Neuroprotective Effects of a Butanol Fraction of Rosa hybrida Petals in a Middle Cerebral Artery Occlusion Model

  • Yang, Goeun (College of Veterinary Medicine, Chungbuk National University) ;
  • Park, Dongsun (College of Veterinary Medicine, Chungbuk National University) ;
  • Lee, Sun Hee (College of Veterinary Medicine, Chungbuk National University) ;
  • Bae, Dae-Kwon (College of Veterinary Medicine, Chungbuk National University) ;
  • Yang, Yun-Hui (College of Veterinary Medicine, Chungbuk National University) ;
  • Kyung, Jangbeen (College of Veterinary Medicine, Chungbuk National University) ;
  • Kim, Dajeong (College of Veterinary Medicine, Chungbuk National University) ;
  • Choi, Ehn-Kyoung (College of Veterinary Medicine, Chungbuk National University) ;
  • Hong, Jin Tae (College of Pharmacy, Chungbuk National University) ;
  • Jeong, Heon-Sang (Department Food Science and Technology, Chungbuk National University) ;
  • Kim, Hee Jung (Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University) ;
  • Jang, Su Kil (Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University) ;
  • Joo, Seong Soo (Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University) ;
  • Kim, Yun-Bae (College of Veterinary Medicine, Chungbuk National University)
  • Received : 2013.09.02
  • Accepted : 2013.10.18
  • Published : 2013.11.30


The neuroprotective effects of a butanol fraction of white rose petal extract (WRPE-BF) were investigated in a middle cerebral artery occlusion (MCAO) model. Seven week-old male rats were orally administered WRPE-BF for 2 weeks and subjected to MCAO for 2 h, followed by reperfusion. Twenty-four h later, MCAO-induced behavioral dysfunctions were markedly improved in a dose-dependent manner by pretreatment with WRPE-BF. Moreover, higher dose of WRPE-BF not only decreased infarction area but also effectively reduced astrogliosis. The expression of inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein in MCAO model were markedly inhibited by WRPE-BF treatment. Notably, WRPE-BF decreased nitricoxide and malondialdehyde levels in the striatum and subventricular zone of stroke-challenged brains. These data suggested that WRPE-BF may exert its neuroprotective effects via anti-oxidative and anti-inflammatory activities against ischemia-reperfusion brain injury and could be a good candidate as a therapeutic target for ischemic stroke.



