Antidepressant-like effects of penta-acetyl geniposide in chronic unpredictable mild stress-induced depression rat model: Involvement of inhibiting neuroinflammation in prefrontal cortex and regulating hypothalamic-pituitaryadrenal axis

摘要

We previously reported that penta-acetyl geniposide ((Ac)(5)GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide, a major active component of Gardenia jasminoides Ellis. This study demonstrated the antidepressant-like effects of (Ac)(5)GP and its involved mechanisms using a rat depression model caused by chronic unpredictable mild stress (CUMS). Behavioral tests including sucrose preference, open field and forced swimming were applied to evaluate depression symptoms. IL-1 beta, IL-6 and TNF-alpha mRNA and protein levels in prefrontal cortex (PFC) were respectively measured by quantitative PCR and ELISA. The protein levels of I kappa B alpha, p-I kappa B alpha, NF-kappa B p65, NLRP3, pro- and mature-IL-1 beta in PFC were determined by western blot. The activity of hypothalamic-pituitaryadrenal (HPA) axis was also measured. (Ac)(5)GP treatment alleviated the CUMS-induced depressive-like behaviors in rats, as indicated by increased sucrose intake, increased total crossing and rearing numbers, improved central activity and reduced immobility time. (Ac)(5)GP reversed the CUMS-induced elevations of IL-1 beta, IL-6 and TNF-alpha mRNA and protein levels in PFC. (Ac)(5)GP reduced degradation and phosphorylation of I kappa B alpha and protein level of nuclear NF-kappa B p65 in PFC. (Ac)(5)GP also decreased the mRNA and protein levels of NLRP3 and reduced the ratio of mature-IL-1 beta protein over total IL-1 beta protein (pro-IL-1 beta + mature-IL-1 beta) in PFC. Moreover, (Ac)(5)GP reduced serum levels of adrenocorticotropic hormone/corticosterone and mRNA level of hypothalamic corticotrophin-releasing hormone. In conclusion, (Ac)(5)GP treatment improved the depressive-like behaviors in CUMS rats perhaps by suppressing neuroinflanunation in PFC and inhibiting activations of NF-kappa B and NLRP3 and also attenuating HPA axis hyperactivity.