Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling
Depression is a widespread mental disorder with extremely complex pathogenesis, and its effective treatment still requires to be solved. Juglanin (Jug) is a natural compound with anti-inflammatory, antioxidant and anti-tumor effects, but whether it shows neuroprotective effects for depression treatm...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Journal of Functional Foods |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464622003334 |
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| author | Yanrong Ren Shiwen Hu Hongzheng Pu Ying Zhou Mingzhu Jiang Yuanyuan Li Chaofang Deng Jie Gao Minxuan Xu Chenxu Ge |
| author_facet | Yanrong Ren Shiwen Hu Hongzheng Pu Ying Zhou Mingzhu Jiang Yuanyuan Li Chaofang Deng Jie Gao Minxuan Xu Chenxu Ge |
| author_sort | Yanrong Ren |
| collection | DOAJ |
| description | Depression is a widespread mental disorder with extremely complex pathogenesis, and its effective treatment still requires to be solved. Juglanin (Jug) is a natural compound with anti-inflammatory, antioxidant and anti-tumor effects, but whether it shows neuroprotective effects for depression treatment is largely unknown. In the present study, the chronic unpredictable mild stress (CUMS) mouse model and lipopolysaccharide (LPS)-stimulated cells were constructed to explore the regulatory potential of Jug on depression in vivo and in vitro, respectively. Numerous behavioral tests at first revealed that Jug supplementation significantly ameliorated anxiety/depression-like behavior and cognitive impairment in CUMS mice. CUMS-induced abnormal releases of stress-related markers in serum or hippocampus were strongly reversed in mice co-treated with Jug. Furthermore, neuronal death in hippocampus triggered by CUMS was highly abolished by Jug administration through increasing protein kinase B (AKT) activation and Caspase-3 blockage. We also found that glial activation due to CUMS was evidently ameliorated by Jug, as evidenced by the decreased CD11b and glial fibrillary acidic protein (GFAP) expression. Consistently, hippocampal neuroinflammation caused by CUMS was also considerably mitigated upon Jug consumption by prohibiting nuclear factor-kappa B (NF-κB) signaling. These neuroprotective and anti-inflammatory effects of Jug were confirmed in LPS-stimulated mouse hippocampal neurons and microglial cells via the same mechanisms. Importantly, we found that Jug treatment remarkably rescued AMP-activated protein kinase (AMPK) phosphorylation in hippocampus of CUMS mice, which was also observed in neurons and microglial cells under inflammatory conditions. Surprisingly, our in vitro experiments showed that AMPK deletion almost diminished the function of Jug to improve neuron survival and restrain neuroinflammation in LPS-exposed neurons and microglial cells, respectively, which were accompanied by AKT blockage and NF-κB activation recovery. These data suggested that the neuroprotective and anti-inflammatory capacity of Jug was AMPK-dependent. Collectively, we provided evidence that Jug might be a novel therapeutic strategy for depression treatment by improving AMPK activation. |
| first_indexed | 2024-04-13T14:48:06Z |
| format | Article |
| id | doaj.art-7e71e38688ea4d2a9f39e0a618656508 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-04-13T14:48:06Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-7e71e38688ea4d2a9f39e0a6186565082022-12-22T02:42:42ZengElsevierJournal of Functional Foods1756-46462022-11-0198105263Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signalingYanrong Ren0Shiwen Hu1Hongzheng Pu2Ying Zhou3Mingzhu Jiang4Yuanyuan Li5Chaofang Deng6Jie Gao7Minxuan Xu8Chenxu Ge9Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China; Corresponding authors at: Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China.Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR ChinaDepartment of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China; Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; Corresponding authors at: Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China.Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China; College of Modern Health Industry, Chongqing University of Education, Chongqing 400067, PR China; Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; Corresponding authors at: Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China.Depression is a widespread mental disorder with extremely complex pathogenesis, and its effective treatment still requires to be solved. Juglanin (Jug) is a natural compound with anti-inflammatory, antioxidant and anti-tumor effects, but whether it shows neuroprotective effects for depression treatment is largely unknown. In the present study, the chronic unpredictable mild stress (CUMS) mouse model and lipopolysaccharide (LPS)-stimulated cells were constructed to explore the regulatory potential of Jug on depression in vivo and in vitro, respectively. Numerous behavioral tests at first revealed that Jug supplementation significantly ameliorated anxiety/depression-like behavior and cognitive impairment in CUMS mice. CUMS-induced abnormal releases of stress-related markers in serum or hippocampus were strongly reversed in mice co-treated with Jug. Furthermore, neuronal death in hippocampus triggered by CUMS was highly abolished by Jug administration through increasing protein kinase B (AKT) activation and Caspase-3 blockage. We also found that glial activation due to CUMS was evidently ameliorated by Jug, as evidenced by the decreased CD11b and glial fibrillary acidic protein (GFAP) expression. Consistently, hippocampal neuroinflammation caused by CUMS was also considerably mitigated upon Jug consumption by prohibiting nuclear factor-kappa B (NF-κB) signaling. These neuroprotective and anti-inflammatory effects of Jug were confirmed in LPS-stimulated mouse hippocampal neurons and microglial cells via the same mechanisms. Importantly, we found that Jug treatment remarkably rescued AMP-activated protein kinase (AMPK) phosphorylation in hippocampus of CUMS mice, which was also observed in neurons and microglial cells under inflammatory conditions. Surprisingly, our in vitro experiments showed that AMPK deletion almost diminished the function of Jug to improve neuron survival and restrain neuroinflammation in LPS-exposed neurons and microglial cells, respectively, which were accompanied by AKT blockage and NF-κB activation recovery. These data suggested that the neuroprotective and anti-inflammatory capacity of Jug was AMPK-dependent. Collectively, we provided evidence that Jug might be a novel therapeutic strategy for depression treatment by improving AMPK activation.http://www.sciencedirect.com/science/article/pii/S1756464622003334DepressionCUMSNeuron survivalNeuroinflammationAMPK |
| spellingShingle | Yanrong Ren Shiwen Hu Hongzheng Pu Ying Zhou Mingzhu Jiang Yuanyuan Li Chaofang Deng Jie Gao Minxuan Xu Chenxu Ge Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling Journal of Functional Foods Depression CUMS Neuron survival Neuroinflammation AMPK |
| title | Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling |
| title_full | Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling |
| title_fullStr | Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling |
| title_full_unstemmed | Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling |
| title_short | Juglanin ameliorates depression-like behavior in chronic unpredictable mild stress-induced mice by improving AMPK signaling |
| title_sort | juglanin ameliorates depression like behavior in chronic unpredictable mild stress induced mice by improving ampk signaling |
| topic | Depression CUMS Neuron survival Neuroinflammation AMPK |
| url | http://www.sciencedirect.com/science/article/pii/S1756464622003334 |
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