title: Essential Oils from the Medicinal Herbs Upregulate Dopamine Transporter in Rat Pheochromocytoma Cells.
abstract: The dopamine transporter (DAT) protein, a component of the dopamine system, undergoes adaptive neurobiological changes from drug abuse. Prevention of relapse and reduction of withdrawal symptoms are still the major limitations in the current pharmacological treatments of drug addiction. The present study aimed to investigate the effects of essential oils extracted from Elsholtzia ciliata, Shinchim, Angelicae gigantis Radix, and Eugenia caryophyllata, well-known traditional Korean medicines for addiction, on the modulation of dopamine system in amphetamine-treated cells and to explore the possible mechanism underlying its therapeutic effect. The potential cytotoxic effect of essential oils was evaluated in PC12 rat pheochromocytoma cells using cell viability assays. Quantification of DAT, p-CREB, p-MAPK, and p-Akt was done by immunoblotting. DAT was significantly reduced in cells treated with 50 μM of amphetamine in a time-dependent manner. No significant toxicity of essential oils from Elsholtzia ciliata and Shinchim was observed at doses of 10, 25, and 50 μg/mL. However, essential oils from A. gigantis Radix at a dose of 100 μg/mL and E. caryophyllata at doses of 50 and 100 μg/mL showed cytotoxicity. Treatment with GBR 12909, a highly selective DAT inhibitor, significantly increased DAT expression compared with that of amphetamine only by enhancing phosphorylation of mitogen-activated protein kinases (MAPK) and Akt. In addition, essential oils effectively induced hyperphosphorylation of cyclic-AMP response element-binding protein (CREB), MAPK, and Akt, which resulted in DAT upregulation. Our study implies that the essential oils may rehabilitate brain dopamine function through increased DAT availability in abstinent former drug users.
authors: 1 Department of Obstetrics and Gynecology, College of Traditional Korean Medicine, Dongguk University , Gyeongju, Republic of Korea .
authors: Min Sun
authors: MS
authors: Choi
authors: 2 Department of Neuropsychiatry, Graduate School of Traditional Korean Medicine, Dongguk University , Gyeongju, Republic of Korea .
authors: Bang-sub
authors: BS
authors: Choi
authors: 2 Department of Neuropsychiatry, Graduate School of Traditional Korean Medicine, Dongguk University , Gyeongju, Republic of Korea .
authors: Sang Heon
authors: SH
authors: Kim
authors: 3 School of Biomedical Sciences, Charles Sturt University , Bathurst, New South Wales, Australia .
authors: Sok Cheon
authors: SC
authors: Pak
authors: 4 Department of Otoalaryngology, Chonnam National University Medical School , Gwangju, Republic of Korea .
authors: Chul Ho
authors: CH
authors: Jang
authors: 5 Department of Pharmacognosy, College of Pharmacy, Dongguk University-Seoul , Gyeonggi-do, Republic of Korea .
authors: Young-Won
authors: YW
authors: Chin
authors: 5 Department of Pharmacognosy, College of Pharmacy, Dongguk University-Seoul , Gyeonggi-do, Republic of Korea .
authors: Young-Mi
authors: YM
authors: Kim
authors: 1 Department of Obstetrics and Gynecology, College of Traditional Korean Medicine, Dongguk University , Gyeongju, Republic of Korea .
authors: Dong-il
authors: DI
authors: Kim
authors: 6 Dongguk University Research Institute of Biotechnology , Seoul, Republic of Korea .
authors: Songhee
authors: S
authors: Jeon
authors: 2 Department of Neuropsychiatry, Graduate School of Traditional Korean Medicine, Dongguk University , Gyeongju, Republic of Korea .
authors: Byung-Soo
authors: BS
authors: Koo
mesh_terms: D000310:Adrenal Gland Neoplasms; D000818:Animals; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009822:Oils, Volatile / Q000494:pharmacology*; D010673:Pheochromocytoma; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D019966:Substance-Related Disorders / Q000188:drug therapy
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D050483:Dopamine Plasma Membrane Transport Proteins; D009822:Oils, Volatile; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: Akt; CREB; MAPK; addiction; dopamine transporter; essential oils