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.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Alzheimer Disease/drug therapy , Amyloid/metabolism , Hypericum/metabolism , Phloroglucinol/analogs & derivatives , Plant Extracts/pharmacology , Terpenes/pharmacology , Animals , Brain/metabolism , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Phloroglucinol/pharmacologyABSTRACT
Transmissible spongiform encephalopathies (TSE) are characterized by the misfolding of the host encoded prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)) which leads to the accumulation of ß-sheet-rich fibrils and subsequent loss of neurons and synaptic functions. Although many compounds have been identified which inhibit accumulation or dissolve fibrils and aggregates in vitro there is no therapeutic treatment to stop these progressive neurodegenerative diseases. Here we describe the effects of the traditional medicinal herb Scutellaria lateriflora (S. lateriflora) and its natural compounds, the flavonoids baicalein and baicalin, on the development of prion disease using in vitro and in vivo models. S. lateriflora extract as well as both constituents reduced the PrP(res) accumulation in scrapie-infected cell cultures and cell-free conversion assays and lead to the destabilization of pre-existing PrP(Sc) fibrils. Moreover, tea prepared from S. lateriflora, prolonged significantly the incubation time of scrapie-infected mice upon oral treatment. Therefore S. lateriflora extracts as well as the individual compounds can be considered as promising candidates for the development of new therapeutic drugs against TSEs and other neurodegenerative diseases like Alzheimer's and Parkinson's disease.
