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Neuroprotection by extract of Petasites japonicus leaves, a traditional vegetable, against oxidative stress in brain of mice challenged with kainic acid

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Summary

Background

Reactive oxygen radicals have been implicated in the pathophysiology of many neurologic disorders and brain dysfunctions. Kainic acid has been used as a model agent for the study of neurotoxicity of various excitatory amino acids, since it induces neuronal damage through excessive production of reactive oxygen species. Petasites japonicus MAX (butterbur), cultivated as culinary vegetables in Eastern Asia, contains various kinds of phenolic compounds as well as sesquiterpenes, such as petasin. In European countries, the extracts from roots of Petasites species have been used in the therapy of headache or asthma.

Aim of the study

The objective of our study is to examine the neuroprotective action of the Petasites japonicus MAX (butterbur) extract against oxidative damage in the brain of mice treated with kainic acid.

Methods

Male ICR mice, 6–8 weeks of age, were administered orally the butanol fraction from methanol extract of Petasites japonicus (BMP) or its subfraction (BMP–I or BMP–II) for 5 consecutive days. Thirty min after the final administration, the animals were challenged s. c. with kainic acid (45 mg/kg), and neurobehavioral activities were monitored. In addition, biomarkers of oxidative stress and neuronal loss in the hippocampus for the biochemical, neurobehavioral,morphological evaluations were analyzed 2 days after the kainic acid challenge.

Results

During 5–day treatment with BMP or BMP–1, the body weight gain was not significantly different from that of vehicle– treated control animals. Administration of kainic acid alone induced severe epileptiform seizures, causing a lethality of approximately 50%, and injuries of pyramidal cells in the hippocampus of mice which survived the challenge. Kainic acid exposure also resulted in a remarkable decrease in total glutathione level and glutathione peroxidase activity, and an increase in the thiobarbituric acid–reactive substance (TBARS) value in brain tissues. In comparison, coadministration with BMP (400 mg/kg) reduced the 54% lethality of mice, administered with kainic acid alone, to 25 % (P <0.05). Moreover, BMP at the same dose restored the levels of reduced glutathione and TBARS to control values (P <0.05). In further studies, BMP–I (200 mg/kg) ameliorated significantly (P <0.05) the kainic acid–induced behavioral signs, such as seizure activity, and all mice administered with BMP–I (200 mg/kg) survived the kainic acid toxicity. Consistent with the above, the administration with BMP–1 remarkably attenuated the neurobehavioral signs and neuronal loss in hippocampal CA1 and CA3 regions.

Conclusion

On the basis of these results, the butanol fraction, especially BMP–I, of Petasites japonicus MAX extract is possibly suggested to be a functional agent to prevent oxidative damage in the brain of mice.

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Abbreviations

BMP:

butanol fraction of methanol extract from Petasites japonicus MAX

GSH:

reduced glutathione

KA:

kainic acid

TBARS:

thiobarbituric acid–reactive substances

DTNB:

5.5'–dithiobis (nitrobenzoate)

References

  1. Sperk G (1994) Kainic acid seizures in the rat. Prog Neurobiol 42:1–32

    Article  CAS  Google Scholar 

  2. Olney JW, Rhee V, Ho OL (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 77:507–512

    Article  CAS  Google Scholar 

  3. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262:689–695

    CAS  Google Scholar 

  4. Floreani M, Skape, DS, Facci L, Lipartiti M, Giusti P (1997) Melatonin maintains glutathione homeostasis in kainic acidexposed rat tissues. Fed Am Soc Exp Biol J 11:1309–1315

    CAS  Google Scholar 

  5. Saija A, Princi P, Pisani A, Lanza M, Scalese M, Aramnejad E, Cesarani R, Costa G (1997) Protective effect of glutathione on kainic acid–induced neuropathological changes in rat brain. Gen Pharmacol 25:97–102

    Google Scholar 

  6. Alams JD Jr, Klaidman LK, Odunze IN, Shen HC, Miller CA (1991) Alzheimer’s disease and Parkinson’s disease, brain levels of glutathione, glutathione disulfide, and vitamin E. Mol Chem Neuropathol 14:213–225

