Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves
The effects of Ginkgo biloba leaf extract on rat brain or livermonoamine oxidase (MAO)‐A and ‐B activity, biogenic amine concentration in nervous tissue, N‐methyl‐d‐aspartate (NMDA)‐ and N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP‐4)‐induced neurotoxicity and antioxidant activity was investiga...
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| creator | SLOLEY, B. D. URICHUK, L. J. MORLEY, P. DURKIN, J. SHAN, J. J. PANG, P. K. T. COUTTS, R. T. |
| description | The effects of Ginkgo biloba leaf extract on rat brain or livermonoamine oxidase (MAO)‐A and ‐B activity, biogenic amine concentration in nervous tissue, N‐methyl‐d‐aspartate (NMDA)‐ and N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP‐4)‐induced neurotoxicity and antioxidant activity was investigated to determine the effects of the extract on monoamine catabolism and neuroprotection.
Ginkgo biloba leaf extract was shown to produce in‐vitro inhibition of rat brain MAO‐A and ‐B. The Ginkgo biloba extract was chromatographed on a reverse‐phase HPLC system and two of the components isolated were shown to be MAO inhibitors (MAOIs). These MAOIs were identified by high‐resolution mass spectrometry as kaempferol and isorhamnetin. Pure kaempferol and a number of related flavonoids were examined as MAOIs in‐vitro. Kaempferol, apigenin and chrysin proved to be potent MAOIs, but produced more pronounced inhibition of MAO‐A than MAO‐B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO‐A were 7 times 10−7, 1 times 10−6 and 2 times 10−6 m, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex‐vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid. Kaempferol was shown to protect against NMDA‐induced neuronal toxicity in‐vitro in rat cortical cultures, but did not prevent DSP‐4‐induced noradrenergic neurotoxicity in an in‐vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid‐peroxidation assay.
This data indicates that the MAO‐inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability. |
| doi_str_mv | 10.1211/0022357001774075 |
| format | Article |
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Ginkgo biloba leaf extract was shown to produce in‐vitro inhibition of rat brain MAO‐A and ‐B. The Ginkgo biloba extract was chromatographed on a reverse‐phase HPLC system and two of the components isolated were shown to be MAO inhibitors (MAOIs). These MAOIs were identified by high‐resolution mass spectrometry as kaempferol and isorhamnetin. Pure kaempferol and a number of related flavonoids were examined as MAOIs in‐vitro. Kaempferol, apigenin and chrysin proved to be potent MAOIs, but produced more pronounced inhibition of MAO‐A than MAO‐B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO‐A were 7 times 10−7, 1 times 10−6 and 2 times 10−6 m, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex‐vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid. Kaempferol was shown to protect against NMDA‐induced neuronal toxicity in‐vitro in rat cortical cultures, but did not prevent DSP‐4‐induced noradrenergic neurotoxicity in an in‐vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid‐peroxidation assay.
This data indicates that the MAO‐inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1211/0022357001774075</identifier><identifier>PMID: 10813558</identifier><identifier>CODEN: JPPMAB</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>3,4-Dihydroxyphenylacetic Acid - metabolism ; Administration, Oral ; Animals ; Biological and medical sciences ; Brain - drug effects ; Brain - enzymology ; Brain - metabolism ; Cells, Cultured ; Chromatography, High Pressure Liquid ; Dopamine - metabolism ; Dose-Response Relationship, Drug ; Flavonoids ; General pharmacology ; Ginkgo biloba ; Ginkgo biloba - chemistry ; Hydroxyindoleacetic Acid - metabolism ; Kaempferols ; Lipid Peroxidation - drug effects ; Liver - drug effects ; Liver - enzymology ; Male ; Medical sciences ; Mice ; Monoamine Oxidase - drug effects ; Monoamine Oxidase - metabolism ; Monoamine Oxidase Inhibitors - analysis ; Monoamine Oxidase Inhibitors - pharmacology ; N-Methylaspartate - pharmacology ; Neurons - cytology ; Neurons - drug effects ; Neuropharmacology ; Neuroprotective agent ; Neuroprotective Agents - pharmacology ; Norepinephrine - metabolism ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Plant Extracts - chemistry ; Plant Extracts - pharmacology ; Plant Leaves - chemistry ; Plants, Medicinal ; Quercetin - analogs & derivatives ; Quercetin - analysis ; Quercetin - pharmacology ; Rats ; Rats, Sprague-Dawley ; Serotonin - metabolism ; Tumor Cells, Cultured - drug effects ; Tumor Cells, Cultured - metabolism</subject><ispartof>Journal of pharmacy and pharmacology, 2000-04, Vol.52 (4), p.451-459</ispartof><rights>2000 Royal Pharmaceutical Society of Great Britain</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5470-6ed7b46eb4e857ea2a86e0253a6cc5a9c58044a81bab57d953fee443156bbeeb3</citedby><cites>FETCH-LOGICAL-c5470-6ed7b46eb4e857ea2a86e0253a6cc5a9c58044a81bab57d953fee443156bbeeb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1211%2F0022357001774075$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1211%2F0022357001774075$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1335695$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10813558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SLOLEY, B. D.</creatorcontrib><creatorcontrib>URICHUK, L. J.</creatorcontrib><creatorcontrib>MORLEY, P.</creatorcontrib><creatorcontrib>DURKIN, J.</creatorcontrib><creatorcontrib>SHAN, J. J.</creatorcontrib><creatorcontrib>PANG, P. K. T.</creatorcontrib><creatorcontrib>COUTTS, R. T.</creatorcontrib><title>Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>The effects of Ginkgo biloba leaf extract on rat brain or livermonoamine oxidase (MAO)‐A and ‐B activity, biogenic amine concentration in nervous tissue, N‐methyl‐d‐aspartate (NMDA)‐ and N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP‐4)‐induced neurotoxicity and antioxidant activity was investigated to determine the effects of the extract on monoamine catabolism and neuroprotection.
Ginkgo biloba leaf extract was shown to produce in‐vitro inhibition of rat brain MAO‐A and ‐B. The Ginkgo biloba extract was chromatographed on a reverse‐phase HPLC system and two of the components isolated were shown to be MAO inhibitors (MAOIs). These MAOIs were identified by high‐resolution mass spectrometry as kaempferol and isorhamnetin. Pure kaempferol and a number of related flavonoids were examined as MAOIs in‐vitro. Kaempferol, apigenin and chrysin proved to be potent MAOIs, but produced more pronounced inhibition of MAO‐A than MAO‐B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO‐A were 7 times 10−7, 1 times 10−6 and 2 times 10−6 m, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex‐vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid. Kaempferol was shown to protect against NMDA‐induced neuronal toxicity in‐vitro in rat cortical cultures, but did not prevent DSP‐4‐induced noradrenergic neurotoxicity in an in‐vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid‐peroxidation assay.
This data indicates that the MAO‐inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability.</description><subject>3,4-Dihydroxyphenylacetic Acid - metabolism</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain - drug effects</subject><subject>Brain - enzymology</subject><subject>Brain - metabolism</subject><subject>Cells, Cultured</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Dopamine - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Flavonoids</subject><subject>General pharmacology</subject><subject>Ginkgo biloba</subject><subject>Ginkgo biloba - chemistry</subject><subject>Hydroxyindoleacetic Acid - metabolism</subject><subject>Kaempferols</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Monoamine Oxidase - drug effects</subject><subject>Monoamine Oxidase - metabolism</subject><subject>Monoamine Oxidase Inhibitors - analysis</subject><subject>Monoamine Oxidase Inhibitors - pharmacology</subject><subject>N-Methylaspartate - pharmacology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neuropharmacology</subject><subject>Neuroprotective agent</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Norepinephrine - metabolism</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. Drug treatments</subject><subject>Plant Extracts - chemistry</subject><subject>Plant Extracts - pharmacology</subject><subject>Plant Leaves - chemistry</subject><subject>Plants, Medicinal</subject><subject>Quercetin - analogs & derivatives</subject><subject>Quercetin - analysis</subject><subject>Quercetin - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Serotonin - metabolism</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Tumor Cells, Cultured - metabolism</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMFv0zAUhy0EYmVw54R8QNwy7Di20yN0W1dotyKBOEbPzguYJXaxU9ad-NdJlAoQF05P1vu-37N-hDzn7IznnL9mLM-F1IxxrQum5QMyy1mRZ5rL8iGZjets2IsT8iSlb4wxrZR6TE44K7mQspyRn6safe8aZ6F3wdPQ0PeA3a7BGFoKiQLdBB-gcx7pzcHVkJCu_FdnXB8iBV_TbejHCGjpNe5j2MXhbXvwPXWeXhz6CLZPY_DS-dsvgb51bTBA1wg_MD0ljxpoEz47zlPy6fLi4-IqW98sV4s368zKQrNMYa1NodAUWEqNkEOpkOVSgLJWwtzKkhUFlNyAkbqeS9EgFoXgUhmDaMQpeTXlDt_7vsfUV51LFtsWPIZ9qnKm-FjmALIJtDGkFLGpdtF1EO8rzqqx9Orf0gflxTF7bzqs_xKmlgfg5RGAZKFtInjr0h9OCKnmY46csDvX4v1_71bvtldbNWeDl02eSz0efnsQbyulxQB-vl5Wl9vNOT__sKkW4hf0Oajg</recordid><startdate>200004</startdate><enddate>200004</enddate><creator>SLOLEY, B. D.</creator><creator>URICHUK, L. J.</creator><creator>MORLEY, P.</creator><creator>DURKIN, J.</creator><creator>SHAN, J. J.</creator><creator>PANG, P. K. T.</creator><creator>COUTTS, R. T.</creator><general>Blackwell Publishing Ltd</general><general>Pharmaceutical Press</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>200004</creationdate><title>Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves</title><author>SLOLEY, B. D. ; URICHUK, L. J. ; MORLEY, P. ; DURKIN, J. ; SHAN, J. J. ; PANG, P. K. T. ; COUTTS, R. T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5470-6ed7b46eb4e857ea2a86e0253a6cc5a9c58044a81bab57d953fee443156bbeeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>3,4-Dihydroxyphenylacetic Acid - metabolism</topic><topic>Administration, Oral</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain - drug effects</topic><topic>Brain - enzymology</topic><topic>Brain - metabolism</topic><topic>Cells, Cultured</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Dopamine - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Flavonoids</topic><topic>General pharmacology</topic><topic>Ginkgo biloba</topic><topic>Ginkgo biloba - chemistry</topic><topic>Hydroxyindoleacetic Acid - metabolism</topic><topic>Kaempferols</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Monoamine Oxidase - drug effects</topic><topic>Monoamine Oxidase - metabolism</topic><topic>Monoamine Oxidase Inhibitors - analysis</topic><topic>Monoamine Oxidase Inhibitors - pharmacology</topic><topic>N-Methylaspartate - pharmacology</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neuropharmacology</topic><topic>Neuroprotective agent</topic><topic>Neuroprotective Agents - pharmacology</topic><topic>Norepinephrine - metabolism</topic><topic>Pharmacognosy. Homeopathy. Health food</topic><topic>Pharmacology. Drug treatments</topic><topic>Plant Extracts - chemistry</topic><topic>Plant Extracts - pharmacology</topic><topic>Plant Leaves - chemistry</topic><topic>Plants, Medicinal</topic><topic>Quercetin - analogs & derivatives</topic><topic>Quercetin - analysis</topic><topic>Quercetin - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Serotonin - metabolism</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Tumor Cells, Cultured - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SLOLEY, B. D.</creatorcontrib><creatorcontrib>URICHUK, L. J.</creatorcontrib><creatorcontrib>MORLEY, P.</creatorcontrib><creatorcontrib>DURKIN, J.</creatorcontrib><creatorcontrib>SHAN, J. J.</creatorcontrib><creatorcontrib>PANG, P. K. T.</creatorcontrib><creatorcontrib>COUTTS, R. T.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Journal of pharmacy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SLOLEY, B. D.</au><au>URICHUK, L. J.</au><au>MORLEY, P.</au><au>DURKIN, J.</au><au>SHAN, J. J.</au><au>PANG, P. K. T.</au><au>COUTTS, R. T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves</atitle><jtitle>Journal of pharmacy and pharmacology</jtitle><addtitle>J Pharm Pharmacol</addtitle><date>2000-04</date><risdate>2000</risdate><volume>52</volume><issue>4</issue><spage>451</spage><epage>459</epage><pages>451-459</pages><issn>0022-3573</issn><eissn>2042-7158</eissn><coden>JPPMAB</coden><abstract>The effects of Ginkgo biloba leaf extract on rat brain or livermonoamine oxidase (MAO)‐A and ‐B activity, biogenic amine concentration in nervous tissue, N‐methyl‐d‐aspartate (NMDA)‐ and N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine (DSP‐4)‐induced neurotoxicity and antioxidant activity was investigated to determine the effects of the extract on monoamine catabolism and neuroprotection.
Ginkgo biloba leaf extract was shown to produce in‐vitro inhibition of rat brain MAO‐A and ‐B. The Ginkgo biloba extract was chromatographed on a reverse‐phase HPLC system and two of the components isolated were shown to be MAO inhibitors (MAOIs). These MAOIs were identified by high‐resolution mass spectrometry as kaempferol and isorhamnetin. Pure kaempferol and a number of related flavonoids were examined as MAOIs in‐vitro. Kaempferol, apigenin and chrysin proved to be potent MAOIs, but produced more pronounced inhibition of MAO‐A than MAO‐B. IC50 (50% inhibition concentration) values for the ability of these three flavones to inhibit MAO‐A were 7 times 10−7, 1 times 10−6 and 2 times 10−6 m, respectively. Ginkgo biloba leaf extract and kaempferol were found to have no effect ex‐vivo on rat or mouse brain MAO or on concentrations of dopamine, noradrenaline, 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid. Kaempferol was shown to protect against NMDA‐induced neuronal toxicity in‐vitro in rat cortical cultures, but did not prevent DSP‐4‐induced noradrenergic neurotoxicity in an in‐vivo model. Both Ginkgo biloba extract and kaempferol were demonstrated to be antioxidants in a lipid‐peroxidation assay.
This data indicates that the MAO‐inhibiting activity of Ginkgo biloba extract is primarily due to the presence of kaempferol. Ginkgo biloba extract has properties indicative of potential neuroprotective ability.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>10813558</pmid><doi>10.1211/0022357001774075</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3573 |
| ispartof | Journal of pharmacy and pharmacology, 2000-04, Vol.52 (4), p.451-459 |
| issn | 0022-3573 2042-7158 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_20610223 |
| source | MEDLINE; Access via Wiley Online Library; Oxford University Press Journals All Titles (1996-Current) |
| subjects | 3,4-Dihydroxyphenylacetic Acid - metabolism Administration, Oral Animals Biological and medical sciences Brain - drug effects Brain - enzymology Brain - metabolism Cells, Cultured Chromatography, High Pressure Liquid Dopamine - metabolism Dose-Response Relationship, Drug Flavonoids General pharmacology Ginkgo biloba Ginkgo biloba - chemistry Hydroxyindoleacetic Acid - metabolism Kaempferols Lipid Peroxidation - drug effects Liver - drug effects Liver - enzymology Male Medical sciences Mice Monoamine Oxidase - drug effects Monoamine Oxidase - metabolism Monoamine Oxidase Inhibitors - analysis Monoamine Oxidase Inhibitors - pharmacology N-Methylaspartate - pharmacology Neurons - cytology Neurons - drug effects Neuropharmacology Neuroprotective agent Neuroprotective Agents - pharmacology Norepinephrine - metabolism Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments Plant Extracts - chemistry Plant Extracts - pharmacology Plant Leaves - chemistry Plants, Medicinal Quercetin - analogs & derivatives Quercetin - analysis Quercetin - pharmacology Rats Rats, Sprague-Dawley Serotonin - metabolism Tumor Cells, Cultured - drug effects Tumor Cells, Cultured - metabolism |
| title | Identification of Kaempferol as a Monoamine Oxidase Inhibitor and Potential Neuroprotectant in Extracts of Ginkgo Biloba Leaves |
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