An antivitamin B6, 4'-methoxypyridoxine, from the seed of Ginkgo biloba L.

Wada, Keiji; Ishigaki, Seikou; Ueda, Kaori; Sakata, Masakatsu; Haga, Masanobu

doi:10.1248/cpb.33.3555

Cited by 70 publications

(63 citation statements)

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“…In the GBS analyzed by Wada et al, 4) 100 mg of free MPN was found per gram of dried material, whereas the mean amount detected in the present study was about twice that amount. By region, the mean MPN content in GBS collected in Osaka was significantly (pϭ0.05) greater than that in other regions of Japan, and thus there may be differences in MPN content depending on the provenance.…”

Section: Application 1: Mpn Determination In the Serum Of Patients Wicontrasting

confidence: 73%

“…In eight major market areas of Japan where GBS are gathered, Asahikawa, Aomori, Niigata, Nagano, Tokyo, Osaka, Okayama, and Fukuoka, we purchased GBS harvested locally and conducted separate analyses of 10 from each region. We used Wada et al's method 4) for pretreatment of the seeds. Specifically, after drying the shelled seeds for 7 d in a dryer at 40°C, we pulverized them in a mixer.…”

Section: Methodsmentioning

confidence: 99%

“…3) For a long time the agent responsible for the intoxication could not be identified, but it was finally revealed by the work of Wada et al 4) to be 4-O-methylpyridoxine (MPN). MPN competitively inhibits the action of vitamin B 6 , which is a coenzyme in the body's amino acid metabolism.…”

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confidence: 99%

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Rapid Analysis of 4-O-Methylpyridoxine in the Serum of Patients with Ginkgo Biloba Seed Poisoning by Ion-Pair High-Performance Liquid Chromatography

Hori

Fujisawa

Shimada

et al. 2004

Biological & Pharmaceutical Bulletin

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Ginkgo biloba seeds (GBS) have from ancient times been consumed in China and Japan for medicinal purposes or as food, but toxic symptoms appear if the intake of these seeds is too great. During the food shortage in Japan after the Second World War, there were many cases of toxicosis and even reports of deaths due to consumption of the seeds. Since then, there have been few such cases of poisoning, but recently some cases have occurred, mainly in children. 1,2) The principal symptoms of poisoning due to GBS are vomiting and clonic or tonic convulsions, which can at first easily be misdiagnosed as symptoms of epilepsy. The convulsions appear between 1 and 12 h after ingestion of the seeds, and in many cases attacks occur repeatedly. 3) For a long time the agent responsible for the intoxication could not be identified, but it was finally revealed by the work of Wada et al. 4) to be 4-O-methylpyridoxine (MPN). MPN competitively inhibits the action of vitamin B 6 , which is a coenzyme in the body's amino acid metabolism. Among its properties is that by inhibiting glutamate decarboxylase it inhibits the production of g-aminobutyric acid (GABA), which is an inhibitory neurotransmitter, in the brain; it is thought that it initiates convulsive attacks as a result of a relative increase in the level of glutamate, which is an excitatory neurotransmitter. 5) The pharmacokinetics of MPN in humans are not yet clearly understood, but we were interested in determining whether it was possible to predict the increase in severity of GBS poisoning from the concentration of MPN in patients' serum and from the time elapsed since the seeds were consumed. Our reasoning was that, if early prediction of severity were possible, it would also be possible to plan, on a scientific basis, the administration of preparations of the anticonvulsant diazepam and the specific MPN antagonist pyridoxal phosphate to treat recurrent convulsions. 3) The methods of determining MPN levels in the serum that have so far been reported comprise that of Yagi et al. 6) which is a reverse-phase HPLC technique using fluorescence detection; our own methods of reverse-phase HPLC using UV detection, 7) and GC/MS analysis. 8) However, since all these procedures require solid-phase extraction, it was considered that a faster method of analysis would be useful to improve the treatment approach in the clinical setting.In the present study, after simply deproteinizing serum MPN, we introduced it directly onto the HPLC column using an ion-pair reagent in the mobile phase, and thus tested the new method for rapid separation and quantitation on an ODS column. In addition, we applied the method in the analysis of the sera of 5 patients who had ingested GBS and experienced convulsions. Further, GBS were collected from the main regions of Japan where they are sold, and we investigated whether the method could be employed for the determination of MPN in GBS. MATERIALS AND METHODSChemicals and Solutions MPN was synthesized by the method described by Harris. 9) The purity of th...

