Anxiolytic Effects of 8-O-Acetyl Shanzhiside Methylester on Acute and Chronic Anxiety via Inflammatory Response Inhibiti
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ORIGINAL ARTICLE
Anxiolytic Effects of 8-O-Acetyl Shanzhiside Methylester on Acute and Chronic Anxiety via Inflammatory Response Inhibition and Excitatory/Inhibitory Transmission Imbalance Ting Sun 1 & Li Luo 1 & Qin-Qin Tian 2 & Wen-Ju Wang 3 & Qing-Qing Liu 1 & Le Yang 1 & Kun Zhang 1 & Wei Zhang 4 & Ming-Gao Zhao 1 & Qi Yang 1 Received: 2 February 2020 / Revised: 24 March 2020 / Accepted: 7 April 2020 # The Author(s) 2020
Abstract Anxiety leads to a global decline in quality of life and increase in social burden. However, treatments are limited, because the molecular mechanisms underlying complex emotional disorders are poorly understood. We explored the anxiolytic effects of 8O-acetyl shanzhiside methylester (8-OaS), an active component in Lamiophlomis rotata (L. rotata; Benth.) or Kudo, a traditional herb that has been shown to be effective in the clinical treatment of chronic pain syndromes in China. Two mouse anxiety models were used: forced swimming stress (FSS)–induced anxiety and complete Freund’s adjuvant (CFA)–induced chronic inflammatory pain. All animal behaviors were analyzed on the elevated plus maze and in the open-field test. 8-OaS significantly ameliorated anxiety-like behaviors in both anxiety models and inhibited the translation enhancement of GluN2A, GluN2B, and PSD95. Moreover, a reduction in GABA receptors disrupted the excitatory/inhibitory (E/I) balance in the basolateral amygdala (BLA), indicated by increased excitatory and decreased inhibitory presynaptic release. 8-OaS also blocked microglia activation and reduced the phosphorylation of p38, c-Jun N-terminal kinase (JNK), NF-κB p65, and tumor necrosis factor alpha (TNF-α) in the BLA of anxiety mice. 8-OaS exhibits obvious anxiolytic effects by regulating the excitatory/inhibitory (E/I) synaptic transmission and attenuating inflammatory responses in the BLA. Keywords Anxiety . 8-O-Acetyl shanzhiside methylester . Excitatory/inhibitory balance . Basolateral amygdala . Inflammatory response
Introduction Ting Sun and Li Luo contributed equally to this work. * Ming-Gao Zhao [email protected] * Qi Yang [email protected] 1
Precision Pharmacy & Drug Development Center, Department of Pharmacy, Tangdu Hospital, the Fourth Military Medical University, Xi’an 710038, Shaanxi Province, People’s Republic of China
2
Department of Chemistry, School of Pharmacy, the Fourth Military Medical University, Xi’an 710032, China
3
Student Brigade, the Fourth Military Medical University, Xi’an 710032, China
4
Department of Pharmacy, Xijing Hospital, the Fourth Military Medical University, Xi’an 710032, China
Anxiety disorder is highly common worldwide, with an estimated prevalence of 15% in developed countries, and seriously affects people’s life and work (Wu et al. 2008). Anxiety disorder is a chronic and functional disability with high psychological pressure, characterized by overwhelming stress, attention difficulties, and physiological symptoms such as muscle tension and insomnia (Beery and Kaufer 2015; Du et al. 2019). Antidepressants and benzo
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