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Dl-3-n-Butylphthalide improves lipopolysaccharide-induced depressive-like behavior in rats: involvement of Nrf2 and NF-κB pathways.

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Title: Dl-3-n-Butylphthalide improves lipopolysaccharide-induced depressive-like behavior in rats: involvement of Nrf2 and NF-κB pathways.
Authors: Yang, Mengqi, Dang, Ruili, Xu, Pengfei, Guo, Yujin, Han, Wenxiu, Liao, Dehua, Jiang, Pei
Source: Psychopharmacology. Sep2018, Vol. 235 Issue 9, p2573-2585. 13p. 1 Diagram, 1 Chart, 5 Graphs.
Subjects: Small molecules, Celery, Seeds, Lipopolysaccharides, Animal models of mental depression, Rat behavior, Therapeutics
Abstract: Rationale and objectives: Dl-3-n-Butylphthalide (NBP), a small molecule compound extracted from the seeds of Apium graveolens, possesses a large range of biological effects. Here, we attempted to explore the therapeutic effects of NBP on lipopolysaccharide (LPS)-induced major depressive disorder (MDD) and gain further insight into the underlying mechanisms of the antidepressant effects of NBP.Methods: We evaluated the effect of NBP against LPS-induced behavioral changes in rats. We also examined the inflammation, oxidative stress, and apoptosis markers and analyzed the Nrf2 and NF-κB pathways in the hippocampus of rats following repeated peripheral immune challenge by LPS for 2 weeks (500 μg/kg every other day).Results: Our results indicated that repeated LPS administration induced the rats to a depressive-like state and activated inflammatory response, oxidative stress, and apoptosis reactions in the hippocampus. NBP treatment attenuated the LPS-induced abnormal behavior and ameliorated pathogenic processes in rats with MDD. NBP reduced the inflammatory response with inhibited expression of pro-inflammatory cytokines including IL-1β and IL-6 and downregulated the NF-κB signal pathway. Concurrent with the anti-inflammation action, NBP reduced LPS-induced oxidative reactions in the hippocampus and enhanced Nrf2-targeted signals, as evidenced by increased transcription of antioxidant enzymes and decreased malondialdehyde (MDA) production. In addition, NBP inhibited LPS-induced neuronal apoptosis in the rat brain, as evidenced by decreased apoptosis marker Caspase-3 production and TUNEL assay.Conclusions: These results provide more insight into pathogenesis of MDD and firstly demonstrated the potential antidepressant actions of NBP. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Dl-3-n-Butylphthalide improves lipopolysaccharide-induced depressive-like behavior in rats: involvement of Nrf2 and NF-κB pathways.
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  Data: <searchLink fieldCode="AR" term="%22Yang%2C+Mengqi%22">Yang, Mengqi</searchLink><br /><searchLink fieldCode="AR" term="%22Dang%2C+Ruili%22">Dang, Ruili</searchLink><br /><searchLink fieldCode="AR" term="%22Xu%2C+Pengfei%22">Xu, Pengfei</searchLink><br /><searchLink fieldCode="AR" term="%22Guo%2C+Yujin%22">Guo, Yujin</searchLink><br /><searchLink fieldCode="AR" term="%22Han%2C+Wenxiu%22">Han, Wenxiu</searchLink><br /><searchLink fieldCode="AR" term="%22Liao%2C+Dehua%22">Liao, Dehua</searchLink><br /><searchLink fieldCode="AR" term="%22Jiang%2C+Pei%22">Jiang, Pei</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Sep2018, Vol. 235 Issue 9, p2573-2585. 13p. 1 Diagram, 1 Chart, 5 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Small+molecules%22">Small molecules</searchLink><br /><searchLink fieldCode="DE" term="%22Celery%22">Celery</searchLink><br /><searchLink fieldCode="DE" term="%22Seeds%22">Seeds</searchLink><br /><searchLink fieldCode="DE" term="%22Lipopolysaccharides%22">Lipopolysaccharides</searchLink><br /><searchLink fieldCode="DE" term="%22Animal+models+of+mental+depression%22">Animal models of mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Rat+behavior%22">Rat behavior</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink>
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  Data: Rationale and objectives: Dl-3-n-Butylphthalide (NBP), a small molecule compound extracted from the seeds of Apium graveolens, possesses a large range of biological effects. Here, we attempted to explore the therapeutic effects of NBP on lipopolysaccharide (LPS)-induced major depressive disorder (MDD) and gain further insight into the underlying mechanisms of the antidepressant effects of NBP.Methods: We evaluated the effect of NBP against LPS-induced behavioral changes in rats. We also examined the inflammation, oxidative stress, and apoptosis markers and analyzed the Nrf2 and NF-κB pathways in the hippocampus of rats following repeated peripheral immune challenge by LPS for 2 weeks (500 μg/kg every other day).Results: Our results indicated that repeated LPS administration induced the rats to a depressive-like state and activated inflammatory response, oxidative stress, and apoptosis reactions in the hippocampus. NBP treatment attenuated the LPS-induced abnormal behavior and ameliorated pathogenic processes in rats with MDD. NBP reduced the inflammatory response with inhibited expression of pro-inflammatory cytokines including IL-1β and IL-6 and downregulated the NF-κB signal pathway. Concurrent with the anti-inflammation action, NBP reduced LPS-induced oxidative reactions in the hippocampus and enhanced Nrf2-targeted signals, as evidenced by increased transcription of antioxidant enzymes and decreased malondialdehyde (MDA) production. In addition, NBP inhibited LPS-induced neuronal apoptosis in the rat brain, as evidenced by decreased apoptosis marker Caspase-3 production and TUNEL assay.Conclusions: These results provide more insight into pathogenesis of MDD and firstly demonstrated the potential antidepressant actions of NBP. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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              Text: Sep2018
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