title: Antidepressant-Like Effect of Isorhynchophylline in Mice.
abstract: Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Miq) Miq ex Havil. (Rubiaceae). Previous studies in our laboratory have revealed that IRN possesses potent neuroprotective effects in different models of Alzheimer's disease. However, the antidepressant-like effects of IRN are remained unclear. The present study aims to evaluate the antidepressant-like effects of IRN. The antidepressant-like effects of IRN was determined by using animal models of depression including forced swimming and tail suspension tests. The acting mechanism was explored by determining the effect of IRN on the levels of monoamine neurotransmitters and the activities of monoamine oxidases. Intragastric administration of IRN at 10, 20 and 40 mg/kg for 7 days caused a significant reduction of immobility time in both forced swimming and tail suspension tests, while IRN did not stimulate locomotor activity in the open-field test. In addition, IRN treatment antagonized reserpine-induced ptosis and significantly enhanced the levels of monoamine neurotransmitters including norepinephrine (NE) and 5-hydroxytryptamine (5-HT), and the activity of monoamine oxidase A (MAO-A) in the hippocampus and frontal cortex of mice. These results suggest that the antidepressant-like effects of IRN are mediated, at least in part, by the inhibition of monoamine oxidases.
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People's Republic of China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Xian
authors.affiliation: Shenzhen Wellsoon Pharmaceutical Company Limited, Shenzhen, Guangdong, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Fan
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People's Republic of China.
authors.forename: Siu-Po
authors.initials: SP
authors.lastname: Ip
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People's Republic of China.
authors.forename: Qing-Qiu
authors.initials: QQ
authors.lastname: Mao
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People's Republic of China. linzx@cuhk.edu.hk.
authors.forename: Zhi-Xiu
authors.initials: ZX
authors.lastname: Lin
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D019417:Hindlimb Suspension / Q000009:adverse effects / Q000523:psychology; D007103:Immobilization / Q000009:adverse effects; D026121:Indole Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D000078183:Oxindoles; D011897:Random Allocation; D013550:Swimming / Q000523:psychology; D016896:Treatment Outcome; D032070:Uncaria
chemical_list: D000928:Antidepressive Agents; D026121:Indole Alkaloids; D000078183:Oxindoles; C052714:rhyncophylline
keywords: Antidepressant-like effect; Forced swimming test; Isorhynchophylline; Monoamine neurotransmitter; Reserpine antagonism; Tail suspension test