omara NM, Yousef AK, Farag AM, Mabry TJ. Kaempferol triosides from Reseda muricata. Phytochem. 2001. 57: 575-578. https://doi.org/10.1016/S0031-9422(00)00479-9
  3. Endoh M, Maiese K, Wanger J. Expression of the inducible form of nitric oxide synthase by reactive astrocytes after transient global ischemia. Brain Research. 1994. 651: 92-100. https://doi.org/10.1016/0006-8993(94)90683-1
  4. Gates MA, Tworoger SS, Hecht JL, De Vivo I, Rosner B, Hankinson SE. A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer. International Journal of Cancer. 2007. 121: 2225-2232. https://doi.org/10.1002/ijc.22790
  5. Gracia-Lopez D, Cuevas MJ, Almar M, Lima E, De Paz JA, Gonzalez-Gallego J. Effects of eccentric exercise on NF-${\kappa}B$ activation in blood mononuclear cells. Medicine & Science in Sports & Exercise. 2007. 39: 653-664. https://doi.org/10.1249/mss.0b013e31802f04f6
  6. Hah DS, Kim CH, Kim GS, Kim EG, Kim JS. Antioxidant effects of traditional medicinal plants on lipid peroxidation. Korean Journal of Veterinary Research. 2005. 45: 341-350.
  7. Hamsten A, Eriksson P, Karpe F, Silveria A. Relationships of thrombosis and fibrinolysis to atherosclerosis. Current Opinion in Lipidology. 1994. 5: 382-389. https://doi.org/10.1097/00041433-199410000-00011
  8. Jialal I, Devaraj S. Low-density lipoprotein oxidation, antioxidants, and atherosclerosis: a clinical biochemistry perspective. Clinical Chemistry. 1996. 42: 498-506.
  9. Jung IJ. The effect of NMDA/glycin receptor antagonist, 7-chlorokynurenic acid on cultured astrocytes damaged by ischemialike condition. Journal of Experimental & Biomedical Sciences. 2009. 15: 355-362.
  10. Kikuzaki H, Nakatani N. Antioxidant effects of some ginger constituents. 1993. Journal of Food Science. 58: 1407-1410. https://doi.org/10.1111/j.1365-2621.1993.tb06194.x
  11. Kim MS, Seo YM, Park ST. Antioxidant effect of kaempferol on cultured human skin fibroblasts damaged by methylmercuric chloride. Journal of Plants People and Environment. 2010. 13:23-29.
  12. Kim TY, Jekal SJ. Antioxidative effect of Chelidonium majus extract on cultured NIH3T3 fibroblasts injured by cadmium chloride of toxicant. Korean Journal of Clinical Laboratory Science. 2016. 48: 1-7. https://doi.org/10.15324/kjcls.2016.48.1.1
  13. Krizkova L, Nagy M, Polonyi J, Dobias J, Belicova A, Grancai D, Krajcovic J. Phenolic acids inhibit chloroplast mutagenesis in Euglena gracilis. Mutation Research. 2000. 469: 107-114. https://doi.org/10.1016/S1383-5718(00)00059-0
  14. Lee JC, Cho GS, Choi BO, Kim HC, Kim YS, Kim WK. Intracerebral hemorrhage-induced brain injury is aggravated in a senescence accelerated prone mouse. Stroke. 2006. 37: 216-222. https://doi.org/10.1161/01.STR.0000195151.46926.7b
  15. Lee JC, Cho GS, Kim HJ, Lim JH, Oh YK. Nam WW, Chung JH, Kim WK. Accelerated cerebral ischemic injury by activated macrophage/microglia after lipopolysaccharide microinjection into at corpus callosum. Glia. 2005. 50: 168-181. https://doi.org/10.1002/glia.20164
  16. Lee JC, Kim WK. Aging and stroke. Journal of Korean Gerontological Nursing. 2006. 16: 11-16.
  17. Leung HWC, Lin CJ, Hour MJ, Yang WH, Wang MY, Lee HZ. Kaempferol induces apoptosis in human lung non-small carcinoma cells accompanied by an induction of antioxidant enzyme. Food and Chemical Toxicology. 2007. 45: 2005-2013. https://doi.org/10.1016/j.fct.2007.04.023
  18. Li YL, Gan GP, Zhang HZ, Wu HZ, Li CL, Hung YP, Liu TW, Liu JW. A flavonoid glycoside isolated from Smilax china L. rhizome in vitro anticancer effects on human cancer cell lines. Journal of Ethnopharmacology. 2007. 113: 115-124. https://doi.org/10.1016/j.jep.2007.05.016
  19. Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, Mobius-Winkler S, Schbert A, Schuler G, Hambrecht R. Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation. 2005. 111: 1763-1770. https://doi.org/10.1161/01.CIR.0000165503.08661.E5
  20. Luscher TF, Vanhoutte PM, Boulanger C. Endothelial dysfunction in hypertension, in Rubanyi G (ed): Cardiovascular significance of endothelium-derived vasoactive factors. Future New York. 1991. 20: 199-221.
  21. Ma J, Luo XD, Protiva P, Yang H, Ma C, Basile MJ, Weinstein IB, Kennelly EJ. Bioactive novel polyphenols from the fruit of Manikara zapota (Sapodolla). Journal of Natural Products. 2003. 66: 983-986. https://doi.org/10.1021/np020576x
  22. Marklund S, Marklund G. Involvement of superoxide anion radical in the oxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry. 1974. 47:468-474.
  23. Oh YL, Choi YR, Chang BS, Jung IJ. Antioxidative effect of Portulaca oleracea L. extract on allergic contact dermatitis agent, copper in cultured human skin fibroblasts. Journal of Investigative Cosmetology. 2012. 8: 243-249. https://doi.org/10.15810/jic.2012.8.4.004
  24. Pellegrini-Giampietro DE, Cherici G, Alesiani M, Carla V, Moroni F. Excitatory amino acid and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. Journal of Neuroscience. 1990. 10: 1035-1041. https://doi.org/10.1523/JNEUROSCI.10-03-01035.1990
  25. Schwartz SM, Foy L, Bowen-Pope DF, Ross R. Derivation and properties of platelet-derived growth factor-independent rat smooth muscle cells. American Journal of Pathology. 1990. 136: 1417-1428.
  26. Sellke FW, Armstrong ML, Harrison DG. Endothelium-dependent vascular relaxation is abnormal in the coronary microcirculation of atherosclerotic primates. Circulation Research. 1990. 81:1586-1593. https://doi.org/10.1161/01.CIR.81.5.1586
  27. Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathology. 2000. 10: 113-126.
  28. Verbeuren TJ, Jordaens FH, Zonnekeyn LL. Effect of hypercholesterolemia on vascular reactivity in the rabbit. I. endotheliumdependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolemic rabbits. Circulation Research. 1986. 58: 552-564. https://doi.org/10.1161/01.RES.58.4.552
  29. Wang L, Tu YC, Lian TW, Hung JT, Yen JH, Wu MJ. Distinctive antioxidant and antiinflammatory effects of flavonols. Journal of Agricultural and Food Chemistry. 2006. 54: 9798-9804. https://doi.org/10.1021/jf0620719