The in vivo material basis responsible for the antidepressant activity of saffron glycoside-Ⅰ
AIM:To study the in vivo material ba-sis that is involved in the rapid antidepressant ef-fects of saffron glycoside-Ⅰ,so as to provide evi-dences to facilitate the interpreting the inconsis-tency of PK-PD,and the exploring the underlying mechanism.METHODS:The antidepressant effica-cy of saffron glycoside-Ⅰ and saffron aglycone was evaluated by investigating depressive-like behaviors such as Sucrose Preference Test(SPT),Social Inter-action Test(SIT),Tail Suspension test(TST),and the Forced Swim Test(FST)in mice induced by Chronic Unpredictable Stress(CUMS)and Chronic Social De-feat Stress(CSDS).The LPS-induced model of in-flammation was used to investigate the regulatory effect of saffron glycoside-Ⅰ on primary inflammato-ry factors.The regulation of saffron glycoside-Ⅰ and saffron aglycone on small molecules and neu-rotransmitters in blood and intestine were further studied by non-targeting metabolomics and target-ing metabolites of neural transmitters based on HPLC-qTOF/MS and LC/MS-MS techniques.RE-SULTS:Saffron glycoside-Ⅰ and its aglycone showed rapid and efficient antidepressant effects,and they significantly improved the performance of CSDS mice on SIT,TST,and FST.Saffron glycoside-Ⅰ did not show obvious effect on reducing LPS-induced inflammatory factors of IL-6 and TNF-α.On the con-trary,typical anti-inflammatory drug components of paeoniflorin,silybin and magnesium isoglycyrrhi-zinate significantly reversed the elevation of IL-6 and TNF-α induced by LPS,but they could not res-cue the depressant behaviors of CSDS mice.Metab-olomic study revealed perturbation of metabolic phenotype,small molecules and neural transmit-ters in plasma and gut contents of both CUMS and CSDS mice.To a large content,and Saffron glyco-side-Ⅰ and saffron aglycone modulated metabolic phenotype,similar to the normal controls.Saffron aglycone successfully regulated a variety of metab-olites,metabolites associated in purine pathway,and transmitters,such as 5-HT,y-GABA,glutamic acid and norepinephrine that were perturbed in plasma and gut contents in CSDS mice.CONCLU-SION:Saffron aglycone shows a rapid antidepres-sant effect similar to saffron glycoside-Ⅰ,the anti-depressant effect of saffron glycoside-Ⅰ is closely as-sociated with its primary metabolite saffron agly-cone in vivo.The antidepressant effect of saffron aglycone is involved in its regulation effects on en-dogenous small molecules and neurotransmitters in the circulatory system and intestinal tract of de-pression model mice,instead of that on inhibition on inflammatory factors.
depressionsaffron glycoside-Ⅰsaf-fron aglyconechronic social defeat stress(CSDS)chronic chronic unpredictable stress(CUMS)
万方数据
维普
