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Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1β pathway.
- Source :
-
Phytomedicine : international journal of phytotherapy and phytopharmacology [Phytomedicine] 2024 Sep; Vol. 132, pp. 155847. Date of Electronic Publication: 2024 Jul 03. - Publication Year :
- 2024
-
Abstract
- Background: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored.<br />Purpose: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL.<br />Methods: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments.<br />Results: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1β pathway and increased proinflammatory IL1β in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1β pathway.<br />Conclusions: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1β pathway, specifically by targeting AKK and tryptophan metabolites.<br />Competing Interests: Declaration of competing interest The authors have declared no conflict of interest.<br /> (Copyright © 2024 Elsevier GmbH. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Mice, Inbred C57BL
Caspase 1 metabolism
Fecal Microbiota Transplantation
Verrucomicrobia
Plant Extracts pharmacology
Signal Transduction drug effects
Dysbiosis drug therapy
Dysbiosis microbiology
Disease Models, Animal
Hypericum chemistry
Gastrointestinal Microbiome drug effects
Depression drug therapy
Tryptophan metabolism
Tryptophan pharmacology
NF-kappa B metabolism
Interleukin-1beta metabolism
Antidepressive Agents pharmacology
Akkermansia
Subjects
Details
- Language :
- English
- ISSN :
- 1618-095X
- Volume :
- 132
- Database :
- MEDLINE
- Journal :
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38996505
- Full Text :
- https://doi.org/10.1016/j.phymed.2024.155847