    Google Scholar 

  7. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760

    Article  CAS  Google Scholar 

  8. Sian J, Dexter DT, Lees AJ, Daniel S, Agid Y, Javoyagid F, Jenner P, Marsden CD (1994) Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 36:348–355

    CAS  Google Scholar 

  9. Meister A (1995) Strategies for increasing cellular glutathione. In: Packer L, Cardenas E (eds) Biothiols in Health and Disease. Dekker Press, New York, NY, pp 165–188

  10. Gilgun–Shrki Y, Melamed E, Offen D (2001) Oxidative stress–induced neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 40:959–975

    Google Scholar 

  11. Hur JY, Soh Y, Kim B–H, Suk K, Sohn NW, Kim HC, Kwon HC, Lee KR, Kim SY (2001) Neuroprotective and neurotrophic effects of quinic acids fromAster scaber in PC12 cells. Biol Pharm Bull 24:921–924

    Article  CAS  Google Scholar 

  12. Lee K–J, Sok D–E, Kim Y–B, Kim MR (2002) Protective effect of vegetable extracts on oxidative stress in brain of mice administered with NMDA. Food Res Int 35:55–63

    CAS  Google Scholar 

  13. Matsuura H, Amano M, Kawabata J, Mizutani J (2002) Isolation and measurement of quercetin glucosides in flower buds of Japanese butterbur (Petasites japonicus subsp. gigantea Kitam. ). Biosci Biotechnol Biochem 66:1571–1575

    CAS  Google Scholar 

  14. Mizushina Y, Ishidoh T, Kamisuki S, Nakazawa S, Takemura M, Sugawara F, Yoshida H, Sakaguchi K (2003) Flavonoid glycoside: a new inhibitor of eukaryotic DNA polymerase α and a new carrier for inhibitor–affinity chromatography. Biochem Biophys Res Comm 301:480–487

    Article  CAS  Google Scholar 

  15. Debrenner B, Meier B (1998) Petasites hybridus: a tool for interdisciplinary research in phytotherapy. Pharm Acta Helv 72:359–380

    Google Scholar 

  16. Wang GJ, Shum AY, Lin YL, Liao JF, Wu XC, Ren J, Chen CF (2001) Calcium channel blockade in vascular smooth muscle cell is major hypotensive mechanism of S–petasin, a hypotensive sesquiterpene from Petasites formosanus. J Pharmacol Exp Ther 297:240–246

    CAS  Google Scholar 

  17. Brattstrom A (2003) A newly developed extract (Ze 339) from butterbur (Petasites hybridus L. ) is clinically efficient in allergic rhinitis (hay fever). Phytomedicine 10:50–52

    Google Scholar 

  18. Hirono I, Mori H, Yamada K, Hirata Y, Haga M (1997) Carcinogenic activity of petasitenine, a new pyrrolizidine alkaloid isolated from Petasites japonicus Maxim. J Natl Cancer Inst 58:1155–1157

    Google Scholar 

  19. Hasa Y, Tazaki H (2004) Biosynthesis of fukinolic acid isolated from Petasites japonicus. Biosci Biotechnol Biochem 68:2212–2214

    Article  CAS  Google Scholar 

  20. Lin C–H, Li C–Y, Wu T–S (2004) A novel phenylpropenoyl sulfonic acid and a new chlorophyll from the leaves of Petasites formosanus Kitamura. Chem Pharm Bull 52:1151–1152

    CAS  Google Scholar 

  21. Sok DE, Oh SH, Kim Y–B, Kim MR (2003) Neuroprotective effect of Aster scaber butanol fraction against oxidative stress in the brain of mice challenged with kainic acid. J Agric Food Chem 51:4570–4575

    Article  CAS  Google Scholar 

  22. NIH (1985) Committee on care and use of laboratory animals, National Research Council. Guide for care and use of laboratory animals, National Institute of Health Publication No. 85–23

  23. Kirkby RD, Carroll DM, Grossman AB, Subramaniam S (1996) Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents. Epilepsy Res 24:91–100