  1. Asano, T., Mori, T., Shimoda, T., Shinagawa., R., Satoh, S., Yada, N., Katsumata, S., Matsuda, S., Kagamiishi, Y. and Tateishi, N. (2005) Arundic acid (ONO-2506) ameliorates delayed ischemic brain damage by preventing astrocytic overproduction of S100B. Curr. Drug Targets CNS Neurol. Disord. 4, 127-142.
  2. Callaway, J. K., Beart, P. M. and Jarrott, B. (1998) A reliable procedure for comparison of antioxidants in rat brain homogenates. J. Pharmacol. Toxicol. Methods 39, 155-162.
  3. Chan, P. H. (1996) Role of oxidants in ischemic brain damage. Stroke 27, 1124-1129.
  4. Chan, P. H. (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J. Cereb. Blood Flow Metab. 21, 2-14.
  5. Cho, E. J., Yokozawa, T., Rhyu, D. Y., Kim, S. L., Shibahara, N. and Park, J. C. (2003) Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1,1-diphenyl-2-picrylhydrazyl radical. Phytomedicine 10, 544-551.
  6. Choi, B. I., Park, D., Lee, S. H., Bae, D. K., Yang, G., Yang, Y. H., Kim, T. K., Choi, E. K., Lee, H. J., Choi, K. C., Nahm, S. S. and Kim, Y. B. (2012) Neurobehavioral defi cits correlate with the cerebral infarction volume of stroke animals: a comparative study on ischemia-reperfusion and photothrombosis models. Environ. Toxicol. Pharmacol. 33, 60-69.
  7. Clark, W. M., Rinker, L. G., Lessov, N. S., Lowery, S. L. and Cipolla, M. J. (2001) Efficacy of antioxidant therapies in transient focal ischemia in mice. Stroke 32, 1000-1004.
  8. Collaço-Moraes, Y., Aspey, B., Harrison, M. and de Belleroche, J. (1996) Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia. J. Cereb. Blood Flow Metab. 16, 1366-1372.
  9. Iadecola, C. and Alexander, M. (2001) Cerebral ischemia and infl ammation. Curr. Opin. Neurol. 14, 89-94.
  10. Iadecola, C., Zhang, F., Casey, R., Nagayama, M. and Ross, M. E. (1997) Delayed reduction of ischemic brain injury and neurological deficits in mice lacking the inducible nitric oxide synthase gene. J. Neurosci. 17, 9157-9164.
  11. Jeon, J. H., Kwon, S-C., Park, D. S., Shin, S., Jeong, J. H., Park, S. Y., Hwang, S. Y., Kim, Y. B. and Joo, S. S. (2009) Anti-allergic effects of white rose pertal extract and anti-atopic properties of its hexane fraction. Arch. Pharm. Res. 32, 823-830.
  12. Joo, S. S., Kim, Y. B. and Lee, D. I. (2010) Antimicrobial and antioxidant properties of secondary metabolites from white rose flower. Plant Pathol. J. 26, 57-62.
  13. Kondo, K., Kurihara, M., Miyata, N., Suzuki, T. and Toyoda, M. (1999) Scavenging mechanisms of (-)-epigallocatechin gallate and (-)-epicatechin gallate on peroxyl radicals and formation of superoxide during the inhibitory action. Free Radic. Biol. Med. 27, 855-863.
  14. Lakhan, S. E., Kirchgessner, A. and Hofer, M. (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J. Transl. Med. 7, 97.
  15. Lee, H. J., Kim, H. S., Kim, S. T., Park, D., Hong, J. T., Kim, Y. B. and Joo, S. S. (2011) Anti-inflammatory effects of hexane fraction from white rose flower extracts via inhibition of inflammatory repertoires. Biomol. Ther. 19, 331-335.
  16. Longa, E. Z., Weinstein, P. R., Carlson, S. and Cummins, R. (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20, 84-91.
  17. Margaill, I., Plotkine, M. and Lerouet, D. (2005) Antioxidant strategies in the treatment of stroke. Free Radic. Biol. Med. 39, 429-443.
  18. Mohammadi, M. T., Shid-Moosavi, S. M. and Dehghani, G. A. (2012) Contribution of nitric oxide synthase (NOS) in blood-brain barrier disruption during acute focal cerebral ischemia in normal rat. Pathophysiology 19, 13-20.
  19. Mojsilovic-Petrovic, J., Callaghan, D., Cui, H., Dean, C., Stanimirovic, D. B. and Zhang, W. (2007) Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes. J. Neuroinflammation 4, 12.
  20. Ng, T. B., Gao, W., Li, L., Niu, S. M., Zhao, L., Liu, J., Shi, L. S., Fu, M. and Liu, F. (2005) Rose (Rosa rugosa)-flower extract increases the activities of antioxidant enzymes and their gene expression and reduces lipid peroxidation. Biochem. Cell Biol. 83, 78-85.
  21. Nicolis, E., Lampronti, I., Dechecchi, M. C., Borgatti, M., Tamanini, A., Bianchi, N., Bezzerri, V., Mancini, I., Giri, M. G., Rizzotti, P., Gambari, R. and Cabrini, G. (2008) Pyrogallol, an active compound from the medicinal plant Emblica offi cinalis, regulates expression of pro-inflammatory genes in bronchial epithelial cells. Int. Immunopharmacol. 8, 1672-1680.
  22. Nogawa, S., Forster, C., Zhang, F., Nagayama, M., Ross, M. E. and Iadecola, C. (1998) Interaction between inducible nitric oxide synthase and cyclooxygenase-2 after cerebral ischemia. Proc. Natl. Acad. Sci. U.S.A. 95, 10966-10971.
  23. Nogawa, S., Zhang, F., Ross, M. E. and Iadecola, C. (1997) Cyclooxygenase-2 gene expression in neurons contributes to ischemic brain damage. J. Neurosci. 17, 2746-2755.
  24. Ohkawa, H., Ohishi, N. and Yagi, K. (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95, 351-358.
  25. Pan, H. C., Kao, T. K., Ou, Y. C., Yang, D. Y., Yen, Y. J., Wang, C. C., Chuang, Y. H., Liao, S. L., Raung, S. L., Wu, C. W., Chiang, A. N. and Chen, C. J. J. (2009) Protective effect of docosahexaenoic acid against brain injury in ischemic rats. J. Nutr. Biochem. 20, 715-725.
  26. Park, D., Jeon, J. H., Kwon, S. C., Shin, S., Jang, J. Y., Jeong, H. S., Lee, D. I., Kim, Y. B. and Joo, S. S. (2009) Antioxidative activities of white rose flower extract and pharmaceutical advantages of its hexane fraction via free radical scavenging effects. Biochem. Cell Biol. 87, 943-952.
  27. Park, D., Joo, S. S., Lee, H., Choi, K. C., Kim, S. U. and Kim, Y. B. (2012) Microtubule-associated protein 2, an early blood marker of ischemic brain injury. J. Neurosci. Res. 90, 461-467.
  28. Park, D., Lee, S. H., Choi, Y. J., Bae, D. K., Yang, Y. H., Yang, G., Kim, T. K., Yeon, S., Hwang, S. Y., Joo, S. S. and Kim, Y.B. (2011) Improving effect of silk peptides on the cognitive function of rats with aging brain facilitated by D-galactose. Biomol. Ther. 19, 224-230.
  29. Raghubir, R. (2008) Emerging role of astrocytes in cerebral ischemia/ reperfusion injury. Ann. Neurosci. 15, 17-24.
  30. Rogers, D. C. and Hunter, A. J. (1997) Photothrombotic lesions of the rat cortex impair acquisition of the water maze. Pharmacol. Biochem. Behav. 56, 747-754.
  31. Schmid-Elsaesser, R., Zausinger, S., Hungerhuber, E., Baethmann, A. and Reulen, H. J. (1998) A critical reevaluation of the intraluminal thread model of focal cerebral ischemia: evidence of inadvertent premature reperfusion and subarachnoid hemorrhage in rats by laser-Doppler flowmetry. Stroke 29, 2162-2170.
  32. Sims, N. R. and Muyderman, H. (2010) Mitochondria, oxidative metabolism and cell death in stroke. Biochim. Biophys. Acta 1802, 80-91.
  33. Thaakur, S. and Sravanthi, R. (2010) Neuroprotective effect of Spirulina in cerebral ischemia-reperfusion injury in rats. J. Neural Transm. 117, 1083-1091.
  34. Vaughan, C. J. and Delanty, N. (1999) Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 30, 1969-1973.

