An Lei, Zhang You-Zhi, Yu Neng-Jiang, Liu Xin-Min, Zhao Nan, Yuan Li, Li Yun-Feng
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
Pharmacol Biochem Behav. 2008 Jun;89(4):572-80. doi: 10.1016/j.pbb.2008.02.014. Epub 2008 Mar 25.
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.
逍遥散（XBXT）是一种传统的中药汤剂，在中国已用于治疗抑郁症数百年。在此，我们探讨了从逍遥散提取物中分离出的总黄酮（XBXT-2）的抗抑郁样作用及其单胺能机制。在本研究中，单次给予XBXT-2（25、50、100mg/kg，口服）可显著增强5-羟色氨酸（5-HTP，血清素的代谢前体）诱导的小鼠头部抽搐反应，并且还可减少小鼠悬尾试验中的不动时间，而对氯苯丙氨酸（PCPA，血清素合成抑制剂）预处理可完全阻断此作用。然而，单次给予XBXT-2对小鼠育亨宾毒性和高剂量阿扑吗啡诱导的体温过低没有影响。这些结果表明，急性给予XBXT-2可产生血清素能激活，但不产生去甲肾上腺素能激活。此外，慢性给予XBXT-2（25、50mg/kg，口服，28天）可显著逆转慢性轻度应激（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摄食潜伏期延长。此外，XBXT-2使神经递质变化正常化，包括CMS大鼠海马和前额叶皮质中血清素（5-HT）及其代谢产物5-羟吲哚乙酸（5-HIAA）水平降低。这些发现证实了XBXT-2在大鼠CMS模型中的抗抑郁样作用，其可能主要基于其血清素能激活。
