1. Synergistic effects of citicoline and silymarin nanomicelles in restraint stress-exposed mice.
- Author
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Shayan E, Maheri F, Aflaki F, Mousavi SE, Zarrindast MR, Fakhraei N, Rezayat Sorkhabadi SM, and Shushtarian SM
- Subjects
- Mice, Animals, Brain-Derived Neurotrophic Factor metabolism, Cytidine Diphosphate Choline metabolism, Cytidine Diphosphate Choline pharmacology, Tumor Necrosis Factor-alpha metabolism, Hippocampus metabolism, Body Weight, Depression metabolism, Antidepressive Agents pharmacology, Silymarin pharmacology, Silymarin metabolism
- Abstract
This study evaluated the effects of citicoline and silymarin nanomicelles (SMnm) in repeated restraint stress (RRS)., Method: Mice were exposed to RRS for four consecutive days, 2 hrs. daily. On day 5 of the study, SMnm (25 and 50 mg/kg, i.p.) and citicoline (25 and 75 mg/kg), and a combination of them (25 mg/kg, i.p.) were initiated. On day 18, anxiety-like behavior, behavioral despair, and exploratory behavior were evaluated. The prefrontal cortex (PFC) and the hippocampus were dissected measuring brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and tumor necrosis factor-alpha (TNF-α) through Western Blot and ELISA, respectively., Results: In RR-exposed mice, anxiety-like behavior in the elevated plus maze (EPM) was enhanced by reductions in open arm time (OAT%) P < 0.001, and open arm entry (OAE%) P < 0.001. In the forced swimming test (FST), the immobility increased P < 0.001 while the swimming and climbing reduced P < 0.001. In the open field test (OFT), general motor activity was raised P < 0.05. Further, body weights reduced P < 0.001, and tissue BDNF and pCREB expressions decreased P < 0.001 while TNF-α increased P < 0.001. Conversely, SMnm, citicoline and their combination could reduce anxiety-like behavior P < 0.001. The combination group reduced the depressive-like behaviors P < 0.001. Moreover, body weights were restored P < 0.001. Besides, BDNF and pCREB expressions increased while TNF-α reduced, P < 0.001., Conclusion: The combination synergistically improved emotion-like behaviors, alleviating the inflammation and upregulating the hippocampal BDNF-mediated CREB signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare no competing financial and non-financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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