Abstract
For several thousand years, Ganoderma lucidum (Ling-Zhi in Chinese and Reishi in Japanese) has been widely used as a traditional medication for the prevention and treatment of various diseases in Asia. Its major biologically active components, ganoderic acids (GAs), exhibit significant medicinal value due to their anti-inflammatory effects. Dysregulation of microglial function may cause seizures or promote epileptogenesis through release of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. At present, only little information is available on the effects of GAs on microglia-mediated inflammation in vitro and/or in vivo. The present study aimed to investigate the role of GA-A on microglia-mediated inflammation in vitro. In addition, the effect of GA-A on lipopolysaccharide (LPS)-evoked alterations in mitochondrial metabolic activity of microglia was evaluated. The results of the present study demonstrated that GA-A significantly decreased LPS-induced IL-1β, IL-6 and TNF-α release from mouse-derived primary cortical microglial cells in a concentration-dependent manner. GA-A treatment reduced LPS-induced expression of nuclear factor (NF)-κB (p65) and its inhibitor, demonstrating that non-toxic suppression of IL-1β, IL-6 and TNF-α production by GA-A is, at least in part, due to suppression of the NF-κB signaling pathway. In addition, the LPS-induced stimulation of mitochondrial activity of microglial cells was abolished by co-treatment with GA-A. Thus, GA-A treatment may be a potential therapeutic strategy for epilepsy prevention by suppressing microglia-derived proinflammatory mediators.