Bilobalide and PC12 cells: A structure activity relationship study.

Ginkgo biloba extracts have been postulated to beneficial for improving cognitive function and as such they have been used as a potential treatment of Alzheimer's disease. The main active ingredients of the extract are terpene trilactones (TTLs), such as bilobalide (BB) and ginkgolides. Several structure-activity relationship (SAR) studies using ginkgolide scaffolds produced more biologically potent species by modification of the lactone moieties. However, modifications of BB scaffold have been limited, and no SAR studies on BB have been accomplished to date. Thus, the aim of this study was to elucidate how the modification of the lactone moieties of BB would affect their biological activities in a number of assays, including proliferating cell activity, neuroprotective effects against Aß (1-40) peptides, and neurite outgrowth effects in PC12 neuronal cells. It appeared that the derivatives containing lactone groups showed similar biological activity to native BB, while those that possessed no lactone moieties exhibited lower neurite outgrowth effects. Thus, the results suggested that the lactone moieties of BB played an important role in exerting neurite outgrowth effects in PC12 cells.

Chiral Lewis acid catalyzed asymmetric cycloadditions of carbonyl ylides generated from diazoimide derivatives and their synthetic applications to indolizidine alkaloids.

Highly enantioselective 1,3-dipolar cycloaddition reactions, catalyzed by chiral Lewis acids, between several 3-(2-alkenoyl)-2-oxazolidinones and carbonyl ylides that were generated from N-diazoacetyl lactams are described. Reactions of N-diazoacetyl lactams that possess 5-, 6-, and 7-membered rings were transformed to the corresponding epoxy-bridged indolizidines, quinolizidines, and 1-azabicyclo[5.4.0]undecanes with good to high enantioselectivities. Regio- and stereoselective ring-opening of the epoxy-bridged indolizidine cycloadduct gave the corresponding alcohol as a single diastereomer. The sequence of asymmetric cycloaddition followed by ring-opening was applied to the syntheses of several chiral indolizidine derivatives, including (+)-tashiromine.

The facilitative effects of bilobalide, a unique constituent of Ginkgo biloba, on synaptic transmission and plasticity in hippocampal subfields.

Bilobalide, a unique constituent of Ginkgo biloba, has been reported to potentiate population spikes in hippocampal CA1 pyramidal cells and to protect the brain against cell death. In this study, the effects of bilobalide on synaptic transmission and its plasticity in rat hippocampal subfields were electrophysiologically investigated. Bilobalide (50 µM) significantly potentiated the input-output relationship at Schaffer collateral (SC)-CA1 synapses but not at medial perforant path (MPP)-dentate gyrus (DG), lateral perforant path (LPP)-DG, or mossy fiber (MF)-CA3 synapses. Facilitative effects of bilobalide on synaptic plasticity were only observed at MPP-DG synapses, in which the induction of long-term depression was blocked in the presence of bilobalide. However, no effect on synaptic plasticity was observed at SC-CA1 synapses. These results suggest that bilobalide has differential effects on synaptic efficacy in each hippocampal subfield.