    CAS  Google Scholar 

  24. Kondo T, Sharp FR, Honkaniemi J, Mikawa S, Epstein CJ, Chan PH (1997) DNA fragmentation and prolonged expression of c–fos, c–jun, and hsp 70 in kainic acid–induced neuronal cell death in transgenic mice overexpressing human Cu Zu–superoxide dismutase. J Cereb Blood Flow and Metab 17:241–256

    CAS  Google Scholar 

  25. Schauwecker PE, Steward O (1997) Genetic determinants of susceptibility to excitotoxic cell death: Implications for gene targeting approaches. Proc Natl Acad Sci USA 94:4103–4108

    Article  CAS  Google Scholar 

  26. Tan D, Manchester LC, Reiter RJ, Qi W, Kim SJ, El–Sokkary GH (1998) Melatonin protects hippocampal neurons in vivo against kainic acid–induced damage in mice. J Neurosc Res 54:382–389

    CAS  Google Scholar 

  27. Kim HC, Moon KD, Oh SY, Kim SP, Lee SR (2001) Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid–induced neuronal damage in the mouse hippocampus. Neurosci Lett 314:65–68

    Article  CAS  Google Scholar 

  28. Bidlack WT, Tappel AL (1973) Damage to microsomal membrane by lipid peroxidation. Lipids 8:177–182

    CAS  Google Scholar 

  29. Roberts JC, Francetic DJ (1993) The importance of sample preparation and storage in glutathione determination analysis. Anal Biochem 211:183–187

    CAS  Google Scholar 

  30. Raymond C, Rahma BH, Georges D (1995) Dietary polyunsaturated Fatty Acids and aging modulate glutathionerelated antioxidants in rat liver. J Nutr 125:3062–3070

    Google Scholar 

  31. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254

    Article  CAS  Google Scholar 

  32. SAS (1997) SAS user's Guide. Statistics version 6. 12, Cary, NC: SAS Institute Inc

  33. Steel RGD, Torrie JH (1960) Principle and Procedures of Statistics. McGraw– Hill, New York, NY

  34. Kirkby RD, Forbes RA, Subramaniam S (1996) Modification of kainate–induced behavioral and electrographic seizures following inhibition of nitric oxide synthase in mice. Epilepsy Res 24:79–90

    CAS  Google Scholar 

  35. Reiter RJ (1995) Oxidative processes and antioxidative defense mechanism in the aging brain. Fed Am Soc Exp Biol J 9:526–533

    CAS  Google Scholar 

  36. Thomet OAR, Wiesmann UN, Schapowal A, Bizer C, Simon H–U (2001) Role of petasin in the potential anti–inflammatory activity of a plant extract of Petasites hybridus. Biochem Pharmacol 61:1041–1047

    Article  CAS  Google Scholar 

  37. Iriye R, Furukawa K, Nishida R, Kim C, Fkami H (1992) Isolation and synthesis of a new bio–antimutagen, petasiphenol, from scapes of Petasites japonicum. Biosci Biotech Biochem 56:1773–1775

    CAS  Google Scholar 

  38. Kim SR, Park MJ, Lee M, Sung SH, Park EJ, Kim J, Kim SY, Oh TH, Markelonis GJ, Kim YJ (2002) Flavonoids of Inula britannica protect cultured cortical cells from necrotic cell death induced by glutamate. Free Rad Biol Med 32:596–604

    CAS  Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, Daejeon, Korea

    D.–E. Sok

  2. Dept. of Food and Nutrition, Chungnam National University, 220 Gung–Dong, Yuseong–Gu, Daejeon 305-764, Korea

    S. H. Oh &  M. R. Kim Ph.D.

  3. College of Veterinary Science and Research, Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Korea

    Y.–B. Kim & H.–G. Kang

Authors
  1. D.–E. Sok
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  2. S. H. Oh
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  4. H.–G. Kang
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  5. M. R. Kim Ph.D.
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Correspondence to M. R. Kim Ph.D..

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Sok, D., Oh, S.H., Kim, Y. et al. Neuroprotection by extract of Petasites japonicus leaves, a traditional vegetable, against oxidative stress in brain of mice challenged with kainic acid. Eur J Nutr 45, 61–69 (2006). https://doi.org/10.1007/s00394-005-0565-8

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  • DOI: https://doi.org/10.1007/s00394-005-0565-8

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