Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo

Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo
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DOI:
10.1016/j.bbagen.2006.11.012
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发表时间:
2007-04-01
影响因子:
3
通讯作者:
Soeda, Shinji
Soeda, Shinji
中科院分区:
生物学3区
文献类型:
--
作者:
Ochiai, Takashi;Shimeno, Hiroshi;Soeda, Shinji

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藏红花(Crocus sativus L.,藏红花)被用作调味料和食品上色的香料,在中国传统医学中用作止痛药或镇定剂。本课前研究发现,藏红花类胡萝卜素藏红花素可通过增加谷胱甘肽(GSH)合成,抑制中性鞘磷脂酶(nSMase)活性和神经酰胺形成,从而抑制血清剥夺诱导的pc12细胞死亡。藏红花的类胡萝卜素色素由藏红花素二-(β -d -葡萄糖基)酯[二红素]、藏红花素-(β -d -龙胆生物基)-(β -d -葡萄糖基)酯[三红素]和藏红花素二-(β -d -龙胆生物基)酯[藏红花素]组成。藏红花还含有微藏红花素,这种物质会导致藏红花的苦味。在本研究中,为了证实藏红花的神经保护作用是否仅由藏红花素引起,我们在无血清和缺氧条件下检测了这些藏红花素在PC12细胞中的抗氧化和gsh合成活性。细胞活力、过氧化膜脂和caspase-3活性的测定表明,在10 μ M浓度下,藏红花素的神经保护效力依次为藏红花素、三头星、三头星、三头星、三头星和微番星(后两种藏红花素的神经保护效力很小或没有)。此外,我们发现在这些藏红花成分中,藏红花素最有效地促进γ -谷氨酰半胱氨酸合成酶(γ - gcs)的mRNA表达,这种酶作为限速酶有助于GSH的合成,类胡萝卜素可以显著减少小鼠大脑中动脉(MCA)闭塞引起的梗死面积。(c) 2006 Elsevier b.v.版权所有
Crocus sativus L. (saffron) has been used as a spice for flavoring and coloring food preparations, and in Chinese traditional medicine as an anodyne or tranquilizer. Our previous study demonstrated that crocin, a carotenoid pigment of saffron, can suppress the serum deprivation -induced death of PC 12 cells by increasing glutathione (GSH) synthesis and thus inhibiting neutral sphingomyelinase (nSMase) activity and ceramide formation. The carotenoid pigments of saffron consist of crocetin di-(beta-D-glucosyl)-ester [dicrocin], crocetin-(beta-D-gentiobiosyl)-( beta-D-glucosyl)ester [tricrocin] and crocetin-di-(beta-D-gentiobiosyl)-ester [crocin]. Saffron also contains picrocrocin, the substance causing saffron's bitter taste. In this study, to confirm whether neuroprotective effects of saffron are caused solely by crocin, we examined the antioxidant and GSH-synthetic activities of these crocins in PC12 cells under serum-free and hypoxic conditions. Measurements of cell viability, peroxidized membrane lipids and caspase-3 activity showed that the rank order of the neuroprotective potency at a concentration of 10 mu M was crocin > tricrocin > dicrocin and picrocrocin (the latter two crocins had a little or no potency). In addition, we show that among these saffron's constituents, crocin most effectively promotes mRNA expression of gamma-glutamylcysteinyl synthase (gamma-GCS), which contributes to GSH synthesis as the rate-limiting enzyme, and that the carotenoid can significantly reduce infarcted areas caused by occlusion of the middle cerebral artery (MCA) in mice. (c) 2006 Elsevier B.V All rights reserved.