Neohesperidin Improves Depressive-Like Behavior Induced by Chronic Unpredictable Mild Stress in Mice
Depression is a common and complex neuropsychiatric disorder affecting people of all ages worldwide, associated with high rates of relapse and disability. Neohesperidin (NEO) is a dietary flavonoid with applications in therapeutics; however, its effects on depressive-like behavior remain unknown. He...
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| Veröffentlicht in: | Neurochemical research 2025-02, Vol.50 (1), p.69, Article 69 |
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| creator | Luo, Li Liu, Wenna Dong, Leipeng Wang, Saiying Wang, Qinhui Jiang, Yuting Zhao, Minggao Liu, An Yang, Le |
| description | Depression is a common and complex neuropsychiatric disorder affecting people of all ages worldwide, associated with high rates of relapse and disability. Neohesperidin (NEO) is a dietary flavonoid with applications in therapeutics; however, its effects on depressive-like behavior remain unknown. Here, we evaluated the effects of NEO on depressive-like behavior induced by chronic and unpredictable mild stress (CUMS). NEO (25, 50, and 100 mg kg
–1
) treatment for two weeks dose-dependently improved CUMS-induced depressive-like behavior measured by the sucrose preference, open field, forced swimming, and tail suspension tests. Moreover, NEO effectively blocked the decrease of superoxide dismutase, catalase, and glutathione peroxidase activity and the increase of malondialdehyde levels, which are markers of oxidative stress. In addition, NEO inhibited microglial activation and the production of proinflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in the hippocampus and prefrontal cortex. Molecular docking and dynamic simulations showed that NEO has good affinity for NOD-like receptor protein 3 (NLRP3), suggesting that NEO may play an antidepressant role by regulating the NLRP3 signaling pathway. Western blotting results further revealed that the increased expression level of NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) in CUMS mice was significantly reversed by NEO treatment. These results suggest that NEO is a candidate for treating depression and should be considered for further clinical development. |
| doi_str_mv | 10.1007/s11064-024-04323-5 |
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–1
) treatment for two weeks dose-dependently improved CUMS-induced depressive-like behavior measured by the sucrose preference, open field, forced swimming, and tail suspension tests. Moreover, NEO effectively blocked the decrease of superoxide dismutase, catalase, and glutathione peroxidase activity and the increase of malondialdehyde levels, which are markers of oxidative stress. In addition, NEO inhibited microglial activation and the production of proinflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in the hippocampus and prefrontal cortex. Molecular docking and dynamic simulations showed that NEO has good affinity for NOD-like receptor protein 3 (NLRP3), suggesting that NEO may play an antidepressant role by regulating the NLRP3 signaling pathway. Western blotting results further revealed that the increased expression level of NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) in CUMS mice was significantly reversed by NEO treatment. These results suggest that NEO is a candidate for treating depression and should be considered for further clinical development.</description><identifier>ISSN: 0364-3190</identifier><identifier>ISSN: 1573-6903</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-024-04323-5</identifier><identifier>PMID: 39751909</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antidepressants ; Antidepressive Agents - pharmacology ; Antidepressive Agents - therapeutic use ; Behavior, Animal - drug effects ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Caspase-1 ; Catalase ; Cell Biology ; Depression - drug therapy ; Depression - metabolism ; Flavonoids ; Glutathione ; Glutathione peroxidase ; Hesperidin - analogs & derivatives ; Hesperidin - pharmacology ; Hesperidin - therapeutic use ; Hippocampus - drug effects ; Hippocampus - metabolism ; Inflammasomes ; Male ; Mental depression ; Mental disorders ; Mice ; Molecular docking ; Molecular Docking Simulation ; Neohesperidin dihydrochalcone ; Neurochemistry ; Neurology ; Neurosciences ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; Open-field behavior ; Oxidative stress ; Oxidative Stress - drug effects ; Peroxidase ; Prefrontal cortex ; Prefrontal Cortex - drug effects ; Prefrontal Cortex - metabolism ; Signal transduction ; Stress, Psychological - drug therapy ; Stress, Psychological - metabolism ; Stress, Psychological - psychology ; Sucrose ; Superoxide dismutase ; Swimming behavior ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Western blotting</subject><ispartof>Neurochemical research, 2025-02, Vol.50 (1), p.69, Article 69</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>Copyright Springer Nature B.V. Feb 