Abstract
Gelsemine is an active principle and a major alkaloid found in Gelsemium genus of plants belonging to the Loganiaceae family. The aim of the present study was to explore whether gelsemine exerts anxiolytic effects on a mouse model of chronic-unpredictable-mild-stress (CUMS)-induced anxiety-like behaviors. NOD-like receptor protein 3 (NLRP3) inflammasome, downregulated cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were also evaluated as potential mechanisms. First, gelsemine reversed a CUMS-induced decrease in body-weight gain in mice. Next, gelsemine alleviated CUMS-induced anxiety-like behaviors, as evidenced by the increased distance traveled in the central zone of the open-field test, both the increased percentage of time spent and distance traveled in the light compartment, the increased number of transitions between compartments in the light/dark-transition test, and the increased percentage of entries and time spent in the open arm of the elevated plus-maze. In addition, gelsemine decreased the levels of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6, in the hypothalamus and hippocampus of CUMS mice. Interestingly, further investigations revealed that gelsemine inhibited the CUMS-induced activation of NLRP3-inflammasome pathways and downregulated CREB and BDNF overexpression in the hypothalamus. In summary, gelsemine alleviated anxiety-like behaviors in the CUMS-induced mouse model. Gelsemine exerted its anxiolytic effects by modulating the NLRP3 and CREB/BDNF pathways.
Highlights
Anxiety disorders are the most common psychiatric illnesses among children and adolescents, as 10–20% of individuals have experienced this disorder during their lifetime [1]
A mouse model of anxiety induced by CUMS was constructed to ensure that our results would closely resemble the clinicopathological features of anxiety disorders
Ten mice each from the control group and the CUMS-model group were randomly selected to perform the sucrosepreference test (SPT) and open-field test (OFT) in order to ensure the reliability of subsequent experiments and the successful establishment of the model
Summary
Anxiety disorders are the most common psychiatric illnesses among children and adolescents, as 10–20% of individuals have experienced this disorder during their lifetime [1]. Drug therapy is a typical first-line treatment, and the effect of drug treatment is greater than psychological interventions [9]. The anti-anxiety drugs used in the clinic mainly include antidepressant anxiolytics, benzodiazepine anxiolytics, nonbenzodiazepine anxiolytics, and anticonvulsant anxiolytic drugs [10]. Many pharmacological treatment options are available, many anti-anxiety medications used to treat anxiety have negative side effects, including addiction, depression, suicide, seizures, sexual dysfunction, and headaches, among others [10]. Novel anti-anxiety drugs with better tolerance and lower side effects must be developed.The development of novel therapies for the treatment of anxiety disorders from natural resources inspired by traditional medicine has attracted increasing attention, which is one of the important directions of new drug research and development [1,11]
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