Gintonin attenuates depressive-like behaviors associated with alcohol withdrawal in mice.
Panax ginseng Meyer extracts have been used to improve mood and alleviate symptoms of depression. However, little is known about the extracts' active ingredients and the molecular mechanisms underlying their reported anti-depressive effects.



Gintonin is an exogenous lysophosphatidic acid (LPA) receptor ligand isolated from P. ginseng. BON cells, an enterochromaffin cell line, and C57BL/6 mice were used to investigate whether gintonin stimulates serotonin release. Furthermore, the effects of gintonin on depressive-like behaviors following alcohol withdrawal were evaluated using the forced swim and tail suspension tests.



Treatment of BON cells with gintonin induced a transient increase in the intracellular calcium concentration and serotonin release in a concentration- and time-dependent manner via the LPA receptor signaling pathway. Oral administration of the gintonin-enriched fraction (GEF) induced an increase in the plasma serotonin concentration in the mice. Oral administration of the GEF in mice with alcohol withdrawal decreased the immobility time in two depression-like behavioral tests and restored the alcohol withdrawal-induced serotonin decrease in plasma levels.



We cannot exclude the possibility that the gintonin-mediated regulation of adrenal catecholamine release in the peripheral system, and acetylcholine and glutamate release in the central nervous system, could also contribute to the alleviation of depressive-like behaviors.



The GEF-mediated attenuation of depressive-like behavior induced by alcohol withdrawal may be mediated by serotonin release from intestinal enterochromaffin cells. Therefore, the GEF might be responsible for the ginseng extract-induced alleviation of depression-related symptoms.
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Hyeon-Joong
HJ
Kim
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Sang-Deuk
SD
Park
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Ra Mi
RM
Lee
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Byung-Hwan
BH
Lee
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
Sun-Hye
SH
Choi
Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju 26339, Republic of Korea.
Sung-Hee
SH
Hwang
Center for Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea.
Hyewhon
H
Rhim
Neuropsychopharmacology and Toxicology program, College of Pharmacy, Kangwon National University, Chunchon 24341, Republic of Korea.
Hyoung-Chun
HC
Kim
Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea. Electronic address: synah@konkuk.ac.kr.
Seung-Yeol
SY
Nah
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D005894:Panax; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D049368:Receptors, Lysophosphatidic Acid / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D002395:Catecholamines; D010936:Plant Extracts; D049368:Receptors, Lysophosphatidic Acid; C000603040:gintonin; D018698:Glutamic Acid; D000109:Acetylcholine; D002118:Calcium
Alcohol withdrawal; Depression; Gintonin; Panax ginseng; Serotonin