title: The discovery of Yuanzhi-1, a triterpenoid saponin derived from the traditional Chinese medicine, has antidepressant-like activity.
abstract: Yuanzhi, the dried root of Polygala tenuifolia Willd., is a well-known traditional Chinese medicine used for its sedative, antipsychotic, cognitive improving, neuroprotective, and antidepressant effects. The present study was designed to screen and identify the antidepressant-like effect of six triterpenoid saponin components derived from Yuanzhi (Yuanzhi-1 to Yuanzhi-6) using in vitro radioligand receptor binding assays and in vivo behavioral tests. Yuanzhi-1, -3, -5 and -6 were shown to have antidepressant-like activity in the tail suspension test and forced swim test in mice, with no stimulant effect on locomotor activity. The minimal effective dose of Yuanzhi-1 (2.5 mg/kg) was lower than that of duloxetine (5mg/kg), a serotonin and norepinephrine reuptake inhibitor commonly used in the treatment of depression. Yuanzhi-1 (1 nM) had a high affinity for serotonin, norepinephrine and dopamine transporters. Acute toxicity tests indicated that the LD50 of Yuanzhi-1 (86.5mg/kg) was similar to that of duloxetine (73.2 mg/kg). These findings demonstrate that Yuanzhi-1 has a potential to be a novel triple monoamine reuptake inhibitor of antidepressant-like activity.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Zeng-liang
authors.initials: ZL
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Nana
authors.initials: N
authors.lastname: Gao
authors.affiliation: Pingdu People's Hospital, Qingdao 266700, PR China.
authors.forename: Jian-rui
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Xiao-rong
authors.initials: XR
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Hong-xia
authors.initials: HX
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China.
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, PR China. Electronic address: 7810906@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015283:Citalopram / Q000493:pharmacokinetics; D003042:Cocaine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008516:Medicine, Chinese Traditional; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use*; D013550:Swimming / Q000523:psychology; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D000928:Antidepressive Agents; D026901:Membrane Transport Proteins; D012503:Saponins; C000604075:yuanzhi-1; D005473:Fluoxetine; D015283:Citalopram; D014316:Tritium; C011386:nisoxetine; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine
keywords: Antidepressant; Depression; Traditional Chinese medicine; Triple reuptake inhibitor; Yuanzhi