%0 Journal Article
%T Phytomedicine Fructus Aurantii-derived two absorbed compounds unlock antidepressant and prokinetic multi-functions via modulating 5-HT3/GHSR.
%A Zhao Q
%A Liu J
%A Chen L
%A Gao Z
%A Lin M
%A Wang Y
%A Xiao Z
%A Chen Y
%A Huang X
%J J Ethnopharmacol
%V 323
%N 0
%D 2024 Apr 6
%M 38185260
%F 5.195
%R 10.1016/j.jep.2024.117703
%X <B>BACKGROUND: </B>Fructus Aurantii (FA), a well-known phytomedicine, has been employed to evoke antidepressant and prokinetic multi-functions. Therein, systematically identifying bioactive components and the referred mechanism is essential for FA.<BR><B>OBJECTIVE: </B>This study was planned to answer "2 W" (What and Why), such as which components and pathways contribute to FA's multi-functions. We aimed to identify bioactive compounds as the key for opening the lock of FA's multi-functions, and the molecule mechanisms are their naturally matched lock cylinder.<BR><B>METHODS: </B>The phytochemical content of FA extract was determined, and the compounds were identified in rats pretreated with FA using liquid chromatography with mass spectrometry (LC-MS). The contribution strategy was used to assess bioactive compounds' efficacy (doses = their content in FA) in model rats with the mechanism. The changes in functional brain regions were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).<BR><B>RESULTS: </B>Eight phytochemicals' content was detected, and merely six components were identified in rats in vivo. Meranzin hydrate + hesperidin (MH), as the primary contributor of FA, exerted antidepressant and prokinetic effects (improvement of indexes for immobility time, gastric emptying, intestinal transit, CRH, ghrelin, ACTH, DA, NA, 5-HT, CORT, and 5-HT3) by regulating 5-HT3/Growth hormone secretagogue receptor (GHSR) pathway. These results were validated by 5-HT2A, 5-HT3, and GHSR receptor antagonists combined with molecule docking. MH restored the excessive BOLD activation of the left accumbens nucleus, left corpus callosum and hypothalamus preoptic region.<BR><B>CONCLUSIONS: </B>Absorbed MH accounts for FA's anti-depressant and prokinetic efficacy in acutely-stressed rats, primarily via 5-HT3/GHSR shared regulation.