2025</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1715-566db7ca2bf3298982205c59d7b5689fbfcc7ad3119836b5fb0ba6c409b1511f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11064-024-04323-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11064-024-04323-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39751909$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luo, Li</creatorcontrib><creatorcontrib>Liu, Wenna</creatorcontrib><creatorcontrib>Dong, Leipeng</creatorcontrib><creatorcontrib>Wang, Saiying</creatorcontrib><creatorcontrib>Wang, Qinhui</creatorcontrib><creatorcontrib>Jiang, Yuting</creatorcontrib><creatorcontrib>Zhao, Minggao</creatorcontrib><creatorcontrib>Liu, An</creatorcontrib><creatorcontrib>Yang, Le</creatorcontrib><title>Neohesperidin Improves Depressive-Like Behavior Induced by Chronic Unpredictable Mild Stress in Mice</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><addtitle>Neurochem Res</addtitle><description>Depression is a common and complex neuropsychiatric disorder affecting people of all ages worldwide, associated with high rates of relapse and disability. Neohesperidin (NEO) is a dietary flavonoid with applications in therapeutics; however, its effects on depressive-like behavior remain unknown. Here, we evaluated the effects of NEO on depressive-like behavior induced by chronic and unpredictable mild stress (CUMS). NEO (25, 50, and 100 mg kg
–1
) treatment for two weeks dose-dependently improved CUMS-induced depressive-like behavior measured by the sucrose preference, open field, forced swimming, and tail suspension tests. Moreover, NEO effectively blocked the decrease of superoxide dismutase, catalase, and glutathione peroxidase activity and the increase of malondialdehyde levels, which are markers of oxidative stress. In addition, NEO inhibited microglial activation and the production of proinflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in the hippocampus and prefrontal cortex. Molecular docking and dynamic simulations showed that NEO has good affinity for NOD-like receptor protein 3 (NLRP3), suggesting that NEO may play an antidepressant role by regulating the NLRP3 signaling pathway. Western blotting results further revealed that the increased expression level of NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) in CUMS mice was significantly reversed by NEO treatment. These results suggest that NEO is a candidate for treating depression and should be considered for further clinical development.</description><subject>Animals</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - pharmacology</subject><subject>Antidepressive Agents - therapeutic use</subject><subject>Behavior, Animal - drug effects</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Caspase-1</subject><subject>Catalase</subject><subject>Cell Biology</subject><subject>Depression - drug therapy</subject><subject>Depression - metabolism</subject><subject>Flavonoids</subject><subject>Glutathione</subject><subject>Glutathione peroxidase</subject><subject>Hesperidin - analogs & derivatives</subject><subject>Hesperidin - pharmacology</subject><subject>Hesperidin - therapeutic use</subject><subject>Hippocampus - drug effects</subject><subject>Hippocampus - metabolism</subject><subject>Inflammasomes</subject><subject>Male</subject><subject>Mental depression</subject><subject>Mental disorders</subject><subject>Mice</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Neohesperidin dihydrochalcone</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>Open-field behavior</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Peroxidase</subject><subject>Prefrontal cortex</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Signal transduction</subject><subject>Stress, Psychological - drug therapy</subject><subject>Stress, Psychological - metabolism</subject><subject>Stress, Psychological - psychology</subject><subject>Sucrose</subject><subject>Superoxide dismutase</subject><subject>Swimming behavior</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Western blotting</subject><issn>0364-3190</issn><issn>1573-6903</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtPAyEUhYnR2Fr9Ay4MiRs3ozwKU5ZaX02qLtQ1GeCORaczFTpN-u9Fp2riwsUNyb3fOcA9CB1SckoJyc8ipUQOM8JSDTnjmdhCfSpynklF-DbqE57GnCrSQ3sxvhKSZIzuoh5XuUht1UfuHpoZxAUE73yNJ_NFaFYQ8SUsAsToV5BN_RvgC5gVK98EPKlda8Fhs8bjWWhqb_FznVjn7bIwFeA7Xzn8uPxU4-R45y3so52yqCIcbM4Ber6-ehrfZtOHm8n4fJpZmlORCSmdyW3BTMmZGqkRY0RYoVxuhByp0pTW5oXjlKoRl0aUhphC2iFRhgpKSz5AJ51v-sR7C3Gp5z5aqKqihqaNmieMUZZLmdDjP-hr04Y6va6j1FCmjQ4Q6ygbmhgDlHoR_LwIa02J_sxAdxnolIH-ykCLJDraWLdmDu5H8r30BPAOiGlUv0D4vfsf2w9aYJDZ</recordid><startdate>20250201</startdate><enddate>20250201</enddate><creator>Luo, Li</creator><creator>Liu, Wenna</creator><creator>Dong, Leipeng</creator><creator>Wang, Saiying</creator><creator>Wang, Qinhui</creator><creator>Jiang, Yuting</creator><creator>Zhao, Minggao</creator><creator>Liu, An</creator><creator>Yang, Le</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20250201</creationdate><title>Neohesperidin Improves Depressive-Like Behavior Induced by Chronic Unpredictable Mild Stress in Mice</title><author>Luo, Li ; Liu, Wenna ; Dong, Leipeng ; Wang, Saiying ; Wang, Qinhui ; Jiang, Yuting ; Zhao, Minggao ; Liu, An ; Yang, Le</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1715-566db7ca2bf3298982205c59d7b5689fbfcc7ad3119836b5fb0ba6c409b1511f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Animals</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - pharmacology</topic><topic>Antidepressive Agents - therapeutic