Affiliation:
1. Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan
2. Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung 40447, Taiwan
Abstract
Systemic inflammatory response syndrome plays an important role in the development of sepsis. GABAergic and cholinergic pathways activation are considered important for inflammatory response regulation. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-12, IL-10, as well as inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) are important inflammatory mediators involved in the pathogenesis of sepsis. Muscimol, an active compound from the mushroom Amanita muscaria (L.) Lam., is a potent GABAA agonist, inhibits inflammatory response via activating GABAA receptor and vagus nerve. However, the effect of muscimol on lipopolysaccharide (LPS)-induced systemic inflammatory response is still unclear. Therefore, we studied the effects of muscimol on systemic inflammatory response and survival rate in endotoxemic mice. Mice endotoxemia was induced by LPS. Muscimol was given to mice or RAW264.7 cells 30 min before LPS (10 mg/kg, i.p., or 10 ng/mL, respectively). Mice received GABAergic and cholinergic receptor antagonists 30 min before muscimol and LPS. Muscimol decreased TNF-α, IL-1β, IL-12, iNOS-derived NO, and increased IL-10 levels and survival rate after LPS treatment. Muscimol significantly decreased nuclear factor kappa B (NF-κB) activity, increased IκB expression, and decreased pIKK expression in LPS-treated RAW264.7 cells. GABAergic and cholinergic antagonists failed to reverse muscimol’s protection in LPS-treated mice. In conclusion, muscimol protected against systemic inflammatory response in endotoxemic mice may be partially independent of GABAergic and cholinergic receptors.
Publisher
Canadian Science Publishing
Subject
Physiology (medical),Pharmacology,General Medicine,Physiology
Cited by
1 articles.
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