title: St. John's Wort reduces beta-amyloid accumulation in a double transgenic Alzheimer's disease mouse model-role of P-glycoprotein.
abstract: The adenosine triphosphate-binding cassette transport protein P-glycoprotein (ABCB1) is involved in the export of beta-amyloid from the brain into the blood, and there is evidence that age-associated deficits in cerebral P-glycoprotein content may be involved in Alzheimer's disease pathogenesis. P-glycoprotein function and expression can be pharmacologically induced by a variety of compounds including extracts of Hypericum perforatum (St. John's Wort). To clarify the effect of St. John's Wort on the accumulation of beta-amyloid and P-glycoprotein expression in the brain, St. John's Wort extract (final hyperforin concentration 5%) was fed to 30-day-old male C57BL/6J-APP/PS1(+/-) mice over a period of 60 or 120 days, respectively. Age-matched male C57BL/6J-APP/PS1(+/-) mice receiving a St. John's Wort-free diet served as controls. Mice receiving St. John's Wort extract showed (i) significant reductions of parenchymal beta-amyloid 1-40 and 1-42 accumulation; and (ii) moderate, but statistically significant increases in cerebrovascular P-glycoprotein expression. Thus, the induction of cerebrovascular P-glycoprotein may be a novel therapeutic strategy to protect the brain from beta-amyloid accumulation, and thereby impede the progression of Alzheimer's disease.
authors.affiliation: Department of Neuropathology, Institute of Pathology, University of Greifswald, Greifswald, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Brenn
authors.forename: Markus
authors.initials: M
authors.lastname: Grube
authors.forename: Gabriele
authors.initials: G
authors.lastname: Jedlitschky
authors.forename: Andrea
authors.initials: A
authors.lastname: Fischer
authors.forename: Barbara
authors.initials: B
authors.lastname: Strohmeier
authors.forename: Martin
authors.initials: M
authors.lastname: Eiden
authors.forename: Markus
authors.initials: M
authors.lastname: Keller
authors.forename: Martin H
authors.initials: MH
authors.lastname: Groschup
authors.forename: Silke
authors.initials: S
authors.lastname: Vogelgesang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D020902:Hypericum / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000682:Amyloid; D010936:Plant Extracts; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin
keywords: Alzheimer's disease; P-glycoprotein; St. John's Wort; beta-amyloid; blood-brain barrier