use</topic><topic>Behavior, Animal - drug effects</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Caspase-1</topic><topic>Catalase</topic><topic>Cell Biology</topic><topic>Depression - drug therapy</topic><topic>Depression - metabolism</topic><topic>Flavonoids</topic><topic>Glutathione</topic><topic>Glutathione peroxidase</topic><topic>Hesperidin - analogs & derivatives</topic><topic>Hesperidin - pharmacology</topic><topic>Hesperidin - therapeutic use</topic><topic>Hippocampus - drug effects</topic><topic>Hippocampus - metabolism</topic><topic>Inflammasomes</topic><topic>Male</topic><topic>Mental depression</topic><topic>Mental disorders</topic><topic>Mice</topic><topic>Molecular docking</topic><topic>Molecular Docking Simulation</topic><topic>Neohesperidin dihydrochalcone</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>Open-field behavior</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Peroxidase</topic><topic>Prefrontal cortex</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Signal transduction</topic><topic>Stress, Psychological - drug therapy</topic><topic>Stress, Psychological - metabolism</topic><topic>Stress, Psychological - psychology</topic><topic>Sucrose</topic><topic>Superoxide dismutase</topic><topic>Swimming behavior</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Luo, Li</creatorcontrib><creatorcontrib>Liu, Wenna</creatorcontrib><creatorcontrib>Dong, Leipeng</creatorcontrib><creatorcontrib>Wang, Saiying</creatorcontrib><creatorcontrib>Wang, Qinhui</creatorcontrib><creatorcontrib>Jiang, Yuting</creatorcontrib><creatorcontrib>Zhao, Minggao</creatorcontrib><creatorcontrib>Liu, An</creatorcontrib><creatorcontrib>Yang, Le</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Luo, Li</au><au>Liu, Wenna</au><au>Dong, Leipeng</au><au>Wang, Saiying</au><au>Wang, Qinhui</au><au>Jiang, Yuting</au><au>Zhao, Minggao</au><au>Liu, An</au><au>Yang, Le</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neohesperidin Improves Depressive-Like Behavior Induced by Chronic Unpredictable Mild Stress in Mice</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2025-02-01</date><risdate>2025</risdate><volume>50</volume><issue>1</issue><spage>69</spage><pages>69-</pages><artnum>69</artnum><issn>0364-3190</issn><issn>1573-6903</issn><eissn>1573-6903</eissn><abstract>Depression is a common and complex neuropsychiatric disorder affecting people of all ages worldwide, associated with high rates of relapse and disability. Neohesperidin (NEO) is a dietary flavonoid with applications in therapeutics; however, its effects on depressive-like behavior remain unknown. Here, we evaluated the effects of NEO on depressive-like behavior induced by chronic and unpredictable mild stress (CUMS). NEO (25, 50, and 100 mg kg
–1
) treatment for two weeks dose-dependently improved CUMS-induced depressive-like behavior measured by the sucrose preference, open field, forced swimming, and tail suspension tests. Moreover, NEO effectively blocked the decrease of superoxide dismutase, catalase, and glutathione peroxidase activity and the increase of malondialdehyde levels, which are markers of oxidative stress. In addition, NEO inhibited microglial activation and the production of proinflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α) in the hippocampus and prefrontal cortex. Molecular docking and dynamic simulations showed that NEO has good affinity for NOD-like receptor protein 3 (NLRP3), suggesting that NEO may play an antidepressant role by regulating the NLRP3 signaling pathway. Western blotting results further revealed that the increased expression level of NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) in CUMS mice was significantly reversed by NEO treatment. These results suggest that NEO is a candidate for treating depression and should be considered for further clinical development.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>39751909</pmid><doi>10.1007/s11064-024-04323-5</doi></addata></record> |
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| subjects | Animals Antidepressants Antidepressive Agents - pharmacology Antidepressive Agents - therapeutic use Behavior, Animal - drug effects Biochemistry Biomedical and Life Sciences Biomedicine Caspase-1 Catalase Cell Biology Depression - drug therapy Depression - metabolism Flavonoids Glutathione Glutathione peroxidase Hesperidin - analogs & derivatives Hesperidin - pharmacology Hesperidin - therapeutic use Hippocampus - drug effects Hippocampus - metabolism Inflammasomes Male Mental depression Mental disorders Mice Molecular docking Molecular Docking Simulation Neohesperidin dihydrochalcone Neurochemistry Neurology Neurosciences NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Open-field behavior Oxidative stress Oxidative Stress - drug effects Peroxidase Prefrontal cortex Prefrontal Cortex - drug effects Prefrontal Cortex - metabolism Signal transduction Stress, Psychological - drug therapy Stress, Psychological - metabolism Stress, Psychological - psychology Sucrose Superoxide dismutase Swimming behavior Tumor necrosis factor-TNF Tumor necrosis factor-α Western blotting |
| title | Neohesperidin Improves Depressive-Like Behavior Induced by Chronic Unpredictable Mild Stress in Mice |
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