Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation
BackgroundAlthough our team has demonstrated the antidepressant effect of Gardeniae Fructus oil (OGF) in the early stages, the mechanism of whether OGF works by regulating the gut microbiota is not clear. This study aims to elucidate OGF’s gut-brain axis mechanism in depression.MethodsChronic unpred...
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Frontiers Media S.A.
2025-08-01
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| author | Man Han Man Han Man Han Yujing Zhou Yujing Zhou Yujing Zhou Xinyu Gao Xinyu Gao Xinyu Gao Xixi Cheng Xixi Cheng Xixi Cheng Ling Deng Ling Deng Ling Deng Shilin Ji Shilin Ji Shilin Ji Zhengheng Li Zhengheng Li Zhengheng Li Yu Cai Yu Cai Yu Cai Chunchao Yan Chunchao Yan Chunchao Yan Yunzhong Chen Yunzhong Chen Yunzhong Chen |
| author_facet | Man Han Man Han Man Han Yujing Zhou Yujing Zhou Yujing Zhou Xinyu Gao Xinyu Gao Xinyu Gao Xixi Cheng Xixi Cheng Xixi Cheng Ling Deng Ling Deng Ling Deng Shilin Ji Shilin Ji Shilin Ji Zhengheng Li Zhengheng Li Zhengheng Li Yu Cai Yu Cai Yu Cai Chunchao Yan Chunchao Yan Chunchao Yan Yunzhong Chen Yunzhong Chen Yunzhong Chen |
| author_sort | Man Han |
| collection | DOAJ |
| description | BackgroundAlthough our team has demonstrated the antidepressant effect of Gardeniae Fructus oil (OGF) in the early stages, the mechanism of whether OGF works by regulating the gut microbiota is not clear. This study aims to elucidate OGF’s gut-brain axis mechanism in depression.MethodsChronic unpredictable mild stress (CUMS) was used to establish a depressed mouse model, and the depression-like behavior of mice was observed by behavioral tests after antibiotic pretreatment and fecal microbiota transplantation (FMT). HE staining was used to observe the pathological changes in the hippocampus and colon; ELISA was used to detect the content of neurotransmitters and pro-inflammatory factors; Western blot was used to detect the expression of colonic tight junction proteins. The signaling pathways regulating the antidepressant properties of OGF were obtained by transcriptome sequencing analysis and validated at the protein level.ResultsCompared with the CON group, mice in the CUMS group showed significant depressive-like behavior, pathological damage to the hippocampus and colon tissues, significant decrease in levels of 5-HT, DA, and BDNF in the hippocampus, significant increase in levels of IL-1β, IL-6, TNF-α, DAO, and LPS in serum, significant decrease in colonic tight junction protein expression, and significant increase in protein expression of TLR4, p-NF-κB, NLRP3, ASC, and IL-1β in the hippocampus (P < 0.01); Compared with the CUMS group, the FMT group could effectively improve the above situation (P < 0.05, P < 0.01), whose therapeutic effect was second only to the OGF group (P < 0.01), while ABX + OGF group did not show obvious therapeutic effect.ConclusionOGF might exert antidepressant effects by modulating gut microbiota and mediating the hippocampal TLR4/NF-κB/NLRP3 pathway. |
| format | Article |
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| issn | 1663-9812 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-cc47d9713f1b4dc3a83b42eaaf6058c02025-08-01T05:32:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.16358971635897Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantationMan Han0Man Han1Man Han2Yujing Zhou3Yujing Zhou4Yujing Zhou5Xinyu Gao6Xinyu Gao7Xinyu Gao8Xixi Cheng9Xixi Cheng10Xixi Cheng11Ling Deng12Ling Deng13Ling Deng14Shilin Ji15Shilin Ji16Shilin Ji17Zhengheng Li18Zhengheng Li19Zhengheng Li20Yu Cai21Yu Cai22Yu Cai23Chunchao Yan24Chunchao Yan25Chunchao Yan26Yunzhong Chen27Yunzhong Chen28Yunzhong Chen29Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaFaculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Provincial Research Center for TCM Health Food Engineering, Hubei University of Chinese Medicine, Wuhan, ChinaHubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, ChinaBackgroundAlthough our team has demonstrated the antidepressant effect of Gardeniae Fructus oil (OGF) in the early stages, the mechanism of whether OGF works by regulating the gut microbiota is not clear. This study aims to elucidate OGF’s gut-brain axis mechanism in depression.MethodsChronic unpredictable mild stress (CUMS) was used to establish a depressed mouse model, and the depression-like behavior of mice was observed by behavioral tests after antibiotic pretreatment and fecal microbiota transplantation (FMT). HE staining was used to observe the pathological changes in the hippocampus and colon; ELISA was used to detect the content of neurotransmitters and pro-inflammatory factors; Western blot was used to detect the expression of colonic tight junction proteins. The signaling pathways regulating the antidepressant properties of OGF were obtained by transcriptome sequencing analysis and validated at the protein level.ResultsCompared with the CON group, mice in the CUMS group showed significant depressive-like behavior, pathological damage to the hippocampus and colon tissues, significant decrease in levels of 5-HT, DA, and BDNF in the hippocampus, significant increase in levels of IL-1β, IL-6, TNF-α, DAO, and LPS in serum, significant decrease in colonic tight junction protein expression, and significant increase in protein expression of TLR4, p-NF-κB, NLRP3, ASC, and IL-1β in the hippocampus (P < 0.01); Compared with the CUMS group, the FMT group could effectively improve the above situation (P < 0.05, P < 0.01), whose therapeutic effect was second only to the OGF group (P < 0.01), while ABX + OGF group did not show obvious therapeutic effect.ConclusionOGF might exert antidepressant effects by modulating gut microbiota and mediating the hippocampal TLR4/NF-κB/NLRP3 pathway.https://www.frontiersin.org/articles/10.3389/fphar.2025.1635897/fullGardeniae Fructus oildepressionchronic unpredictable mild stressfecal microbiota transplantationtranscriptomicsgut-brain axis |
| spellingShingle | Man Han Man Han Man Han Yujing Zhou Yujing Zhou Yujing Zhou Xinyu Gao Xinyu Gao Xinyu Gao Xixi Cheng Xixi Cheng Xixi Cheng Ling Deng Ling Deng Ling Deng Shilin Ji Shilin Ji Shilin Ji Zhengheng Li Zhengheng Li Zhengheng Li Yu Cai Yu Cai Yu Cai Chunchao Yan Chunchao Yan Chunchao Yan Yunzhong Chen Yunzhong Chen Yunzhong Chen Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation Frontiers in Pharmacology Gardeniae Fructus oil depression chronic unpredictable mild stress fecal microbiota transplantation transcriptomics gut-brain axis |
| title | Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation |
| title_full | Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation |
| title_fullStr | Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation |
| title_full_unstemmed | Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation |
| title_short | Modulation of gut microbiota by Gardeniae Fructus oil exerts TLR4/NF-κB/NLRP3 pathway-mediated antidepressant effects based on transcriptomics and fecal transplantation |
| title_sort | modulation of gut microbiota by gardeniae fructus oil exerts tlr4 nf κb nlrp3 pathway mediated antidepressant effects based on transcriptomics and fecal transplantation |
| topic | Gardeniae Fructus oil depression chronic unpredictable mild stress fecal microbiota transplantation transcriptomics gut-brain axis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1635897/full |
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