title: Gintonin enhances performance of mice in rotarod test: Involvement of lysophosphatidic acid receptors and catecholamine release.
abstract: Ginseng has a long history of use as a tonic for restoration of vigor. One example of ginseng-derived tonic effect is that it can improve physical stamina under conditions of stress. However, the active ingredient and the underlying molecular mechanism responsible for the ergogenic effect are unknown. Recent studies show that ginseng contains a novel ingredient, gintonin, which consists of a unique class of herbal-medicine lysophosphatidic acids (LPAs). Gintonin activates G protein-coupled LPA receptors to produce a transient [Ca(2+)]i signal, which is coupled to diverse intra- and inter-cellular signal transduction pathways that stimulate hormone or neurotransmitter release. However, relatively little is known about how gintonin-mediated cellular modulation is linked to physical endurance. In the present study, systemic administration of gintonin, but not ginsenosides, in fasted mice increased blood glucose concentrations in a dose-dependent manner. Gintonin treatment elevated blood glucose to a maximum level after 30min. This elevation in blood glucose level could be abrogated by the LPA1/3 receptor antagonist, Ki16425, or the β-adrenergic receptor antagonist, propranolol. Furthermore, gintonin-dependent enhanced performance of fasted mice in rotarod test was likewise abrogated by Ki16425. Gintonin also elevated plasma epinephrine and norepinephrine concentrations. The present study shows that gintonin mediates catecholamine release through activation of the LPA receptor and that activation of the β-adrenergic receptor is coupled to liver glycogenolysis, thereby increasing the supply of glucose and enhancing performance in the rotarod test. Thus, gintonin acts via the LPA-catecholamine-glycogenolysis axis, representing a candidate mechanism that can explain how ginseng treatment enhances physical stamina.
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Byung-Hwan
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Physical Education, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Jisu
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, College of Veterinary Medicine, Konkuk University, Seoul 143-701, South Korea.
authors.forename: Ra Mi
authors.initials: RM
authors.lastname: Lee
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Sun-Hye
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea.
authors.forename: Hyeon-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmaceutical Engineering, College of Health Sciences, Sangji University, Wonju 220-702, South Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, South Korea.
authors.forename: Myung Koo
authors.initials: MK
authors.lastname: Lee
authors.affiliation: Department of Veterinary Surgery, Chonnam National University College of Veterinary Medicine, Gwangju 500-757, South Korea.
authors.forename: Chun-Sik
authors.initials: CS
authors.lastname: Bae
authors.affiliation: Neuropsychopharmacology and toxicology program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Center for Neuroscience, Korea Institute of Science and Technology, Seoul 139-791, South Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Rhim
authors.affiliation: Department of Physical Education, Konkuk University, Seoul 143-701, South Korea. Electronic address: exercise@konkuk.ac.kr.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Lim
authors.affiliation: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine Konkuk University, Seoul 143-701, South Korea. Electronic address: synah@konkuk.ac.kr.
authors.forename: Seung-Yeol
authors.initials: SY
authors.lastname: Nah
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D005215:Fasting; D050261:Glycogenolysis; D008297:Male; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood; D010805:Physical Conditioning, Animal; D010807:Physical Endurance / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045442:Rotarod Performance Test
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002395:Catecholamines; D010936:Plant Extracts; D049368:Receptors, Lysophosphatidic Acid; C000603040:gintonin; D009638:Norepinephrine; D004837:Epinephrine
keywords: Blood glucose; Catecholamines; Ginseng; Gintonin; Rotarod performance