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Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 1: 51 - 61

DOI: https://doi.org/10.19852/j.cnki.jtcm.2026.01.005

Original Articles

Ex vivo to in vivo extrapolation of primary absorbed compounds as multifunctional proxies of Zhiqiao (Fructus Aurantii Submaturus)-Houpo (Cortex Magnoliae Officinalis) herb pair

  • Runze ZHOU ,
  • Chendong XU ,
  • Haotian QIAN ,
  • Xi HUANG
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  • Institute of Comorbid Depression, Nanjing University of Chinese Medicine, Nanjing 210023, China

Received date: 2025-01-15

  Accepted date: 2025-05-09

  Online published: 2026-01-28

Supported by

Jiangsu Province’s Colleges and Universities(Integration of Chinese);National Natural Science Foundation of China [Methanism on Molecular and Hippocampus-Thalamus Neurocircuitry of Rapid Prokinetic and Antidepressant by Shugan Following Acute Stress(81973589);The Relationship Between Stress, Ghrelin Signaling, Liver-Soothing and Antidepressant Prokinetic Mechanisms(81573797)

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Abstract

OBJECTIVE: To eliminate ineffective or interfering compounds from the eight absorbed compounds (8ACs), identify the primary ACs that represent the multifunctional therapeutic effects of Zhiqiao (Fructus Aurantii Submaturus) and Houpo (Cortex Magnoliae Officinalis) (FM), along with elucidating their underlying mechanisms.

METHODS: Key multifunctional ACs were screened through ex vivo-to-in vitro extrapolation (ex vivo dose = serum concentration) and validated in vivo, with efficacy assessed via contribution (dose = FM content). Functional magnetic resonance imaging analyzed brain regions’s blood oxygen level-dependent (BOLD) changes, and the molecular mechanisms were analyzed by transcriptome of the dentate gyrus (DG).

RESULTS: The results showed that representative 2ACs (Nobiletin + Magnolol) and 3ACs (Nobiletin + Magnolol + Meranzin hydrate) screened on ex vivo experiment by the criteria of contribution ranking contributed 80.72% -126.74% of the antidepressant and prokinetic effects of the FM (improvement of depressive-like behaviours, gastrointestinal disorder, monoamine neurotransmitters, ghrelin, endocrine hormones, pro-inflammatory factors, oxidative stress indicators). In addition, 3ACs demonstrated superiority over 2ACs in improving depression and levels of multiple stress mediators. Zhiqiao (Fructus Aurantii Submaturus) (FRA) reduced acute stress-induced hyperactivation of the cingulate cortex, thalamus, hypothalamus, and entorhinal cortex and elevated BOLD signaling in the insular cortex, temporal association cortex. Furthermore, FRA upregulated pathways of neurotransmitter receptor activity and serotonergic synaptic function and downregulated inflammation-related pathways at the genetic level.

CONCLUSION: 2ACs and 3ACs closely reflected FM’s multifunctional effect in antidepressant and prokinetic. FRA restores stress-impaired neural connectivity in functional brain regions and improves synaptic plasticity and neurogenesis at the genetic level.

Key words： Zhiqiao (Fructus Aurantii Submaturus); Houpo (Cortex Magnoliae Officinalis); multifunctional absorbed compounds; nobiletin; magnolol; meranzin hydrate

Cite this article

Runze ZHOU , Chendong XU , Haotian QIAN , Xi HUANG . Ex vivo to in vivo extrapolation of primary absorbed compounds as multifunctional proxies of Zhiqiao (Fructus Aurantii Submaturus)-Houpo (Cortex Magnoliae Officinalis) herb pair[J]. Journal of Traditional Chinese Medicine, 2026 , 46(1) : 51 -61 . DOI: 10.19852/j.cnki.jtcm.2026.01.005

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