2. Academic Validation
  3. Phytomedicine Fructus Aurantii-derived two absorbed compounds unlock antidepressant and prokinetic multi-functions via modulating 5-HT3/GHSR

Phytomedicine Fructus Aurantii-derived two absorbed compounds unlock antidepressant and prokinetic multi-functions via modulating 5-HT3/GHSR

  • J Ethnopharmacol. 2024 Jan 5:117703. doi: 10.1016/j.jep.2024.117703.
Qiulong Zhao 1,  Jin Liu 2,  Li Chen 1,  Zhao Gao 1,  Muhai Lin 2,  Yun Wang 2,  Zhe Xiao 2,  Yi Chen 2,  Xi Huang 3
Affiliations

Affiliations

  • 1 Institute of TCM-Related Comorbid Depression, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 Medical College, Xiamen University, School of Medicine, Xiamen, 361102, China.
  • 3 Institute of TCM-Related Comorbid Depression, Nanjing University of Chinese Medicine, Nanjing 210023, China; Medical College, Xiamen University, School of Medicine, Xiamen, 361102, China. Electronic address: 290606@njucm.edu.cn.
PMID: 38185260 DOI: 10.1016/j.jep.2024.117703
Abstract

Ethnopharmacological relevance: 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.

Aim of the study: 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.

Materials and 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 contents 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).

Result: 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.

Conclusion: Absorbed MH accounts for FA's anti-depressant and prokinetic efficacy in acutely-stressed rats, primarily via 5-HT3/GHSR shared regulation.

Keywords

5-HT(3); Anti-depressant; Blood oxygen level-dependent; Fructus aurantii; GHSR; Hesperidin; Meranzin hydrate; Prokinetic.

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