1. S-equol, a metabolite of dietary soy isoflavones, alleviates lipopolysaccharide-induced depressive-like behavior in mice by inhibiting neuroinflammation and enhancing synaptic plasticity
- Author
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Ying Chen, Jing Sun, Bei Fan, Qiong Wang, Yingyu Zhang, Rongjing Gao, Xinmin Liu, Fengzhong Wang, Ning Jiang, and Cong Lu
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Serotonin ,Interleukin-1beta ,Anti-Inflammatory Agents ,Pharmacology ,Hippocampus ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Animals ,Medicine ,Swimming ,Neuroinflammation ,Inflammation ,Neuronal Plasticity ,Depression ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,NF-kappa B ,food and beverages ,General Medicine ,Synapsin ,Antidepressive Agents ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,Equol ,030104 developmental biology ,Monoamine neurotransmitter ,Hindlimb Suspension ,chemistry ,Astrocytes ,Synaptic plasticity ,TLR4 ,Cytokines ,(S)-Equol ,Antidepressant ,business ,030217 neurology & neurosurgery ,Kynurenine ,Signal Transduction ,Food Science - Abstract
Systemic injection with lipopolysaccharide can lead to depressive-like behavior in experimental animals by inducing neuroinflammation and is considered to be a classic model of depression. S-equol is a major metabolite of dietary soy isoflavones with antioxidant and anti-inflammatory effects, and it has many beneficial effects on human health, including alleviation of menopausal symptoms, osteoporosis, cancer, obesity, chronic kidney disease, and cognitive dysfunction. A recent study reported that S-equol inhibited lipopolysaccharide-stimulated neuroinflammation in astrocytes. However, there is no research on the antidepressant-like effects of S-equol. Therefore, the present study was conducted to evaluate the antidepressant-like effects of S-equol in a lipopolysaccharide-induced depression model in mice and explore its underlying mechanisms. Our results demonstrated that treatment with S-equol (10, 20 and 40 mg kg-1) for 19 days markedly reversed the behavior of acute LPS (1.0 mg kg-1) treated mice in sucrose preference, tail suspension and forced swimming tests, exerting antidepressant-like effects. In addition, S-equol administration significantly decreased the levels of pro-inflammatory cytokines (tumor necrosis factor, interleukin-6, interleukin-10, interleukin-1β), increased the levels of 5-hydroxytryptamine and norepinephrine, and normalized the release of tryptophan and kynurenine in the hippocampi of lipopolysaccharide-treated mice. Moreover, treatment with S-equol significantly up-regulated the expression of synaptic plasticity-related proteins (phospho synapsin, synapsin, postsynaptic density-95) and down-regulated the toll-like receptor 4/nuclear factor kappa B signaling pathway in the hippocampi of lipopolysaccharide-treated mice. These findings demonstrated that S-equol significantly alleviated the depressive-like behavior induced by acute systemic injection of LPS, and its antidepressant action was related to mediation of neuroinflammation via the TLR4/NF-κB signaling pathway, normalization of the monoamine neurotransmitter levels, reversal of tryptophan metabolism dysfunction, and enhancement of synaptic plasticity. The current study provides insight into the potential of S-equol in the prevention of depression.
- Published
- 2021
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