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


OBJECTIVE
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.


CONCLUSIONS
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.
College of Pharmacy, Chungnam National University, Daejeon, Korea.
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D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D036901:Petasites / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D007608:Kainic Acid