Ahlemeyer B, Möwes A, Krieglstein J
Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie der Philipps-Universität Marburg, Germany.
Eur J Pharmacol. 1999 Feb 19;367(2-3):423-30. doi: 10.1016/s0014-2999(98)00903-0.
Previous studies have already demonstrated that some constituents of an extract of Ginkgo biloba (EGb), such as ginkgolide B and bilobalide, protect cultured neurons from hypoxia- and glutamate-induced damage. This prompted us to investigate whether they were also able to inhibit neuronal apoptosis. We induced apoptosis in cultured chick embryonic neurons as well as in mixed cultures of neurons and astrocytes from neonatal rat hippocampus by serum deprivation and staurosporine. The increase in the percentage of apoptotic chick neurons from 12% in controls to 30% after 24 h of serum deprivation was reduced to control level by EGb (10 mg/l), ginkgolide B (10 microM), ginkgolide J (100 microM) and bilobalide (1 microM). After treatment with staurosporine (200 nM) for 24 h we observed 74% apoptotic chick neurons. This percentage of apoptotic neurons was reduced to 24%, 62% and 31% in the presence of EGb (100 mg/l), ginkgolide J (100 microM) and ginkgolide B (10 microM), respectively. Bilobalide (10 microM) decreased apoptotic damage induced by staurosporine treatment for 12 h nearly to the control level. In mixed neuronal/glial cultures, the extract of EGb (100 mg/l) and bilobalide (100 microM) rescued rat neurons from apoptosis caused by serum deprivation, whereas, bilobalide (100 microM) and ginkgolide B (100 microM) reduced staurosporine-induced apoptotic damage. Ginkgolide A revealed no anti-apoptotic effect in either serum-deprived or staurosporine-treated neurons. Our results suggest that EGb and some of its constituents possess anti-apoptotic capacity and that bilobalide is the most potent constituent.
先前的研究已经证明，银杏叶提取物（EGb）的某些成分，如银杏内酯B和白果内酯，可保护培养的神经元免受缺氧和谷氨酸诱导的损伤。这促使我们研究它们是否也能够抑制神经元凋亡。我们通过血清剥夺和星形孢菌素在培养的鸡胚神经元以及新生大鼠海马神经元和星形胶质细胞的混合培养物中诱导凋亡。血清剥夺24小时后，凋亡鸡神经元的百分比从对照组的12%增加到30%，而EGb（10mg/l）、银杏内酯B（10μM）、银杏内酯J（100μM）和白果内酯（1μM）可将其降低至对照水平。用星形孢菌素（200nM）处理24小时后，我们观察到74%的凋亡鸡神经元。在EGb（100mg/l）、银杏内酯J（100μM）和银杏内酯B（10μM）存在的情况下，凋亡神经元的百分比分别降至24%、62%和31%。白果内酯（10μM）将星形孢菌素处理12小时诱导的凋亡损伤几乎降低至对照水平。在神经元/神经胶质混合培养物中，EGb提取物（100mg/l）和白果内酯（100μM）可使大鼠神经元免受血清剥夺引起的凋亡，而白果内酯（100μM）和银杏内酯B（100μM）可减少星形孢菌素诱导的凋亡损伤。银杏内酯A在血清剥夺或星形孢菌素处理的神经元中均未显示出抗凋亡作用。我们的结果表明，EGb及其某些成分具有抗凋亡能力，且白果内酯是最有效的成分。
