Xian Yan-Fang, Fan Ding, Ip Siu-Po, Mao Qing-Qiu, Lin Zhi-Xiu
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, People's Republic of China.
Shenzhen Wellsoon Pharmaceutical Company Limited, Shenzhen, Guangdong, China.
Neurochem Res. 2017 Feb;42(2):678-685. doi: 10.1007/s11064-016-2124-5. Epub 2016 Nov 30.
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.
异钩藤碱（IRN）是一种氧化吲哚生物碱，已被确定为钩藤（茜草科）生物活性的主要活性成分。我们实验室之前的研究表明，IRN在不同的阿尔茨海默病模型中具有强大的神经保护作用。然而，IRN的抗抑郁样作用仍不清楚。本研究旨在评估IRN的抗抑郁样作用。通过使用包括强迫游泳和悬尾试验在内的抑郁动物模型来确定IRN的抗抑郁样作用。通过测定IRN对单胺类神经递质水平和单胺氧化酶活性的影响来探讨其作用机制。以10、20和40mg/kg的剂量连续7天灌胃给予IRN，在强迫游泳和悬尾试验中均显著减少了不动时间，而在旷场试验中IRN并未刺激运动活性。此外，IRN治疗拮抗了利血平诱导的眼睑下垂，并显著提高了小鼠海马和额叶皮质中去甲肾上腺素（NE）和5-羟色胺（5-HT）等单胺类神经递质的水平以及单胺氧化酶A（MAO-A）的活性。这些结果表明，IRN的抗抑郁样作用至少部分是由抑制单胺氧化酶介导的。
