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Pharmacological activities of crocin in saffron

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Abstract

The effect of crocin on improving ethanol-induced impairment of learning behaviors of mice in passive avoidance tasks is reported. Based on these results, it became evident that crocin prevents the inhibitory effect of ethanol on long-term potentiation (LTP) in the dentate gyrus in vivo. We confirmed that crocin inhibits tumor necrosis factor (TNF)-α-induced apoptosis of PC-12 cells. PC-12 cells showed a rapid increase in cellular ceramide levels, followed by an increase in the phosphorylation of c-Jun kinase (JNK), leading to apoptosis by serum/glucose deprivation in the medium. The production of ceramide was dependent on the activation of magnesium-dependent neutral sphingomyelinase (N-SMase), but not on de novo synthesis. The oxidative stress also decreased the cellular levels of glutathione (GSH), which is the potent inhibitor of N-SMase. Crocin treatment resulted in the prevention of N-SMase activation, ceramide production and JNK phosphorylation. Exploration of the crocin’s preventive mechanism in oxidative stress-induced cell death revealed that the activities of GSH reductase and γ-glutamylcysteinyl synthase (γ-GCS) in the γ-glutamyl cycle affected the stable GSH supply that blocks the activation of N-SMase. These results strongly support the importance of the proposed GSH-dependent inhibitory mechanism in oxidative stress-mediated cell death.

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Abbreviations

A-Smase:

Acidic Smase

BSO:

Buthionine sulfoximine

DMEM:

Dulbecco’s modified Eagle’s medium

ELISA:

Enzyme-linked immunosorbent assay

FB1:

Fumonisin B1

γ-GCS:

γ-Glutamylcysteinyl synthase

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Glutathione

IL-6:

Interleukin-6

JNK:

c-Jun kinase

LTP:

Long-term potentiation

Mab:

Monoclonal antibody

NGF:

Nerve growth factor

NMDA:

N-methyl-d-aspartate

N-Smase:

Neutral sphingomyelinase

PS:

Phosphatidylserine

SAPK:

Stress-activated protein kinase

SD:

Step down

SM:

Sphingomyelin

SOD:

Superoxide dismutase

ST:

Step through

TNF-α:

Tumor necrosis factor

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Acknowledgements

This review has been prepared as part of the Asian Core Program supported by Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan

    Shinji Soeda, Takashi Ochiai & Hiroshi Shimeno

  2. Faculty of Pharmacy, Musashino University, Nishi-tokyoshi, Tokyo, 202-8585, Japan

    Hiroshi Saito & Kazuho Abe

  3. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Hiroyuki Tanaka & Yukihiro Shoyama

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  1. Shinji Soeda
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  2. Takashi Ochiai
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  5. Kazuho Abe
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Correspondence to Yukihiro Shoyama.

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Soeda, S., Ochiai, T., Shimeno, H. et al. Pharmacological activities of crocin in saffron. J Nat Med 61, 102–111 (2007). https://doi.org/10.1007/s11418-006-0120-9

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