NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort
Extracts of the medicinal plant St. John’s wort (Hypericum perforatum) are widely used for the treatment of affective disorders. Hyperforin, a constituent of St. John’s wort, is known to modulate the release and re-uptake of various neurotransmitters, an action that likely underlies its antidepressi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319344159 |
| _version_ | 1818476873511862272 |
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| author | Vikas Kumar Alexander Mdzinarishvili Cornelia Kiewert Thomas Abbruscato Ulrich Bickel Cornelis J. van der Schyf Jochen Klein |
| author_facet | Vikas Kumar Alexander Mdzinarishvili Cornelia Kiewert Thomas Abbruscato Ulrich Bickel Cornelis J. van der Schyf Jochen Klein |
| author_sort | Vikas Kumar |
| collection | DOAJ |
| description | Extracts of the medicinal plant St. John’s wort (Hypericum perforatum) are widely used for the treatment of affective disorders. Hyperforin, a constituent of St. John’s wort, is known to modulate the release and re-uptake of various neurotransmitters, an action that likely underlies its antidepressive activity. We now report that hyperforin also has N-methyl-D-aspartate (NMDA)-antagonistic effects. Hyperforin (10 µM) was found to inhibit the NMDA-induced calcium influx into cortical neurons. In rat hippocampal slices, hyperforin inhibited the NMDA-receptor-mediated release of choline from phospholipids. Hyperforin also antagonized the increase of water content in freshly isolated hippocampal slices, and it counteracted, at 3 and 10 µM, the increase of water content induced by NMDA. Hyperforin was inactive, however, in two in vivo models of brain edema formation, middle cerebral artery occlusion and water intoxication in mice. In conclusion, hyperforin has NMDA-receptor-antagonistic and potential neuroprotective effects in vitro. This effect may contribute to the therapeutic effectiveness of St. John’s wort extracts in some situations, for example, for relapse prevention in alcoholism. Keywords:: edema, fura-2, hippocampal slice, middle cerebral artery occlusion, water intoxication |
| first_indexed | 2024-12-10T09:30:54Z |
| format | Article |
| id | doaj.art-185edc9e339849b095d5877053c8dd53 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T09:30:54Z |
| publishDate | 2006-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-185edc9e339849b095d5877053c8dd532022-12-22T01:54:21ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-0110214754NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s WortVikas Kumar0Alexander Mdzinarishvili1Cornelia Kiewert2Thomas Abbruscato3Ulrich Bickel4Cornelis J. van der Schyf5Jochen Klein6Department of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USADepartment of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USADepartment of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USADepartment of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USADepartment of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USADepartment of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USADepartment of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, Amarillo, Texas 79106, USA; Corresponding author. jochen.klein@ttuhsc.eduExtracts of the medicinal plant St. John’s wort (Hypericum perforatum) are widely used for the treatment of affective disorders. Hyperforin, a constituent of St. John’s wort, is known to modulate the release and re-uptake of various neurotransmitters, an action that likely underlies its antidepressive activity. We now report that hyperforin also has N-methyl-D-aspartate (NMDA)-antagonistic effects. Hyperforin (10 µM) was found to inhibit the NMDA-induced calcium influx into cortical neurons. In rat hippocampal slices, hyperforin inhibited the NMDA-receptor-mediated release of choline from phospholipids. Hyperforin also antagonized the increase of water content in freshly isolated hippocampal slices, and it counteracted, at 3 and 10 µM, the increase of water content induced by NMDA. Hyperforin was inactive, however, in two in vivo models of brain edema formation, middle cerebral artery occlusion and water intoxication in mice. In conclusion, hyperforin has NMDA-receptor-antagonistic and potential neuroprotective effects in vitro. This effect may contribute to the therapeutic effectiveness of St. John’s wort extracts in some situations, for example, for relapse prevention in alcoholism. Keywords:: edema, fura-2, hippocampal slice, middle cerebral artery occlusion, water intoxicationhttp://www.sciencedirect.com/science/article/pii/S1347861319344159 |
| spellingShingle | Vikas Kumar Alexander Mdzinarishvili Cornelia Kiewert Thomas Abbruscato Ulrich Bickel Cornelis J. van der Schyf Jochen Klein NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort Journal of Pharmacological Sciences |
| title | NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort |
| title_full | NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort |
| title_fullStr | NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort |
| title_full_unstemmed | NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort |
| title_short | NMDA Receptor-Antagonistic Properties of Hyperforin, a Constituent of St. John’s Wort |
| title_sort | nmda receptor antagonistic properties of hyperforin a constituent of st john s wort |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319344159 |
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