Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: Possible role of L-arginine-NO-cGMP pathway and BDNF levels
Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: Possible role of L-arginine-NO-cGMP pathway and BDNF levels
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DOI：
10.1016/j.brainresbull.2014.03.004
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发表时间：
2014-05-01
影响因子：
3.8
通讯作者：
Jesse, Cristiano Ricardo
中科院分区：
文献类型：
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作者：
Donato, Franciele;de Gomes, Marcelo Gomes;Jesse, Cristiano Ricardo
橙皮苷（4 '-甲氧基-7-O-芸香糖基-3'，5-二羟基黄烷酮）是一种天然存在的黄烷酮糖苷，先前已显示通过调节肾上腺素能5-HT 1A和κ-阿片受体产生抗抑郁样作用。在这项研究中，其抗抑郁样作用的信号转导机制进行了进一步评估，通过调查在急性和慢性治疗。结果显示，橙皮苷或橙皮素（0.1、0.3和lmg/kg，腹腔内，i. p.）在小鼠悬尾试验（TST）中具有抗抑郁样作用，而在旷场试验中不改变运动活性。用L-精氨酸（一氧化氮（NO）前体）、西地那非（磷酸二酯酶5抑制剂）或S-亚硝基-N-乙酰基-青霉胺（NO供体）预处理显著逆转了TST中橙皮苷（0.3 mg/kg）急性处理引起的不动时间减少。橙皮苷（0.01 mg/kg，急性治疗亚有效剂量）与N-G-硝基-L-精氨酸（一氧化氮合酶（NOS）抑制剂）或7-硝基吲唑（神经元NOS抑制剂）在TST中产生相加的抗抑郁样作用。用亚甲蓝（NOS/可溶性鸟苷酸环化酶（sGC）的抑制剂）或ODQ（一种特异性抑制剂sGS）预处理动物，在TST中与橙皮苷产生累加效应。橙皮苷在急性（1毫克/公斤）和慢性（0.1，0.3和1毫克/公斤）治疗引起了显着降低小鼠海马中的硝酸盐/亚硝酸盐（NOx）水平。橙皮苷（0.3和1 mg/kg）的慢性治疗也导致海马脑源性神经营养因子（BDNF）水平的增加。以上结果提示橙皮苷的抗抑郁作用可能是通过抑制L-精氨酸-NO-cGMP通路和增加海马BDNF水平而实现的。(C)2014爱思唯尔公司All rights reserved.
Hesperidin (4'-methoxy-7-O-rutinosyl-3',5-dihydroxyflavanone), a naturally occurring flavanone glycoside, was previously shown to produce an antidepressant-like effect with modultation of the serotonergic 5-HT1A and kappa-opioid receptors. In this study, the signaling mechanisms underlying their antidepressant-like effects were further evaluated by investigating in acute and chronic treatments. Results showed that chronic treatment of hesperidin or hesperitin (0.1, 0.3 and 1 mg/kg, intraperitoneal, i.p.) have an antidepressant-like effect in the mouse tail suspension test (TST) without modified the locomotor activity in the open field test. Pretreatment with L-arginine (a nitric oxide (NO) precursor), sildenafil (a phosphodiesterase 5 inhibitor) or S-nitroso-N-acetyl-penicillamine (a NO donor) significantly reversed the reduction in immobility time elicited by acute treatment with hesperidin (0.3 mg/kg) in the TST. Hesperidin (0.01 mg/kg, a sub-effective dose in acute treatment) produced an additive antidepressant-like effect with N-G-nitro-L-arginine (an inhibitor of nitric oxide synthase (NOS)) or 7-nitroindazole (a neuronal NOS inhibitor) in the TST. Pretreatment of animals with methylene blue (an inhibitor of NOS/soluble guanylate cyclase (sGC)) or ODQ (a specific inhibitor sGS) caused an additive effect with hesperidin in the TST. Hesperidin in the acute (1 mg/kg) and chronic (0.1, 0.3 and 1 mg/kg) treatments caused a significant decrease in nitrate/nitrite (NOx) levels in the hippocampus of mice. Chronic treatment with hesperidin (0.3 and 1 mg/kg) also resulted in an increase in hippocampal brain-derived neurotrophic factor (BDNF) levels. These results demonstrated that the antidepressant-like effect of hesperidin is likely mediated by inhibition of L-arginine-NO-cGMP pathway and by increased of the BDNF levels in hippocampus. (C) 2014 Elsevier Inc. All rights reserved.