Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang.
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.
An
Lei
L
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
Zhang
You-Zhi
YZ
Yu
Neng-Jiang
NJ
Liu
Xin-Min
XM
Zhao
Nan
N
Yuan
Li
L
Li
Yun-Feng
YF
D000818:Animals; D000928:Antidepressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001058:Apomorphine / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000188:drug therapy; D015016:Yohimbine / Q000633:toxicity
D000928:Antidepressive Agents; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D010936:Plant Extracts; D015016:Yohimbine; D012701:Serotonin; D001058:Apomorphine; D010134:Fenclonine