Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus

Song, Xiao-Yu; Liu, Bo; Cui, Lingyu; Zhou, Biao; Liu, Weiwei; Xu, Fanxing; Hayashi, Toshihiko; Hattori, Shunji; Ushiki-Kaku, Yuko; Tashiro, Shin‐ichi; Ikejima, Takashi

doi:10.1016/j.physbeh.2017.07.023

Cited by 95 publications

(57 citation statements)

References 55 publications

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“…Silibinin is a flavonoid isolated from Silybum marianum. Silibinin improves the depressive behaviors induced by Aβ42 in rats and also alleviates neuronal damage by suppressing autophagy in the hippocampus [209]. Furthermore, this compound has also been found to protect neurons via suppressing both autophagic cell death and the mitochondrial pathways [210].…”

Section: Role Of Flavonoids In Autophagymentioning

confidence: 99%

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

et al. 2020

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Alzheimer’s disease (AD) is one of the utmost chronic neurodegenerative disorders, which is characterized from a neuropathological point of view by the aggregates of amyloid beta (Aβ) peptides that are deposited as senile plaques and tau proteins which form neurofibrillary tangles (NFTs). Even though advancement has been observed in order to understand AD pathogenesis, currently available therapeutic methods can only deliver modest symptomatic relief. Interestingly, naturally occurring dietary flavonoids have gained substantial attention due to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties as alternative candidates for AD therapy. Experimental proof provides support to the idea that some flavonoids might protect AD by interfering with the production and aggregation of Aβ peptides and/or decreasing the aggregation of tau. Flavonoids have the ability to promote clearance of Aβ peptides and inhibit tau phosphorylation by the mTOR/autophagy signaling pathway. Moreover, due to their cholinesterase inhibitory potential, flavonoids can represent promising symptomatic anti-Alzheimer agents. Several processes have been suggested for the aptitude of flavonoids to slow down the advancement or to avert the onset of Alzheimer’s pathogenesis. To enhance cognitive performance and to prevent the onset and progress of AD, the interaction of flavonoids with various signaling pathways is proposed to exert their therapeutic potential. Therefore, this review elaborates on the probable therapeutic approaches of flavonoids aimed at averting or slowing the progression of the AD pathogenesis.

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Section: Role Of Flavonoids In Autophagymentioning

confidence: 99%

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

et al. 2020

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“…Furthermore, SIL protects the rat brain from methamphetamineinduced memory loss, and streptozotocin-induced cognitive deficits [19]. It has also been shown that SIL, including silymarin, reverses neurochemical and biochemical alterations in the Hipp that are induced by chronic unpredictable mild stress (CUMS) [20,21], which suggests that SIL elicits significant antidepressant-like activities in the CUMS model of depression. SIL is thought to be the primary factor responsible for the pharmacological activities of silymarin; however, this notion has yet to be systematically corroborated and evidence is lacking regarding the efficacy of SIL versus that of silymarin.…”

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confidence: 98%

Silibinin prevents depression-like behaviors in a single prolonged stress rat model: the possible role of serotonin

Lee

Choi

Sur

2020

BMC Complement Med Ther

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Background: Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated. Methods: After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety-and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS.Results: Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp. Conclusions:Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.

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“…There are several publications that report that antidepressants impact autophagy, as has been reported very recently. 43,44 One finding supporting the role of antidepressants in autophagy was that fluoxetine (10 μM), a selective serotonin reuptake inhibitor (SSRI), could promote unblocked autophagic flux by enhancing the fusion of autophagosomes with lysosomes in primary astrocytes. 45 The tricyclic antidepressant amitriptyline was found to increase autophagy in primary neurons and astrocytes, similar to the selective serotonin reuptake inhibitor fluoxetine.…”

Section: Discussionmentioning

confidence: 99%

<p>Weighted Gene Coexpression Network Analysis Identifies Specific Modules and Hub Genes Related to Major Depression</p>

Zhang¹,

Xu²,

Yuan³

et al. 2020

NDT

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Purpose: Despite advances in characterizing the neurobiology of emotional disorders, there is still a significant lack of scientific understanding of the pathophysiological mechanisms governing major depressive disorder (MDD). This study attempted to elucidate the molecular circuitry of MDD and to identify more potential genes associated with the pathogenesis of the disease. Patients and Methods: Microarray data from the GSE98793 dataset were downloaded from the NCBI Gene Expression Omnibus (GEO) database, including 128 patients with MDD and 64 healthy controls. Weighted gene coexpression network analysis (WGCNA) was performed to find modules of differentially expressed genes (DEGs) with high correlations followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to obtain further biological insight into the top three key modules. The protein-protein interaction (PPI) network, the modules from the PPI network, and the gene annotation enrichment of modules were analyzed, as well. Results: We filtered 3276 genes that were considered significant DEGs for further WGCNA analysis. By performing WGCNA, we found that the turquoise, blue and brown functional modules were all strongly correlated with MDD development, including immune response, neutrophil degranulation, ribosome biogenesis, T cell activation, glycosaminoglycan biosynthetic process, and protein serine/threonine kinase activator activity. Hub genes were identified in the key functional modules that might have a role in the progression of MDD. Functional annotation showed that these modules primarily enriched such KEGG pathways as the TNF signaling pathway, T cell receptor signaling pathway, primary immunodeficiency, Th1, Th2 and Th17 cell differentiation, autophagy and RNA degradation and oxidative phosphorylation. These results suggest that these genes are closely related to autophagy and cellular immune function. Conclusion: The results of this study may help to elucidate the pathophysiology of MDD development at the molecular level and explore the potential molecular mechanisms for new interventional strategies.

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Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus

Cited by 95 publications

References 55 publications

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Molecular Insight into the Therapeutic Promise of Flavonoids against Alzheimer’s Disease

Silibinin prevents depression-like behaviors in a single prolonged stress rat model: the possible role of serotonin

<p>Weighted Gene Coexpression Network Analysis Identifies Specific Modules and Hub Genes Related to Major Depression</p>

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