Nutr Res Pract.  2010 Aug;4(4):270-275.

Anti-stress effects of ginseng via down-regulation of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) gene expression in immobilization-stressed rats and PC12 cells

Affiliations
  • 1Department of Nutritional Science and Food Management, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea. yhmoon@ewha.ac.kr
  • 2Food BioNano Research Group, Korea Food Research Institute, Gyeonggi 463-746, Korea.
  • 3Department of Food & Nutrition, Korea University, Seoul 136-703, Korea.

Abstract

Catecholamines are among the first molecules that displayed a kind of response to prolonged or repeated stress. It is well established that long-term stress leads to the induction of catecholamine biosynthetic enzymes such as tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) in adrenal medulla. The aim of the present study was to evaluate the effects of ginseng on TH and DBH mRNA expression. Repeated (2 h daily, 14 days) immobilization stress resulted in a significant increase of TH and DBH mRNA levels in rat adrenal medulla. However, ginseng treatment reversed the stress-induced increase of TH and DBH mRNA expression in the immobilization-stressed rats. Nicotine as a ligand of the nicotinic acetylcholine receptor (nAChR) in adrenal medulla stimulates catecholamine secretion and activates TH and DBH gene expression. Nicotine treatment increased mRNA levels of TH and DBH by 3.3- and 3.1-fold in PC12 cells. The ginseng total saponin exhibited a significant reversal in the nicotine-induced increase of TH and DBH mRNA expression, decreasing the mRNA levels of TH and DBH by 57.2% and 48.9%, respectively in PC12 cells. In conclusion, immobilization stress induced catecholamine biosynthetic enzymes gene expression, while ginseng appeared to restore homeostasis via suppression of TH and DBH gene expression. In part, the regulatory activity in the TH and DBH gene expression of ginseng may account for the anti-stress action produced by ginseng.

Keyword

Stress; catecholamine; ginseng; tyrosine hydroxylase; dopamine beta-hydroxylase

MeSH Terms

Adrenal Medulla
Animals
Catecholamines
Dopamine
Dopamine beta-Hydroxylase
Down-Regulation
Gene Expression
Homeostasis
Immobilization
Nicotine
Panax
PC12 Cells
Rats
Receptors, Nicotinic
RNA, Messenger
Saponins
Tyrosine
Tyrosine 3-Monooxygenase
Catecholamines
Dopamine
Dopamine beta-Hydroxylase
Nicotine
RNA, Messenger
Receptors, Nicotinic
Saponins
Tyrosine
Tyrosine 3-Monooxygenase

Figure

  • Fig. 1 Effect of ginseng on body weights in immobilization stressed rats. The groups are control (C), immobilization stress (S), and ginseng with immobilization stress (GS). The immobilization stress was induced daily for 2 hr of each day for 2 weeks. The ginseng with immobilization stress group was treated with ginseng (200 mg/kg BW) dissolved in water after the application of immobilization stress. Results are represented as mean ± SE (n = 6). Values with different superscript letter are significantly different, P < 0.05.

  • Fig. 2 Effect of ginseng on serum corticosterone levels in immobilization stressed rats. The serum corticosterone levels were measured as described in Materials and Methods. Each bar represents the mean ± SE in each group; control (C), immobilization stress (S), and ginseng with immobilization stress (GS). Results are represented as mean ± SE (n = 6). Values with different superscript letter are significantly different, P < 0.05.

  • Fig. 3 Effect of ginseng on the expression of genes involved catecholamine biosynthesis in adrenal gland. Total RNA extracted from adrenal gland was used for mRNA expression analysis of TH (A) and DBH (B) by quantitative real-time PCR. The groups are control (C), immobilization stress (S), and ginseng with immobilization stress (GS). The immobilization stress was induced daily for 2 hr of each day for 2 weeks. The ginseng with immobilization stress group was treated with ginseng (200 mg/kg BW) dissolved in water after the application of immobilization stress. Values are expressed as the fold-change over control as mean ± SE (n = 4). Values with different superscript letter are significantly different, P < 0.05.

  • Fig. 4 Effect of GTS on the expression of genes involved catecholamine biosynthesis in PC12 cells. The groups are control (C), nicotine (N), GTS with nicotine (GN). PC12 cells were treated with 10 uM nicotine in the presence or absence of 10 µg/ml GTS for 12h. The mRNAs of TH (A) and DBH (B) were measured by quantitative real-time RT-PCR. Values are expressed as the fold-change over control and as the mean ± SE (n = 3). Values with different superscript letter are significantly different, P < 0.05.


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