Journal of Natural Medicines

, Volume 61, Issue 2, pp 102–111

Pharmacological activities of crocin in saffron

  • Shinji Soeda
  • Takashi Ochiai
  • Hiroshi Shimeno
  • Hiroshi Saito
  • Kazuho Abe
  • Hiroyuki Tanaka
  • Yukihiro Shoyama
Review

DOI: 10.1007/s11418-006-0120-9

Cite this article as:
Soeda, S., Ochiai, T., Shimeno, H. et al. J Nat Med (2007) 61: 102. doi:10.1007/s11418-006-0120-9

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.

Keywords

Antioxidant effectCrocinCrocus sativus L.Neuronal apoptosisNeuroprotective effect

Abbreviation

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

Copyright information

© The Japanese Society of Pharmacognosy and Springer 2007

Authors and Affiliations

  • Shinji Soeda
    • 1
  • Takashi Ochiai
    • 1
  • Hiroshi Shimeno
    • 1
  • Hiroshi Saito
    • 2
  • Kazuho Abe
    • 2
  • Hiroyuki Tanaka
    • 3
  • Yukihiro Shoyama
    • 3
  1. 1.Department of Biochemistry, Faculty of Pharmaceutical SciencesFukuoka UniversityFukuokaJapan
  2. 2.Faculty of PharmacyMusashino UniversityNishi-tokyoshi, TokyoJapan
  3. 3.Department of Pharmacognosy, Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan