Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats
Background: Salvianolic acids possess anti-inflammatory properties. This study investigated the therapeutic effect of salvianolic acids on chronic mild stress (CMS)-induced depressive-like behaviors in rats and the involvement of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD...
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Language: | English |
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IMR Press
2023-05-01
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Series: | Journal of Integrative Neuroscience |
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Online Access: | https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203060 |
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author | Fengya Zhen Lulu Yu Lan Wang Shuo Wang Wenting Lu Xueyi Wang Cuixia An |
author_facet | Fengya Zhen Lulu Yu Lan Wang Shuo Wang Wenting Lu Xueyi Wang Cuixia An |
author_sort | Fengya Zhen |
collection | DOAJ |
description | Background: Salvianolic acids possess anti-inflammatory properties. This study investigated the therapeutic effect of salvianolic acids on chronic mild stress (CMS)-induced depressive-like behaviors in rats and the involvement of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Methods: Eighty male Sprague-Dawley rats were randomly subjected to CMS or non-CMS protocol for 6 weeks. Starting 3 weeks after CMS exposure, the rats in each group were administered saline, fluoxetine (positive control), salvianolic acids, or salvianolic acids + fluoxetine daily for 3 weeks. The body weight change, sucrose preference, and immobility duration in forced swimming were examined before and after drug treatment. The rats were sacrificed at 3 weeks after drug treatment. Quantitative real-time PCR was performed to measure the mRNA levels of TLR4 and MyD88 in the prefrontal cortex and hippocampus of rats. Results: Compared with non-CMS rats, CMS rats had significantly reduced weight gains and sucrose preference, along with significantly increased immobility durations and elevated mRNA levels of TLR4 and MyD88 in both the prefrontal cortex and hippocampus. Treatment with fluoxetine and salvianolic acids, alone or in combination, facilitated weight gains, alleviated depressive-like behaviors, and reduced cerebral TLR4/MyD88 mRNA levels in CMS rats. Besides, fluoxetine and salvianolic acids additively suppressed TLR4/MyD88 mRNA expression in the prefrontal cortex of rats. Furthermore, TLR4 mRNA levels in both hippocampus and prefrontal cortex positively correlated with MyD88 mRNA expression, inflammatory cytokine secretion, and immobility duration but negatively correlated with sucrose preference. Conclusions: Thus, salvianolic acids alleviate depressive-like behaviors, possibly by suppressing TLR4/MyD88-mediated inflammatory signaling in the brain. |
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spelling | doaj.art-d3f560a381c14280bf5b9ac3a52386462023-06-01T01:59:17ZengIMR PressJournal of Integrative Neuroscience0219-63522023-05-012236010.31083/j.jin2203060S0219-6352(22)00469-7Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in RatsFengya Zhen0Lulu Yu1Lan Wang2Shuo Wang3Wenting Lu4Xueyi Wang5Cuixia An6Department of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaDepartment of Psychiatry, the First Hospital of Hebei Medical University, 050031 Shijiazhuang, Hebei, ChinaBackground: Salvianolic acids possess anti-inflammatory properties. This study investigated the therapeutic effect of salvianolic acids on chronic mild stress (CMS)-induced depressive-like behaviors in rats and the involvement of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Methods: Eighty male Sprague-Dawley rats were randomly subjected to CMS or non-CMS protocol for 6 weeks. Starting 3 weeks after CMS exposure, the rats in each group were administered saline, fluoxetine (positive control), salvianolic acids, or salvianolic acids + fluoxetine daily for 3 weeks. The body weight change, sucrose preference, and immobility duration in forced swimming were examined before and after drug treatment. The rats were sacrificed at 3 weeks after drug treatment. Quantitative real-time PCR was performed to measure the mRNA levels of TLR4 and MyD88 in the prefrontal cortex and hippocampus of rats. Results: Compared with non-CMS rats, CMS rats had significantly reduced weight gains and sucrose preference, along with significantly increased immobility durations and elevated mRNA levels of TLR4 and MyD88 in both the prefrontal cortex and hippocampus. Treatment with fluoxetine and salvianolic acids, alone or in combination, facilitated weight gains, alleviated depressive-like behaviors, and reduced cerebral TLR4/MyD88 mRNA levels in CMS rats. Besides, fluoxetine and salvianolic acids additively suppressed TLR4/MyD88 mRNA expression in the prefrontal cortex of rats. Furthermore, TLR4 mRNA levels in both hippocampus and prefrontal cortex positively correlated with MyD88 mRNA expression, inflammatory cytokine secretion, and immobility duration but negatively correlated with sucrose preference. Conclusions: Thus, salvianolic acids alleviate depressive-like behaviors, possibly by suppressing TLR4/MyD88-mediated inflammatory signaling in the brain.https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203060chronic mild stressdepressionsalvia miltiorrhizasalvianolic acidstoll-like receptor 4myeloid differentiation factor 88 |
spellingShingle | Fengya Zhen Lulu Yu Lan Wang Shuo Wang Wenting Lu Xueyi Wang Cuixia An Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats Journal of Integrative Neuroscience chronic mild stress depression salvia miltiorrhiza salvianolic acids toll-like receptor 4 myeloid differentiation factor 88 |
title | Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats |
title_full | Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats |
title_fullStr | Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats |
title_full_unstemmed | Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats |
title_short | Salvianolic Acids Alleviate Chronic Mild Stress-Induced Depressive-Like Behaviors in Rats |
title_sort | salvianolic acids alleviate chronic mild stress induced depressive like behaviors in rats |
topic | chronic mild stress depression salvia miltiorrhiza salvianolic acids toll-like receptor 4 myeloid differentiation factor 88 |
url | https://www.imrpress.com/journal/JIN/22/3/10.31083/j.jin2203060 |
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