TY - JOUR
T1 - Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo
AU - Ochiai, Takashi
AU - Shimeno, Hiroshi
AU - Mishima, Ken ichi
AU - Iwasaki, Katsunori
AU - Fujiwara, Michihiro
AU - Tanaka, Hiroyuki
AU - Shoyama, Yukihiro
AU - Toda, Akihisa
AU - Eyanagi, Reiko
AU - Soeda, Shinji
N1 - Funding Information:
This work was supported in part by funds from the Central Research Institute of Fukuoka University and from MEXT. HAITEKU (2002–2006). Our thanks to Mr. Steven Sabotta for reading the manuscript.
PY - 2007/4
Y1 - 2007/4
N2 - 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 PC12 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-(β-d-glucosyl)-ester [dicrocin], crocetin-(β-d-gentiobiosyl)-(β-d-glucosyl)-ester [tricrocin] and crocetin-di-(β-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 μM 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 γ-glutamylcysteinyl synthase (γ-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.
AB - 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 PC12 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-(β-d-glucosyl)-ester [dicrocin], crocetin-(β-d-gentiobiosyl)-(β-d-glucosyl)-ester [tricrocin] and crocetin-di-(β-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 μM 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 γ-glutamylcysteinyl synthase (γ-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.
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U2 - 10.1016/j.bbagen.2006.11.012
DO - 10.1016/j.bbagen.2006.11.012
M3 - Article
C2 - 17215084
AN - SCOPUS:33847151661
VL - 1770
SP - 578
EP - 584
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
SN - 0304-4165
IS - 4
ER -