Crocin, a carotenoid pigment, promotes non-rapid eye movement sleep

• Project/Area Number: 25670047
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: University of Tsukuba
• Principal Investigator: ARITAKE Kosuke 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (70390804)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: ノンレム睡眠 / カロテノイド色素 / ヒスタミンH1受容体 / サイクロデキストリングルカノトランスフェラーゼ / クロシン / サフラン / ヒスタミン / カロテノイド

Outline of Final Research Achievements

We compared the effects of crocin in wild-type mice, mice lacking of histamine H1 receptor (H1R) gene, dopamine D2 receptor (D2R) gene or adenosine A1 receptor (A1R) gene by monitoring the locomotor activities and electro encephalogram. In wild-type mice, D2R KO and A1R KO, crocin significantly decreased the locomotor activities and increased the time spent in non-REM sleep. In H1R KO mice, effects of crocin on locomotor activities and non-REM sleep were suppressed. Crocin did not show any specific binding affinities against H1R nor inhibited the histamine release. These results strongly suggested that crocin indirectly suppressed histamine arousal system to induce sleep.
We found enzymatically synthesized crocin-glycoside shows better property in chemical stabilities and photo stabilities than crocin.

Research Products

• [Journal Article] Prostaglandin D2 is crucial for seizure suppression and postictal sleep (2014)
  • Author(s): Kaushik MK, Aritake K, Kamauchi S, Hayaishi O, Huang ZL, Lazarus M, Urade Y
  • Journal Title: Experimental Neurology Volume: 253 Pages: 82-90
  • DOI: 10.1016/j.expneurol.2013.12.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Practical evaluation of liquid chromatography/tandem mass spectrometry and enzyme immunoassay method for the accurate quantitative analysis of prostaglandins. (2014)
  • Author(s): Izumi Y, Aritake K, Urade Y, Fukusaki E.
  • Journal Title: J. Biosci. Bioeng. Volume: 118(1) Issue: 1 Pages: 116-118
  • DOI: 10.1016/j.jbiosc.2013.12.022
  • NAID: 110009838781
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Opposing immunomodulatory roles of prostaglandin D2 during theprogression of skin inflammation. (2014)
  • Author(s): Hana Sarashina, Yoshiki Tsubosaka, Keisuke Omori, Kosuke Aritake, Takayuki Nakagawa, Masatoshi Hori, Hiroyuki Hirai, Masataka Nakamura, Shuh Narumiya, Yoshihiro Urade, Hiroshi Ozaki and Takahisa Murata
  • Journal Title: The Journal of Immunology Volume: 192(1) Issue: 1 Pages: 459-65
  • DOI: 10.4049/jimmunol.1302080
  • Peer Reviewed / Open Access
• [Journal Article] 4. New insights into the catalytic mechanism of Bombyx mori prostaglandin E synthase gained from structure-function analysis. (2013)
  • Author(s): Yamamoto K, Suzuki M, Higashiura A, Aritake K, Urade Y, Uodome N, Hossain T, Nakagawa A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 440 Issue: 4 Pages: 762-767
  • DOI: 10.1016/j.bbrc.2013.10.001
  • Peer Reviewed
• [Journal Article] Elevated CSF histamine levels in multiple sclerosis patients. (2013)
  • Author(s): Kallweit U, Aritake K, Bassetti CL, Blumenthal S, Hayaishi O, Linnebank M, Baumann CR, Urade Y.
  • Journal Title: Fluids Barriers CNS. Volume: 10 Pages: 19-19
• [Journal Article] Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. (2013)
  • Author(s): Taketomi Y, Ueno N, Kojima T, Sato H, Murase R, Yamamoto K, Tanaka S, Sakanaka M, Nakamura M, Nishito Y, Kawana M, Kambe N, Ikeda K, Taguchi R, Nakamizo S, Kabashima K, Gelb MH, Arita M, Yokomizo T, Nakamura M, Watanabe K, Hirai H, Nakamura M, Okayama Y, Ra C, Aritake K et al
  • Journal Title: Nat Immunol. Volume: 14 Issue: 1 Pages: 554-563
  • DOI: 10.1186/1465-9921-14-28
  • Peer Reviewed
• [Presentation] Crocin, a carotenoid pigment of saffron, promotes non-rapid eye movement sleep. (2015)
  • Author(s): Kosuke ARITAKE, Nanako ITO, Yukihiro SHOYAMA、Yoshihiro URADE
  • Organizer: 6th World Congress on Sleep Medicine
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2015-03-25
• [Presentation] サフラン成分のクロシンによるnon-REM睡眠の増強
  • Author(s): 有竹浩介、黄志力、正山征洋、裏出良博
  • Organizer: 第38回日本睡眠学会
  • Place of Presentation: 秋田
• [Presentation] 1. Crocin, a carotenoid pigment, promotes non-rapid eye movement sleep
  • Author(s): Kosuke Aritake, Mika Masaki, Yukihiro Shoyama, Yoshihiro Urade
  • Organizer: Federation of European Biochemical Societies (FEBS) Congress 2013
  • Place of Presentation: St. Petersburg, Russia
• [Book] Food and Brain Health, 2014, Chapter 14 (2014)
  • Author(s): Nguyen Huu Tung, Shinji Soeda, Hiroshi Saito, Kosuke Aritake and Yukihiro Shoyama
  • Total Pages: 339
  • Publisher: Nova Science Pub Inc.
• [Remarks] 筑波大学 国際統合睡眠医科学研究機構 裏出研究室
  • URL: http://urade.wpi-iiis.tsukuba.ac.jp/ja/