Planta Med 2008; 74(2): 114-119
DOI: 10.1055/s-2008-1034277
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

A Phytochemically Characterized Extract of Cordyceps militaris and Cordycepin Protect Hippocampal Neurons from Ischemic Injury in Gerbils

In Koo Hwang1 [*] , Soon Sung Lim2 [*] , Ki-Yeon Yoo3 , Yeon Sil Lee2 , Ho Gyoung Kim4 , Il-Jun Kang5 , Hyung Joo Kwon6 , Jinseu Park7 , Soo Young Choi7 , Moo-Ho Won3
  • 1Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea
  • 2Regional Innovation Center, Hallym University, Chuncheon, South Korea
  • 3Department of Anatomy and Neurobiology, Institute of Neurodegeneration and Regeneration, College of Medicine, Hallym University, Chuncheon, South Korea
  • 4Mushtech Co. Ltd, Chuncheon, South Korea
  • 5Department of Food Science and Nutrition, Hallym University, Chuncheon, South Korea
  • 6Department of Microbiology, College of Medicine, Hallym University, Chuncheon, South Korea
  • 7Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, South Korea
Weitere Informationen

Publikationsverlauf

Received: April 12, 2007 Revised: April 12, 2007

Accepted: December 3, 2007

Publikationsdatum:
23. Januar 2008 (online)

Abstract

In the present study, we investigated effects of the dried, hot-water extract of Cordyceps militaris (CME) and its major metabolite (cordycepin) against ischemic damage. The repeated treatment with CME protected hippocampal CA1 pyramidal neurons from ischemic damage in gerbils. The treatment with CME or cordycepin in gerbils reduced 4-hydroxy-2-nonenal (a marker of lipid peroxidation) immunoreactivity and levels in the ischemic CA1 region. Glial fibrillary acidic protein immunoreactive astrocytes and ionized calcium-binding adapter molecule 1 immunoreactive microglia in the vehicle-treated ischemic group were activated in the CA1 region 4 days after ischemia/reperfusion, whereas in the CME- or cordycepin-treated ischemic group, their activation was significantly decreased. These results suggest that the repeated treatment with CME protects against neuronal damage from ischemia/reperfusion by reducing oxidative damage.

