Skip to main content

Advertisement

Log in

Effects of saffron and its constituents, crocin-1, crocin-2, and crocetin on α-synuclein fibrils

  • Original Paper
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Saffron, the stigma of Crocus sativus Linné (Iridaceae family), has been known to inhibit aggregation of β-amyloid, a nerve tissue protein. α-Synuclein (αS) is a 140-amino acid protein found abundantly in various regions of the brain. Its abnormal aggregation and accumulation in nerve tissue are said to cause neurodegenerative diseases such as Parkinson’s disease, Lewy body dementia, and multiple-system atrophy. This study (part of this study was presented at the 137th Annual Meeting of the Pharmaceutical Society of Japan) examined the effects of saffron, its constituents (crocin-1, crocin-2, crocetin, and safranal), and crocetin structural analogs (hexadecanedioic acid, norbixin, and trans, trans-muconic acid) on αS aggregation, and αS fibril dissociation. Saffron dose-dependently inhibited αS aggregation and dissociated αS fibrils by thioflavin T fluorescence assay. These effects were observed by transmission electron microscopy, which showed reduced and shortened αS fibrils. Crocin-1, crocin-2, and crocetin showed anti-aggregation and fibril dissociation effects, with crocetin being the most potent. The effects of norbixin were weaker than those of crocetin, and the other crocetin structural analogs showed no effects. These results show that saffron and its constituents (crocin-1, crocin-2, and crocetin) can be effective in preventing and treating diseases caused by abnormal αS aggregation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Burré J (2015) The synaptic function of α-synuclein. J Parkinsons Dis 5:699–713

    Article  PubMed  PubMed Central  Google Scholar 

  2. Goedert M (2001) Alpha-synuclein and neurodegenerative diseases. Nat Rev Neurosci 2:492–501

    Article  CAS  PubMed  Google Scholar 

  3. Hamilton RL (2000) Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 10:378–384

    Article  CAS  PubMed  Google Scholar 

  4. Tsigelny IF, Crews L, Desplats P, Shaked GM, Sharikov Y, Mizuno H, Spencer B, Rockenstein E, Trejo M, Platoshyn O, Yuan JX, Masliah E (2008) Mechanisms of hybrid oligomer formation in the pathogenesis of combined Alzheimer’s and Parkinson’s Diseases. PLoS ONE 3:e3135

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ji K, Zhao Y, Yu T, Wang Z, Gong H, Yang X, Liu Y, Huang K (2016) Inhibition effects of tanshinone on the aggregation of α-synuclein. Food Funct 7:409–416

    Article  CAS  PubMed  Google Scholar 

  6. Ardah MT, Paleologou KE, Lv G, Menon SA, Abul Khair SB, Lu JH, Safieh-Garabedian B, Al-Hayani AA, Eliezer D, Li M, El-Agnaf OM (2015) Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils. Neurobiol Dis 74:89–101

    Article  CAS  PubMed  Google Scholar 

  7. Ardah MT, Paleologou KE, Lv G, Abul Khair SB, Kazim AS, Minhas ST, Al-Tel TH, Al-Hayani AA, Haque ME, Eliezer D, El-Agnaf OM (2014) Structure activity relationship of phenolic acid inhibitors of α-synuclein fibril formation and toxicity. Front Aging Neurosci 6:197

    Article  PubMed  PubMed Central  Google Scholar 

  8. Namba T (1980) Colored illustrations of Wakan-Yaku Vol. II, Hoikusha, Osaka. pp 114–117

  9. Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M, Lamari FN (2006) Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 54:8762–8768

    Article  CAS  PubMed  Google Scholar 

  10. Ahn JH, Hu Y, Hernandez M, Kim JR (2011) Crocetin inhibits beta-amyloid fibrillization and stabilizes beta-amyloid oligomers. Biochem Biophys Res Commun 414:79–83

    Article  CAS  PubMed  Google Scholar 

  11. Ghahghaei A, Bathaie SZ, Kheirkhah H, Bahraminejad E (2013) The protective effect of crocin on the amyloid fibril formation of Aβ42 peptide in vitro. Cell Mol Biol Lett 18:328–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Karakani AM, Riazi G, Mahmood Ghaffari S, Ahmadian S, Mokhtari F, Jalili Firuzi M, Zahra Bathaie S (2015) Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro. Iran J Basic Med Sci 18:485–492

    PubMed  PubMed Central  Google Scholar 

  13. Tong Y, Yan Y, Zhu X, Liu R, Gong F, Zhang L, Wang P (2015) Simultaneous quantification of crocetin esters and picrocrocin changes in Chinese saffron by high-performance liquid chromatography-diode array detector during 15 years of storage. Pharmacogn Mag 11:540–545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ardah MT, Paleologou KE, Lv G, Menon SA, Abul Khair SB, Lu JH, Safieh-Garabedian B, Al-Hayani AA, Eliezer D, Li M, El-Agnaf OM (2015) Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils. Neurobiol Dis 74:89–101

    Article  CAS  PubMed  Google Scholar 

  15. LeVine H 3rd (1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309:274–284

    Article  CAS  PubMed  Google Scholar 

  16. Ono K, Yamada M (2007) Vitamin A potently destabilizes preformed alpha-synuclein fibrils in vitro: implications for Lewy body diseases. Neurobiol Dis 25:446–454

    Article  CAS  PubMed  Google Scholar 

  17. Asai A, Nakano T, Takahashi M, Nagao A (2005) Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J Agric Food Chem 53:7302–7306

    Article  CAS  PubMed  Google Scholar 

  18. Yoshino F, Yoshida A, Umigai N, Kubo K, Lee MC (2011) Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain. J Clin Biochem Nutr 49:182–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

TEM study was conducted at the University of Tokyo, supported by Nanotechnology Platform Program (Molecule and Material Synthesis) of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eiji Inoue.

Ethics declarations

Conflict of interest

This research was supported by Kyushin Pharmaceutical Co., Ltd. The authors declare that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Inoue, E., Shimizu, Y., Masui, R. et al. Effects of saffron and its constituents, crocin-1, crocin-2, and crocetin on α-synuclein fibrils. J Nat Med 72, 274–279 (2018). https://doi.org/10.1007/s11418-017-1150-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-017-1150-1

Keywords

Navigation