Planta Medica International Open 2016; 3(03): e60-e62
DOI: 10.1055/s-0042-118778
Letter
Georg Thieme Verlag KG Stuttgart · New York

Limonene Enhances the cAMP Response Element (CRE)-Dependent Transcriptional Activity Activated via Adenosine A2 A Receptor in a Neural-Crest Derived Cell Line, PC-12

Jiro Takito*
1   Department of Anti-Dementia Functional Food Development, Graduate School of Engineering, Tohoku University, Aoba, Aramaki, Sendai, Japan
2   Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo, Japan
,
Masaki Ota
3   Research Center of Supercritical Fluid Technology, Tohoku University, Aoba-ku, Aramaki, Sendai, Japan
,
Chisato Oba
3   Research Center of Supercritical Fluid Technology, Tohoku University, Aoba-ku, Aramaki, Sendai, Japan
,
Hironori Fujiwara
1   Department of Anti-Dementia Functional Food Development, Graduate School of Engineering, Tohoku University, Aoba, Aramaki, Sendai, Japan
,
Kiyoshi Murata
4   Japan Royal Jelly (JRJ) Co. Ltd., R&D Center, Ganbara, Kami-machi, Kami-gun, Miyagi, Japan
,
Kikuji Yamaguchi*
1   Department of Anti-Dementia Functional Food Development, Graduate School of Engineering, Tohoku University, Aoba, Aramaki, Sendai, Japan
5   Japan Royal Jelly (JRJ) Co. Ltd., Kyobashi, Chuo-ku, Tokyo, Japan
,
Nobuyuki Uozumi
6   Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Aoba, Aramaki, Sendai, Japan
,
Masanori Nakamura
2   Department of Oral Anatomy and Developmental Biology, School of Dentistry, Showa University, Hatanodai, Shinagawa, Tokyo, Japan
,
Hiroshi Inomata
3   Research Center of Supercritical Fluid Technology, Tohoku University, Aoba-ku, Aramaki, Sendai, Japan
,
Yasushi Ohizumi*
1   Department of Anti-Dementia Functional Food Development, Graduate School of Engineering, Tohoku University, Aoba, Aramaki, Sendai, Japan
7   Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan
8   Kansei Fukushi Research Center, Tohoku Fukushi University, Kunimi, Aoba-ku, Sendai, Japan
› Author Affiliations
Further Information

Publication History

received 10 February 2016
revised 30 July 2016

accepted 08 August 2016

Publication Date:
17 January 2017 (online)

Abstract

Prevention and treatment of Alzheimerʼs disease are urgent problems for elderly people in developed countries. To seek useful compounds that treat, delay the onset, or prevent the development of Alzheimerʼs disease, we screened natural resources using the cyclic AMP response element-dependent transcription in the PC12 cell line. We previously found that honey bee royal jelly stimulates the cyclic AMP response element-dependent transcription activity in PC12 cells. Here, we report that R-limonene, a monoterpene, enhanced the royal jelly-induced cyclic AMP response element-dependent transcription activity, whereas R-limonene showed no effect in absence of royal jelly. The enhancement was inhibited by ZM241385, an antagonist for adenosine A2 A receptor. R-limonene also enhanced the cyclic AMP response element-dependent transcription activity activated by adenosine and AMP. Thus, R-limonene represents a novel type of modulator that enhances the CRE-dependent transcription via adenosine A2 A receptor pathway.

* These authors contributed equally to this work.


Supporting Information

 
  • References

  • 1 Tanzi RE, Bertram L. Twenty years of the Alzheimerʼs disease amyloid hypothesis: a genetic perspective. Cell 2005; 120: 545-555
  • 2 Kandel ER. The molecular biology of memory storage: a dialogue between genes and synapses. Science 2001; 294: 1030-1038
  • 3 Nagase H, Omae N, Omori A, Nakagawasai O, Tadano T, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y. Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem Biophys Res Commun 2005; 337: 1330-1336
  • 4 Matsuzaki K, Yamakuni T, Hashimoto M, Haque AM, Shido O, Mimaki Y, Sashida Y, Ohizumi Y. Nobiletin restoring beta-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimerʼs disease model rats. Neurosci Lett 2006; 400: 230-234
  • 5 Nakajima A, Yamakuni T, Haraguchi M, Omae N, Song SY, Kato C, Nakagawasai O, Tadano T, Yokosuka A, Mimaki Y, Sashida Y, Ohizumi Y. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy-induced cholinergic neurodegeneration in mice. J Pharmacol Sci 2007; 105: 122-126
  • 6 Onozuka H, Nakajima A, Matsuzaki K, Shin RW, Ogino K, Saigusa D, Tetsu N, Yokosuka A, Sashida Y, Mimaki Y, Yamakuni T, Ohizumi Y. Nobiletin, a citrus flavonoid, improves memory impairment and Abeta pathology in a transgenic mouse model of Alzheimerʼs disease. J Pharmacol Exp Ther 2008; 326: 739-744
  • 7 Yabuki Y, Ohizumi Y, Yokosuka A, Mimaki Y, Fukunaga K. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice. Neuroscience 2014; 259: 126-141
  • 8 Fujiwara H, Kogure A, Sakamoto M, Yamakuni T, Mimaki Y, Murata K, Hitomi N, Yamaguchi K, Ohizumi Y. Honeybee royal jelly and nobiletin stimulate CRE-mediated transcription in ERK-independent and -dependent fashions, respectively, in PC12D cells. J Pharmacol Sci 2011; 116: 384-387
  • 9 Hattori N, Nomoto H, Mishima S, Inagaki S, Goto M, Sako M, Furukawa S. Identification of AMP N1-oxide in royal jelly as a component neurotrophic toward cultured rat pheochromocytoma PC12 cells. Biosci Biotechnol Biochem 2006; 70: 897-906
  • 10 Stone TW, Ceruti S, Abbracchio MP. Adenosine receptors and neurological disease: neuroprotection and neurodegeneration. Handb Exp Pharmacol 2009; 193: 535-587
  • 11 Düster R, Prickaerts J, Blokland A. Purinergic signaling and hippocampal long-term potentiation. Curr Neuropharmacol 2014; 12: 37-43
  • 12 de Mendonça A, Ribeiro JA. Endogenous adenosine modulates long-term potentiation in the hippocampus. Neuroscience 1994; 62: 385-390
  • 13 Wang JH, Ma YY, van den Buuse M. Improved spatial recognition memory in mice lacking adenosine A2 A receptors. Exp Neurol 2006; 199: 438-445
  • 14 Park HM, Lee JH, Yaoyao J, Jun HJ, Lee SJ. Limonene, a natural cyclic terpene, is an agonistic ligand for adenosine A(2 A) receptors. Biochem Biophys Res Commun 2011; 404: 345-348
  • 15 Yamaguchi K. Innovation of natural beekeeping and quality control of bee products for promising apiculture. 1. Current problems of beekeeping and recurrence of natural bee-culture for resolution of the problems. J Yunnan Agric Univ 2004; 19: 322-329