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 antidepressive activity. We now report that hyperforin also has N-methyl-D-aspartate (NMDA)-antagonistic effects. Hyperforin (10 microM) 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 microM, 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.
Kumar
Vikas
V
Department of Pharmaceutical Sciences and Collaborative Stroke Center, Texas Tech School of Pharmacy, USA.
Mdzinarishvili
Alexander
A
Kiewert
Cornelia
C
Abbruscato
Thomas
T
Bickel
Ulrich
U
van der Schyf
Cornelis J
CJ
Klein
Jochen
J
D000818:Animals; D001929:Brain Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000473:pathology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020902:Hypericum / Q000737:chemistry*; D066298:In Vitro Techniques; D008297:Male; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013729:Terpenes / Q000494:pharmacology*; D014869:Water Intoxication / Q000188:drug therapy / Q000503:physiopathology
D001643:Bridged Bicyclo Compounds; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D013729:Terpenes; D010696:Phloroglucinol; D002794:Choline; C001654:hyperforin; D002118:Calcium