Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: Absorbed MH accounts for FA\'s anti-depressant and prokinetic efficacy in acutely-stressed rats, primarily via 5-HT3/GHSR shared regulation.
OBJECTIVE: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: Absorbed MH accounts for FA\'s anti-depressant and prokinetic efficacy in acutely-stressed rats, primarily via 5-HT3/GHSR shared regulation.
摘要：
背景：樟脑（FA），著名的植物药，已被用来唤起抗抑郁药和促动力多功能。其中,系统地识别生物活性成分和提及的机制对于FA至关重要。
目的：这项研究计划回答“2W”（什么和为什么），例如哪些组件和途径有助于FA的多功能。我们旨在确定生物活性化合物作为打开FA的多功能锁的关键，分子机制是它们自然匹配的锁芯。
方法：测定FA提取物的植物化学成分含量，并使用液相色谱-质谱（LC-MS）在用FA预处理的大鼠中鉴定化合物。贡献策略用于评估具有机制的模型大鼠中生物活性化合物的功效（剂量=其在FA中的含量）。通过7.0T功能磁共振成像-血氧水平依赖性（fMRI-BOLD）确定脑功能区的变化。
结果：检测到8种植物化学物质含量，在大鼠体内仅鉴定出六种成分。Meranzin水合物+橙皮苷(MH),作为FA的主要贡献者，发挥了抗抑郁和促动力作用(不动时间指标的改善，胃排空,肠道运输，CRH,ghrelin,ACTH,DA,NA,5-HT,CORT,和5-HT3）通过调节5-HT3/生长激素促分泌素受体（GHSR）途径。这些结果通过5-HT2A进行了验证，5-HT3和GHSR受体拮抗剂结合分子对接。MH恢复了左伏隔核的过度BOLD激活，左侧call体和下丘脑视前区。
结论：吸收的MH在急性应激大鼠中占FA的抗抑郁和促动力功效，主要通过5-HT3/GHSR共享监管。
目的：这项研究计划回答“2W”（什么和为什么），例如哪些组件和途径有助于FA的多功能。我们旨在确定生物活性化合物作为打开FA的多功能锁的关键，分子机制是它们自然匹配的锁芯。
方法：测定FA提取物的植物化学成分含量，并使用液相色谱-质谱（LC-MS）在用FA预处理的大鼠中鉴定化合物。贡献策略用于评估具有机制的模型大鼠中生物活性化合物的功效（剂量=其在FA中的含量）。通过7.0T功能磁共振成像-血氧水平依赖性（fMRI-BOLD）确定脑功能区的变化。
结果：检测到8种植物化学物质含量，在大鼠体内仅鉴定出六种成分。Meranzin水合物+橙皮苷(MH),作为FA的主要贡献者，发挥了抗抑郁和促动力作用(不动时间指标的改善，胃排空,肠道运输，CRH,ghrelin,ACTH,DA,NA,5-HT,CORT,和5-HT3）通过调节5-HT3/生长激素促分泌素受体（GHSR）途径。这些结果通过5-HT2A进行了验证，5-HT3和GHSR受体拮抗剂结合分子对接。MH恢复了左伏隔核的过度BOLD激活，左侧call体和下丘脑视前区。
结论：吸收的MH在急性应激大鼠中占FA的抗抑郁和促动力功效，主要通过5-HT3/GHSR共享监管。
