Abstract
ABSTRACTNeuroinflammation is considered a major factor in several neuropsychiatric disorders. Gypenosides (GPS) have pharmacological properties with multiple beneficial effects including antiinflammatory, antioxidative, and protective properties. The present study was performed to examine whether GPS shows anxiolytic-like effects in a model of chronic inflammation induced by injection of lipopolysaccharide (LPS) into the rat hippocampus. The effects of GPS on inflammatory factors in the hippocampus and the downstream mechanisms of these effects were also examined. Introduction of LPS into the lateral ventricle caused inflammatory reactions and anxiety-like symptoms in the rats. Daily treatment with GPS (25, 50, and 100 mg/kg) for 21 consecutive days significantly increased the time spent and number of visits to the open arm in the elevated plus maze test, and significantly increased the number of central zone crossings in the open field test. Moreover, GPS administration significantly reduced the freezing response to contextual fear conditioning, and significantly decreased the levels of proinflammatory mediators, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor-kappaB (NF-κB), levels in the brain. Furthermore, GPS reduced LPS-induced elevated levels of Toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA levels. Taken together, these results suggest that GPS may have anxiolytic-like effects and may have novel therapeutic potential for anxiety-like behaviors caused by neuroinflammation. GPS may be useful for developing an agents for the treatment of neuropsychiatric disorders, such as anxiety, due to its antiinflammatory activities and the modulation of NF-κB/iNOS/TLR4/BDNF.
Highlights
Anxiety disorders, referred to as generalized social anxiety and panic disorders, are the most common mental health disorders, and are characterized by irritability, fatigue, restlessness, muscle tension, sleep problems, intense and persistent fear of social situations, and recurrent and unexpected panic attacks (Yang et al 2017)
GPS reduced LPS-induced elevated levels of Toll-like receptor 4 (TLR4) mRNA and inhibition of brain-derived neurotrophic factor (BDNF) mRNA levels. These results suggest that GPS may have anxiolytic-like effects and may have novel therapeutic potential for anxiety-like behaviors caused by neuroinflammation
The results of the present study clearly indicated that GPS treatment significantly increased the time spent in and the number of entries into the open arms in the elevated plus maze (EPM) and reduced the anxiety index
Summary
Referred to as generalized social anxiety and panic disorders, are the most common mental health disorders, and are characterized by irritability, fatigue, restlessness, muscle tension, sleep problems, intense and persistent fear of social situations, and recurrent and unexpected panic attacks (Yang et al 2017). Many recent studies have demonstrated that neuroinflammatory and sustained increases in various proinflammatory mediators, such as interleukin1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), in the central nervous system are closely related to neuropsychiatric disorders, such as anxiety (Dantzer et al 2008; Vogelzangs et al 2013). Lipopolysaccharide (LPS) is a non-infectious element of the external membranes of gram-negative bacteria that regulates proinflammatory cytokines (Yang et al 2017). LPS is used frequently in research on the biochemical mechanisms of anxiety-like behaviors due to inflammation and for the development of targeted therapies for neurological symptoms in animal models (Jin et al 2017). LPS stimulates proinflammatory cytokine cascades via Toll-like receptor 4 (TLR4) and activation of the nuclear factor-kappaB (NF-κB) system (Fu et al 2013). Nutraceuticals targeting neuroinflammatory mediators have been suggested as novel therapeutic tools for the management of neuropsychiatric and neuroinflammatory disorders (Sulakhiya et al 2016)
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