Xylocarpin H, a Limonoid of <i>Xylocarpus granatum</i>, Produces Antidepressant-Like Activities in Mice

Abstract

Major depression is a common psychiatric disorder worldwide that imposes a substantial health burden on society. Currently available antidepressants do not meet the clinical needs. Here, we report that Xylocarpin H, a limonoid of Xylocarpus granatum , has antidepressant-like effects in mouse forced swimming and tail suspension tests, two validated models of depression. 7-day oral administration of Xylocarpin H resulted in dose-dependent decreases immobility duration within the dose range of 15 - 50 mg/kg. Xylocarpin H dose-dependently increases the time spent in the central zone at doses of 5 - 50 mg/kg in locomotion activity test. In addition, 7-day treatment Xylocarpus H at 15 and 50 mg/kg doses significantly decreases levels of serum corticosterone and adrenocorticotropic hormone (ACTH) following the acute stress of forced swimming test. Furthermore, these effective doses of Xylocarpin H do not affect locomotor activity and levels of serum corticosterone and ACTH in the absence of stress. In summary, the present study, for the first time, demonstrates that Xylocarpin H exerts antidepressant-like effects in mouse behavioral models of depression, likely by inhibiting HPA axis systems. These data provide primarily basis for developing Xylocarpin H as a novel antidepressant candidate for the treatment of depression and stress related disorders.