Abstract
Introduction: Since ancient times Hypericum perforatum L. named St. John's wort (SJW), has been used in the management of a wide range of applications, including nervous disorders. Development of mood disorders are due to alterations in glutamate metabolism, initiation of inflammatory pathways, and changes of the neuronal plasticity. Previous studies suggest that the glutamatergic system contributes to the pathophysiology of depression. Extracts of SJW have been recommended for the treatment of depression. The aim of the present in vitro study was to evaluate the action of STW3-VI, a special SJW extract in differentiated mouse hippocampal HT-22 neurons. We evaluated the stimulation of neurogenesis, the protective effect against glutamate or N-methyl-D-aspartate receptor induced-excitotoxicity and its anti-inflammatory properties in LPS-activated human macrophages.Results: After 48 h treatment, STW3-VI stimulated the neurite formation by 25% in comparison with the control and showed protective effects against glutamate- or NMDA-induced cytotoxicity by significantly increasing the viability about +25 or +50%. In conjunction with these effects, after pretreatment with STW3-VI, the intracellular reduced glutathione content was significantly 2.3-fold increased compared with the neurons incubated with glutamate alone. Additionally, pre-treatment of human macrophages with STW3-VI showed anti-inflammatory effects after 24 or 48 h concerning inhibition of LPS-induced TNF release by −47.3 and −53.8% (24 h) or −25.0 to −64.8% (48 h).Conclusions: Our data provide new evidence that STW3-VI protects hippocampal cells from NMDA- or glutamate-induced cytotoxicity. Moreover, our results indicate a morphological remodeling by increasing neurite outgrowth and activation of the anti-inflammatory defense by inhibition of the cytokine production in human macrophages after STW3-VI treatment. These protective, neurotrophic and anti-inflammatory properties may be beneficial in the treatment of depressive disorders.
Highlights
Since ancient times Hypericum perforatum L. named St
Upon exposure to differentiation conditions, the hippocampal cells changed to a neuron-like triangular shape and some of these cells were with extended neurites (Figure 1B)
To further explore the anti-inflammatory effect of STW3-VI on human THP-1 macrophages, we examined the expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF) mRNA after STW3-VI pre-treatment, followed by LPS-EB activation (3 h)
Summary
Since ancient times Hypericum perforatum L. named St. John’s wort (SJW), has been used in the management of a wide range of applications, including nervous disorders. The aim of the present in vitro study was to evaluate the action of STW3-VI, a special SJW extract in differentiated mouse hippocampal HT-22 neurons. Stress and neurological injury are naturally diverse; there are common mechanisms of cellular damage. In this context, inflammation and toxicity of glutamate play a major role in a variety of neurological disorders like anxiety, Alzheimer’s or Parkinson’s disease, depression, epilepsy, and ischemic stroke (Tokarski et al, 2008; Haroon et al, 2016). Pro-inflammatory cytokines have a positive and a negative effect on neuronal differentiation and proliferation and may be involved in molecular and cellular mechanisms associated with detrimental alterations in brain-immune communication fundamental for the development of neuropsychiatric syndromes
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