Abbreviations

CME:Cordyceps militaris water extract

CV:cresyl violet

GFAP:glial fibrillary acidic protein

HNE:4-hydroxy-2-nonenal

HPLC:high performance liquid chromatography

Iba-1:ionized calcium-binding adapter molecule 1

ROD:relative optical density

ROS:reactive oxygen species

References

  • 1 Rigano D, Grassia A, Borrelli F, Aviello G, Piozzi F, Bruno M. et al . Phytochemical and pharmacological studies on the acetonic extract of Marrubium globosum ssp. libanoticum. .  Planta Med. 2006;  72 575-8
  • 2 Gobbo-Neto L, Santos M D, Kanashiro A, Almeida M C, Lucisano-Valim Y M, Lopes J L. et al . Evaluation of the anti-inflammatory and antioxidant activities of di-C-glucoflavones from Lychnophora ericoides (Asteraceae).  Planta Med. 2005;  71 3-6
  • 3 Eastwood M A. Interaction of dietary antioxidants in vivo: how fruit and vegetables prevent disease?.  QJM. 1999;  92 527-30
  • 4 Wang B J, Won S J, Yu Z R, Su C L. Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide.  Food Chem Toxicol. 2005;  43 543-52
  • 5 Wu J Y, Zhang Q X, Leung P H. Inhibitory effects of ethyl acetate extract of Cordyceps sinensis mycelium on various cancer cells in culture and B16 melanoma in C57BL/6 mice.  Phytomedicine. 2007;  14 43-9
  • 6 Nan J X, Park E J, Yang B K, Song C H, Ko G, Sohn D H. Antifibrotic effect of extracellular biopolymer from submerged mycelial cultures of Cordyceps militaris on liver fibrosis induced by bile duct ligation and scission in rats.  Arch Pharm Res. 2001;  24 327-32
  • 7 Zhao-Long W, Xiao-Xia W, Wei-Ying C. Inhibitory effect of Cordyceps sinensis and Cordyceps militaris on human glomerular mesangial cell proliferation induced by naïve LDL.  Cell Biochem Funct. 2000;  18 93-7
  • 8 Kodama E N, McCaffrey R P, Yusa K, Mitsuya H. Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells.  Biochem Pharmacol. 2000;  59 273-81
  • 9 Nakamura H, Katsumata T, Nishiyama Y, Otori T, Katsura K, Katayama Y. Effect of ischemic preconditioning on cerebral blood flow after subsequent lethal ischemia in gerbils.  Life Sci. 2006;  78 1713-9
  • 10 Hwang I K, Yoo K Y, Kim D S, Jeong Y K, Kim J D, Shin H K. et al . Neuroprotective effects of grape seed extract on neuronal injury by inhibiting DNA damage in the gerbil hippocampus after transient forebrain ischemia.  Life Sci. 2004;  75 1989-2001
  • 11 Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia.  Brain Res. 1992;  239 57-69
  • 12 Lin C S, Polsky K, Nadler J V, Crain B J. Selective neocortical and thalamic cell death in the gerbil after transient ischemia.  Neuroscience. 1990;  35 289-99
  • 13 Gotz M E, Kunig G, Riederer P, Youdim M B. Oxidative stress: free radical production in neural degeneration.  Pharmacol Ther. 1994;  63 37-122
  • 14 Chen J, Zhang W, Lu T, Li J, Zheng Y, Kong L. Morphological and genetic characterization of a cultivated Cordyceps sinensis fungus and its polysaccharide component possessing antioxidant property in H22 tumor-bearing mice.  Life Sci. 2006;  78 2742-8
  • 15 McKracken E, Graham D I, Nilsen M, Stewart J, Nicoll J A, Horsburgh K. 4-Hydroxynonenal immunoreactivity is increased in human hippocampus after global ischemia.  Brain Pathol. 2004;  11 414-21
  • 16 Wang Q, Tompkins K D, Simonyi A, Korthuis R J, Sun A Y, Sun G Y. Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus.  Brain Res. 2006;  1090 182-9
  • 17 Hwang I K, Yoo K Y, Kim D H, Lee B H, Kwon Y G, Won M H. Time course of changes in pyridoxal 5’-phosphate (vitamin B6 active form) and its neuroprotection in experimental ischemic damage.  Exp Neurol. 2007;  206 114-25
  • 18 Guo F Q, Li A, Huang L F, Liang Y Z, Liang Y Z, Chen B M. Identification and determination of nucleosides in Cordyceps sinensis and its substitutes by high performance liquid chromatography with mass spectrometric detection.  J Pharm Biomed Anal. 2006;  40 623-30
  • 19 Jin D Q, Park B C, Lee J S, Choi H D, Lee Y S, Yang J H. et al . Mycelial extract of Cordyceps ophioglossoides prevents neuronal cell death and ameliorates beta-amyloid peptide-induced memory deficits in rats.  Biol Pharm Bull. 2004;  27 1126-9
  • 20 Yamaguchi Y, Kagota S, Nakamura K, Shinozuka K, Kunitomo M. Inhibitory effects of water extracts from fruiting bodies of cultured Cordyceps sinensis on raised serum lipid peroxide levels and aortic cholesterol deposition in atherosclerotic mice.  Phytother Res. 2000;  14 650-2
  • 21 Yu H M, Wang B S, Huang S C, Duh P D. Comparison of protective effects between cultured Cordyceps militaris and natural Cordyceps sinensis against oxidative damage.  J Agric Food Chem. 2006;  54 3132-8
  • 22 Shahed A R, Kim S I, Shoskes D A. Down-regulation of apoptotic and inflammatory genes by Cordyceps sinensis extract in rat kidney following ischemia/reperfusion.  Transplant Proc. 2001;  33 2986-7
  • 23 Wang J Y, Wen L L, Huang Y N, Chen Y T, Ku M C. Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation.  Curr Pharm Des. 2006;  12 3521-33

1 In Koo Hwang and Soon Sung Lim contributed equally to this article

Prof. Moo-Ho Won

Department of Anatomy and Neurobiology

College of Medicine

Hallym University

Chuncheon 200-702

South Korea

Telefon: +82-33-248-2522

Fax: +82-33-256-1614

eMail: mhwon@hallym.ac.kr