ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1642515
This article is part of the Research TopicExploring Untapped Potential: Innovations in Drug RepurposingView all 15 articles
Hemerocallis citrina Baroni leaf total phenol alleviates depressive-like behaviors via modulating "microbiota-gut-brain" axis in chronic unpredictable mild stress -induced rats
Provisionally accepted
- 1Lanzhou University, Lanzhou, China
- 2Lanzhou Foci Pharmaceutical Co., Ltd., Lanzhou, China
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Depression is closely associated with dysfunction of the microbiota-gut-brain axis (MGBA). Total phenol from Hemerocallis citrina leaves (HLTP) exhibits antidepressant potential, but its role in relieving depression by regulating MGBA remains uninvestigated. In this study, the chronic unpredictable mild stress (CUMS) method was used to establish a rat model of depression to investigate the ameliorative effects of HLTP on depression. Behavioral and pathological results showed HLTP improved weight loss, increased sucrose preference, reduced forced swimming immobility time, novel-suppressed feeding latency, open field movement trajectory, and alleviated hippocampal CA1 neuronal damage in CUMS-depressed rats. At 10, 20, and 40 mg/kg, HLTP increased dopamine (DA), noradrenaline (NE), 5-hydroxytryptamine (5-HT), interleukin-10 (IL-10), brain-derived neurotrophic factor (BDNF), and cAMP response element-binding protein (CREB) in the brain. It also decreased the inflammatory factor (TNF-α and IL-1β) in the brain, as well as corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in serum and brain. HLTP modulated gut microbiota diversity and reversed CUMS-induced alterations in 15 bacterial taxa, including Alloprevotella and Monoglobus. Additionally, HLTP reversed 63 CUMS-induced abnormal serum metabolites, primarily affecting tryptophan metabolism, niacin and nicotinamide metabolism, and porphyrin metabolism. Significant correlations were observed among gut microbial composition, serum metabolite levels, biochemical indices, and behavioral outcomes. HLTP exerts antidepressant effects in CUMS-induced rats by modulating the MGBA. It enhances metabolic function, reduces neuroinflammatory damage, restores neurotrophic factor levels, suppresses hyperactivity of the hypothalamic-pituitary-adrenal axis, and corrects monoamine neurotransmitter deficiencies, collectively contributing to the attenuation of depression-related symptoms.
Keywords: Hemerocallis citrina Baroni leaf, Total phenols, Chronic unpredictable mild stress, Microbiota-gut-brain axis, antidepressant activity, Gut Microbiota, non-targeted metabolomics
Received: 06 Jun 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Wang, Jia, Zhao, Shao, Zhang, Chen, Qian and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fangdi Hu, Lanzhou University, Lanzhou, China
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