Neuroprotective effect of honokiol (HK), orally administered, on oxidative damage in the brain of mice challenged with N-methyl-d-aspartic acid (NMDA) was examined. HK (1–100 mg/kg) was administered to Institute of Cancer Research (ICR) male mice through a gavage for 3 days consecutively, and on the third day, NMDA (150 mg/kg) was intraperitoneally (i.p.) administered. Administration of NMDA, causing a lethality of approximately 60%, resulted in a significant decrease of total glutathione (GSH) level and increase of thiobarbituric acid-reactive substances (TBARS) value in brain tissue. Meanwhile, oral administration of HK (⩾3 mg/kg) for 3 days reduced the lethality (60%) in NMDA-treated group to 10% level, and alleviated the behavioral signs of NMDA neurotoxicity. Moreover, HK pretreatment restored the levels of total GSH and TBARS in the brain tissue to control levels (p<0.01). Additionally, GSH peroxidase activity in cytosolic portion of brain homogenate was also restored significantly (p<0.01), whereas GSH reductase activity was not. Separately, compared to vehicle-treated control, no significant changes in body and brain weight were observed in mice administered with HK. Based on these results, oral intake of HK is suggested to prevent oxidative stress in the brain of mice.

To investigate the effect of various kinds of fresh Brassica vegetables and several types of kimchi on the induction of hepatic glutathione S-transferase activity of mice, extract of fresh vegetable or kimchi was administered to ICR female mice via gavage for 5 days. Separately, volatile sulfur compounds in the extract of fresh vegetable or kimchi were analyzed by GC/MS as well as sulforaphane by GC/MS/SIM. The amount of isothiocyanates including sulforaphane decreased significantly in the extract of turnip kimchi or red cabbage kimchi, compared to that of fresh. Meanwhile there was a small decrease of sulfides in green onion kimchi where isothiocyanates were not detected. Fresh Brassica vegetables containing a higher level of sulforaphane showed higher GST induction, while onion family vegetables with higher sulfides induced higher GST activity, compared to control. Kimchi extract with a lower isothiocyanate level also induced GST activity in mice: 1.64-fold for green onion kimchi, 1.49-fold for turnip kimchi, and 1.37-fold for red cabbage kimchi. GST induction rate is affected by cultivar, processing method and administration route. Our present studies indicate that the processing of Brassica vegetables does not markedly reduce GST induction in mice.

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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Acetylcholinesterase (AChE) purified from mouse brain was reconstituted in liposomes of a different charge, and the properties of liposome-associated AChE were investigated. Relative to the Km value (38.5 μM) of AChE bound to a neutral liposome, the value of AChE reconstituted in a negatively-charged liposome decreased to 23.3 μM, whereas that of AChE in a positively-charged liposome increased to 90.9 μM. Additionally, AChE bound to a positively-charged liposome expressed a wider range of optimum pH than the enzyme in a negatively-charged liposome. In a stability study, it was found that soluble AChE was unstable at pH 5.5 and 7.4, while it was relatively stable at pH 10. Noteworthy, the immobilization of AChE to liposome enhanced the stability of soluble enzyme at acidic and neutral pH. Moreover, in the stabilization of the enzyme, a neutral liposome was more effective than charged liposomes, of which a positively-charged liposome was more effective than a negatively-charged liposome at acidic pH. Based on these results, it is proposed that while the Km value and the pH dependence of AChE activity are affected by the charge of liposome, the stability of AChE is determined mainly by a hydrophobic binding to a phospholipid membrane.

Recently, vinyl sulfones have been observed to selectively inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is an important ATP-generating enzyme in glycolysis. The possibility of using GAPDH as a biochemical parameter of cytotoxicity by vinyl sulfones was investigated using mouse lymphocytes. Incubation of lymphocyte GAPDH with ethylvinyl sulfone resulted in a pseudo-first-order loss of enzyme activity. The exposure of lymphocytes to ethylvinyl sulfone resulted in the decrease of GAPDH activity followed by ATP depletion and cell death, which were both dependent on the concentration of ethylvinyl sulfone. A further study on the time-dependent change indicated that cell death was preceded by ATP loss. Compared to ethylvinyl sulfone, divinyl sulfone was more than 8 times more potent in causing either ATP depletion or cell death.

Neurochemical effects of vemaculogen, a secondary fungal (Penicillium Verruculosum) metabolite were studied using rat synaptosomes. To evaluate the presynaptic effects of vemiculogen, high affinity uptake and potassium stimulated release, as well as spontaneous release of ³H-GABA from synaptosome enriched preparntions from the hippocampus, corpus striatum, and cerebrnl cortex were investigated. High affinity uptake of 3H-GABA into hippocampal and striatal synaptosomes decreased by 36.7 and 26.2%, respectively, in the presence of 0.1 mM vezruculogen, while ³H-GABA uptake in cerebrocortical synaptosomes showed no remarkable change. Vemiculogen had no significant effect on the spontaneous or the stimulated release of ³H-GABA from hippocampal, striatal, and cortical synaptosomes. These results suggest that verruculogen exerts presynaptic effects on GABAergic nerve terminals by inhibiting high affinity uptake systems in the hippocampus and striatum.

Differential inhibitions of soluble and membrane-bound acetylcholinesterase forms purified from mouse brain were examined by the comparison of kinetic constants such as a Km value, a Kss value (substrate inhibition constant), and IC50 values of active site-selective ligands including choline esters. Membrane-bound acetylcholinesterase form (solubilized only in the presence of detergent) showed lower Km and Kss values than soluble acetylcholinesterase form (easily solubilized without detergent). Edrophonium expressed a slightly but significantly (p < 0.01) higher inhibition of detergent-soluble acetylcholinesterase form than aqueous-soluble acetylcholinesterase form, while physostigmine inhibited both forms with a similar potency. A remarkable difference in inhibition was observed using choline esters; although choline esters with acyl chain of a short size (acetyl- to butyrylcholine) or a long size (heptanoyl- to decanoylcholine) showed a similar inhibitory potency for two forms of acetylcholinesterase, pentanoylcholine and hexanoylcholine inhibited more strongly aqueous-soluble acetylcholinesterase than detergent-soluble acetylcholinesterase. Thus, it is suggested that the two forms of AChE may be distinguished kinetically by pentanoyl- or hexanoylcholine.

AbstractAus dem Hydroperoxid (Ia) werden die Perester (Ib) und (Ic) hergestellt.

The monoacetylenic acid, 5,6-dehydroarachidonic acid (5,6-DHA), inhibits the 5-lipoxygenase in RBL-1 extracts in a time-dependent irreversible manner. In intact cell systems, 5,6-DHA is not as effective as ETYA or 15(S)-HEYA in inhibiting the 5-lipoxygenase activities, because 5,6-DHA is metabolized into triglycerides, phospholipids and hydroxylated products. While lipoxygenation of arachidonic acid at C-5 and C-12 is inhibited by 15-HETE, the transformation of arachidonic acid into 5,15-diHETE via 15-HPETE in human leukocytes is relatively insensitive to 15-HETE.