| In vitro: |
| Acta Pharmacol Sin. 2000 Jan;21(1):75-9. | | Protective effects of bilobalide on amyloid beta-peptide 25-35-induced PC12 cell cytotoxicity.[Pubmed: 11263252] | To study the effect of bilobalide[(-)-Bilobalide], a terpene extracted from the leaves of Ginkgo biloba, on beta-amyloid peptide fragment 25-35 (A beta 25-35)-induced PC12 cell cytotoxicity.
METHODS AND RESULTS:
3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay were used to measure the viability of PC12 cells. Thiobarbituric acid-reactive substances were measured to determine lipid peroxidation of cells. Antioxidant enzymes in PC12 cells were detected. Treatment of PC12 cells with A beta 25-35 (100 mumol.L-1) for 24 h caused a great decrease in cell viability (P < 0.01 compared with control). Bilobalide[(-)-Bilobalide] 25-100 mumol.L-1 dose-dependently attenuated the cytotoxic effect of A beta 25-35. Bilobalide[(-)-Bilobalide] also inhibited A beta 25-35 (100 mumol.L-1)-induced elevation of lipid peroxidation and decline of antioxidant enzyme activities.
CONCLUSIONS:
Bilobalide[(-)-Bilobalide] protected PC12 cells from A beta 25-35-induced cytotoxicity. | | Apoptosis . 2010 Jun;15(6):715-27. | | Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells[Pubmed: 20333467] | | Abstract
Bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, has been proposed to exert protective and trophic effects on neurons. However, mechanisms underlying the protective effects of bilobalide remain unclear. Using human SH-SY5Y neuroblastoma cells and primary hippocampal neurons, this study investigated the neuroprotective effects of bilobalide. We mimicked aging-associated neuronal impairments by applying external factors (beta amyloid protein (Abeta) 1-42, H(2)O(2) and serum deprivation) consequently inducing cell apoptosis. As markers for apoptosis, cell viability, DNA fragmentation, mitochondrial membrane potential and levels of cleaved caspase 3 were measured. We found that, bilobalide prevented Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptosis. To better understand the neuroprotective effects of bilobalide, we also tested the ability of bilobalide to modulate pro-survival signaling pathways such as protein kinase C (PKC), extracellular-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. It was found that, bilobalide dose-dependently increased PI3K activity and levels of phosphorylated Akt (p-Akt Ser473 and Thr308), which could be maintained up to at least 2 h after bilobalide withdrawal in cells treated with or without Abeta 1-42, H(2)O(2) or serum-free medium. In addition, application of PI3K/Akt inhibitor LY294002 could abrogate both the protective effects of bilobalide against Abeta 1-42-, H(2)O(2)- and serum deprivation-induced apoptotic cell damage and bilobalide-induced increase in PI3K activity and levels of p-Akt (Ser473 and Thr308). In contrast, application of PKC inhibitor staurosporine (STS) did not affect the protective effects of bilobalide. Moreover, no change in levels of phosphorylated ERK1/2 (p-ERK1/2) was observed in bilobalide-treated cells. These results further suggested that the PI3K/Akt pathway might be involved in the protective effects of bilobalide. Since modern technology allows production of purified bilobalide with high bioavailability, bilobalide may be useful in developing therapy for diseases involving age-associated neurodegeneration. |
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| In vivo: |
| Eur J Pharmacol. 1999 Feb 19;367(2-3):165-73. | | Effects of bilobalide on gamma-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain.[Pubmed: 10078989] | We have previously demonstrated that Bilobalide[(-)-Bilobalide] a constituent of the Ginkgo biloba extract, possesses anticonvulsant activity, and suggested that the mechanism of its anticonvulsant action involves modulation of y-aminobutyric acid (GABA)-related neuronal transmission.
METHODS AND RESULTS:
This study examined the effects of Bilobalide[(-)-Bilobalide] on the level of GABA and glutamate, the activity and the amount of glutamic acid decarboxylase (EC 4.1.1.15), and the function of GABA(A) receptors in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels, glutamic acid decarboxylase activity, and the protein amount of 67 kDa glutamic acid decarboxylase in the hippocampus of mice treated withBilobalide[(-)-Bilobalide] (30 mg/kg, p.o., once a day for 4 days) were significantly higher than those in controls. However, there were no significant differences in glutamate levels or, the number and the dissociation constants of GABA(A) receptors in the hippocampus between control and bilobalide-treated mice.
CONCLUSIONS:
These results suggest that the anticonvulsant effect of bilobalide is due to elevation of GABA levels, possibly through potentiation of glutamic acid decarboxylase activity and enhancement of the protein amount of 67 kDa glutamic acid decarboxylase by bilobalideBilobalide[(-)-Bilobalide]. |
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