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Section: Application 1: Mpn Determination In the Serum Of Patients Wicontrasting

confidence: 73%

Section: Methodsmentioning

confidence: 99%

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Rapid Analysis of 4-O-Methylpyridoxine in the Serum of Patients with Ginkgo Biloba Seed Poisoning by Ion-Pair High-Performance Liquid Chromatography

Hori

Fujisawa

Shimada

et al. 2004

Biological & Pharmaceutical Bulletin

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“…In Japan, to solve the odor problem caused by ginkgo fruit, all the ginkgo trees were replaced with other trees. However, the pollen from the male trees during the flowering season has to be removed every year to prevent bronchial diseases, such as allergies and rhinitis [1][2] (Wada et al, 1985;Singh et al, 2008). Symptoms, such as vomiting and spasms, are also caused by ginkgo seeds and street pollution reduces the daily quality of life [3][4][5] (Yamaguchi, 1977; Jung& Rho, 2010; Kajiyama et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Influence of Enzymatic Agents on the Ginkgo Fruit Ratio using Nano-Processing Technology

Lee¹,

Lee²,

So³

et al. 2018

International Journal of Forestry and Horticulture

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“…[34][35][36] Low levels of PLP, which is caused by a down-regulation of brain PDXK expression or by PL competitors, are correlated with epilepsy in animal models. [37,38] It has been suggested that the unexpected binding activity of (R)-roscovitine to PDXK explains some of the biological effects of the drug or dilutes its on-target effects by reducing the amount of free (R)-roscovitine that is available for the desired target interaction.…”

Section: Introductionmentioning

confidence: 99%

Off‐Target Decoding of a Multitarget Kinase Inhibitor by Chemical Proteomics

et al. 2009

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Unbiased: Chemical proteomics was used to profile compound interactions in an unbiased fashion. We present here the application of different compound-immobilization routes for decoding nonprotein kinase off-targets of the multitarget kinase inhibitor C1, which interacts with distinct compound moieties. Since the approval of the first selective tyrosine kinase inhibitor, imatinib, various drugs have been developed to target protein kinases. However, due to a high degree of structural conservation of the ATP binding site, off-target effects have been reported for several drugs. Here, we report on off-target decoding for a multitarget protein kinase inhibitor by chemical proteomics, by focusing on interactions with nonprotein kinases. We tested two different routes for the immobilization of the inhibitor on a carrier matrix, and thus identified off-targets that interact with distinct compound moieties. Besides several of the kinases known to bind to the compound, the pyridoxal kinase (PDXK), which has been described to interact with the CDK inhibitor (R)-roscovitine, was captured. The PDXK-inhibitor interaction was shown to occur at the substrate binding site rather than at the ATP binding site. In addition, carbonic anhydrase 2 (CA2) binding was demonstrated, and the determination of the IC(50) revealed an enzyme inhibition in the submicromolar range. The data demonstrate that different compound immobilization routes for chemical proteomics approaches are a valuable method to improve the knowledge about the off-target profile of a compound.

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An antivitamin B6, 4'-methoxypyridoxine, from the seed of Ginkgo biloba L.

Cited by 70 publications

References 1 publication

Rapid Analysis of 4-O-Methylpyridoxine in the Serum of Patients with Ginkgo Biloba Seed Poisoning by Ion-Pair High-Performance Liquid Chromatography

Rapid Analysis of 4-O-Methylpyridoxine in the Serum of Patients with Ginkgo Biloba Seed Poisoning by Ion-Pair High-Performance Liquid Chromatography

Influence of Enzymatic Agents on the Ginkgo Fruit Ratio using Nano-Processing Technology

Off‐Target Decoding of a Multitarget Kinase Inhibitor by Chemical Proteomics

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