Chiu Po Yee, Leung Hoi Yan, Poon Michel K T, Mak Duncan H F, Ko Kam Ming
Department of Biochemistry, Hong Kong University of Science and Technology, SAR, China.
Pharmacology. 2006;77(2):63-70. doi: 10.1159/000092773. Epub 2006 Apr 21.
Effects of schisandrin B enantiomer ((+)Sch B and (-)Sch B) treatment on the reduced cellular glutathione (GSH) level and susceptibility to menadione-induced toxicity were investigated and compared in AML12 hepatocytes. (+)Sch B or (-)Sch B treatment at 6.25 micromol/l produced a time-dependent change in cellular GSH level, with the maximal stimulation occurring 16 h after dosing. (+)Sch B/(-)Sch B pretreatment for 16 h dose-dependently protected against menadione toxicity, with the maximum degree of protection observable at 6.25 micromol/l and the extent of protection afforded by (-)Sch B being larger than that of (+)Sch B. The cytoprotection was associated with a parallel enhancement in cellular GSH level in both non-menadione (control) and menadione-intoxicated cells. While the GSH depletion produced by buthionine sulfoximine/phorone treatment largely abrogated the cytoprotective action of (+)Sch B/(-)Sch B, it almost completely abolished the GSH-enhancing effect of (+)Sch B and (-)Sch B in both control and menadione-treated cells. Both (+)Sch B and (-)Sch B treatments increased the GSH reductase activity in control and menadione-treated cells, with the stimulatory action of (-)Sch B being more potent than that of (+)Sch B in the control condition. (+)Sch B and (-)Sch B also enhanced the gamma-glutamate cysteine ligase activity in menadione-intoxicated cells. The results indicate that (-)Sch B is more effective than (+)Sch B in enhancing cellular GSH and protecting against oxidant injury in hepatocytes.
在AML12肝细胞中研究并比较了五味子醇甲对映体（(+)五味子醇甲和(-)五味子醇甲）处理对细胞内谷胱甘肽（GSH）水平降低及对甲萘醌诱导毒性的易感性的影响。6.25微摩尔/升的(+)五味子醇甲或(-)五味子醇甲处理使细胞内GSH水平产生时间依赖性变化，给药后16小时出现最大刺激作用。(+)五味子醇甲/(-)五味子醇甲预处理16小时剂量依赖性地保护细胞免受甲萘醌毒性，在6.25微摩尔/升时可观察到最大保护程度，且(-)五味子醇甲提供的保护程度大于(+)五味子醇甲。这种细胞保护作用与非甲萘醌（对照）和甲萘醌中毒细胞中细胞内GSH水平的平行升高有关。虽然丁硫氨酸亚砜胺/佛波醇处理导致的GSH耗竭在很大程度上消除了(+)五味子醇甲/(-)五味子醇甲的细胞保护作用，但它几乎完全消除了(+)五味子醇甲和(-)五味子醇甲在对照和甲萘醌处理细胞中的GSH增强作用。(+)五味子醇甲和(-)五味子醇甲处理均增加了对照和甲萘醌处理细胞中的GSH还原酶活性，在对照条件下，(-)五味子醇甲的刺激作用比(+)五味子醇甲更强。(+)五味子醇甲和(-)五味子醇甲还增强了甲萘醌中毒细胞中的γ-谷氨酰半胱氨酸连接酶活性。结果表明，在增强肝细胞内GSH和保护细胞免受氧化损伤方面，(-)五味子醇甲比(+)五味子醇甲更有效。
