Involvement of nitric oxide (NO) signaling pathway in the antidepressant action of the total flavonoids extracted from Xiaobuxin-Tang

• XBXT-2 presented antidepressant-like effects in the mouse forced swim test (FST).
• The antidepressant effect of XBXT-2 was reversed by pretreatment with l-arginine.
• 7-Nitroindazole potentiated the antidepressant effect of XBXT-2.

Our previous studies have demonstrated that the total flavonoids (XBXT-2) isolated from the extract of Xiaobuxin-Tang (XBXT), a traditional Chinese herbal decoction, exerted antidepressant-like effects. Recently, accumulating studies have suggested that l-arginine-NO is implicated in the regulation of depression. Therefore, the aim of current study attempts to explore the involvement of l-arginine-NO pathway in the antidepressant-like effect of XBXT-2 in the mouse forced swim test (FST). Our results showed that the antidepressant-like action of XBXT-2 (100 mg/kg, i.g.) was reversed by pretreatment with l-arginine (a nitric oxide precursor, 750 mg/kg, i.p.). While co-administration of aminoguanidine (a specific inducible NOS inhibitor, 40, 80 mg/kg, i.p.) and sub-effective dose of XBXT-2 (50 mg/kg, i.g.) did not significantly alter the immobility in FST. In contrast, combined administration of 7-nitroindazole (a specific neuronal NOS inhibitor, 50 mg/kg, i.p.) potentiated the antidepressant-like effect of non-effective doses of XBXT-2 (50 mg/kg, i.g.). Meanwhile, NO modulators were devoid of any locomotor effects on the animals. In conclusion, the antidepressant-like action of XBXT-2 may be involvement of NO signaling pathway.