Cited by

  1. Antimicrobial activities of ethanol and butanol fractions of white rose petal extract vol.76, 2016,
  2. Rosa hybrida extract suppresses vascular smooth muscle cell responses by the targeting of signaling pathways, cell cycle regulation and matrix metalloproteinase-9 expression vol.37, pp.4, 2016,
  3. Effects of anti-obesity drugs, phentermine and mahuang, on the behavioral patterns in Sprague-Dawley rat model vol.30, pp.2, 2014,
  4. Dexmedetomidine Protects Mouse Brain from Ischemia-Reperfusion Injury via Inhibiting Neuronal Autophagy through Up-Regulating HIF-1α vol.11, 2017,
  5. Extraction conditions of white rose petals for the inhibition of enzymes related to skin aging vol.31, pp.3, 2015,
  6. Modulation of Mitochondrial Function and Autophagy Mediates Carnosine Neuroprotection Against Ischemic Brain Damage vol.45, pp.8, 2014,
  7. The Ethanol Fraction of White Rose Petal Extract Abrogates Excitotoxicity-Induced Neuronal Damage In Vivo and In Vitro through Inhibition of Oxidative Stress and Proinflammation vol.10, pp.10, 2018,
  8. Effects of Snake Venom Pharmacopuncture on a Mouse model of Cerebral Infarction vol.36, pp.3, 2013,