Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang
Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang
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DOI：
10.1016/j.pbb.2008.02.014
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Li, Yun-Feng
中科院分区：
文献类型：
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作者：
An, Lei;Zhang, You-Zhi;Li, Yun-Feng
小补心汤是一种传统的中药汤剂，在中国用于治疗抑郁症已有数百年的历史。本研究旨在探讨从XBXT提取物中分离得到的总黄酮（XBXT-2）的抗抑郁样作用及其单胺能机制。在本研究中，单次XBXT-2（25、50、100 mg/kg，p.o.）给药显著增强了5-羟色氨酸（5-HTP，5-羟色胺的代谢前体）诱导的小鼠头部抽搐反应，并且还减少了小鼠悬尾试验中的不动时间，这完全被对氯苯丙氨酸（PCPA，5-羟色胺合成的抑制剂）预处理所阻止。然而，单用XBXT-2处理对育亨宾毒性和高剂量阿朴吗啡诱导的小鼠体温降低没有影响。这些结果表明，用XBXT-2急性处理产生肾上腺素能，但不产生去甲肾上腺素能活化。此外，慢性XBXT-2（25、50 mg/kg，p.o.，28天）治疗显著逆转了慢性轻度应激（CMS）大鼠的抑郁样行为，包括蔗糖偏好降低、运动活动不足和新奇抑制进食潜伏期延长。此外，XBXT-2使CMS大鼠海马和前额皮质中神经递质的变化正常化，包括降低5-HT及其代谢物5-HIAA水平。这些发现证实了XBXT-2在大鼠CMS模型中的抗抑郁样作用，这可能主要基于其β-胡萝卜素能激活。(C)2008年爱思唯尔公司All rights reserved.
Xiaobuxin-Tang (XBXT), a traditional Chinese herbal decoction, has been used for the treatment of depressive disorders for centuries in China. Herein, we explored the antidepressant-like effect and its monoaminergic mechanism of the total flavonoids (XBXT-2) isolated from the extract of XBXT. In present study, single XBXT-2 (25, 50, 100 mg/kg, p.o.) administration significantly potentiated the mouse head-twitch response induced by 5-hydroxytryptophan (5-HTP, a metabolic precursor to serotonin), and also, decreased the immobility time in mouse tail suspension test, which was completely prevented by p-chlorophenylalanine (PCPA, an inhibitor of serotonin synthesis) pretreatment. However, single treatment with XBXT-2 had no effect on yohimbine toxicity and high dose of apomorphine-induced hypothermia in mice. These results indicated that acute treatment with XBXT-2 produced serotonergic, but not noradrenergic activation. In addition, chronic XBXT-2 (25, 50 mg/kg, p.o., 28 days) treatments significantly reversed the depressive-like behaviors in chronically mildly stressed (CMS) rats, including the reduced sucrose preference, deficient locomotor activity and prolonged latency to novelty-suppressed feeding. Furthermore, XBXT-2 normalized the neurotransmitter changes, including the decreased serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in hippocampus and prefrontal cortex in CMS rats. These findings confirm the antidepressant-like effect of XBXT-2 in CMS model of rats, which may be primarily based on its serotonergic activation. (C) 2008 Elsevier Inc. All rights reserved.