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Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells.
Apoptosis. 2010 Jun; 15(6):715-27.A

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.

Authors+Show Affiliations

Department of Anatomy, Sun Yat-Sen University Guangzhou, Guangdong, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20333467

Citation

Shi, Chun, et al. "Bilobalide Prevents Apoptosis Through Activation of the PI3K/Akt Pathway in SH-SY5Y Cells." Apoptosis : an International Journal On Programmed Cell Death, vol. 15, no. 6, 2010, pp. 715-27.
Shi C, Wu F, Yew DT, et al. Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells. Apoptosis. 2010;15(6):715-27.
Shi, C., Wu, F., Yew, D. T., Xu, J., & Zhu, Y. (2010). Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells. Apoptosis : an International Journal On Programmed Cell Death, 15(6), 715-27. https://doi.org/10.1007/s10495-010-0492-x
Shi C, et al. Bilobalide Prevents Apoptosis Through Activation of the PI3K/Akt Pathway in SH-SY5Y Cells. Apoptosis. 2010;15(6):715-27. PubMed PMID: 20333467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bilobalide prevents apoptosis through activation of the PI3K/Akt pathway in SH-SY5Y cells. AU - Shi,Chun, AU - Wu,Fengming, AU - Yew,David T, AU - Xu,Jie, AU - Zhu,Yonghong, PY - 2010/3/25/entrez PY - 2010/3/25/pubmed PY - 2010/9/15/medline SP - 715 EP - 27 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 15 IS - 6 N2 - 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. SN - 1573-675X UR - https://www.unboundmedicine.com/medline/citation/20333467/Bilobalide_prevents_apoptosis_through_activation_of_the_PI3K/Akt_pathway_in_SH_SY5Y_cells_ L2 - https://doi.org/10.1007/s10495-010-0492-x DB - PRIME DP - Unbound Medicine ER -