Ginsenoside re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF-κB signaling in microglia

Abstract

Ginsenoside re (G-re) is a panaxatriol saponin and one of the pharmacologically active natural constituents of ginseng (Panax ginseng c.a. Meyer). G-re has antioxidant, anti-inflammatory and antidiabetic effects. The present study aimed to investigate the effects of G-Re on neuroinflammatory responses in lipopolysaccharide (lPS)-stimulated microglia and its protective effects on hippocampal neurons. cytokine levels were measured using eliSa and reactive oxygen species (ROS) levels were assessed using flow cytometry and fluores- cence microscopy. Protein levels of inflammatory molecules and kinase activity were assessed by western blotting. Cell viability was assessed by MTT assay; apoptosis was estimated by Annexin V apoptosis assay. The results revealed that G-Re significantly inhibited the production of IL-6, TNF-α, nitric oxide (NO) and ROS in BV2 microglial cells, and that of NO in mouse primary microglia, without affecting cell viability. G-Re also inhibited the nuclear translocation of NF-κB, and phosphorylation and degradation of iκB-α. in addition, G-re dose-dependently suppressed lPS-mediated phosphorylation of ca2+/calmodulin-dependent protein kinase (caMK)2, caMK4, extracellular signal-regulated kinase (erK) and c-Jun n-terminal kinases (JnK). Moreover, the conditioned medium from lPS-stimulated microglial cells induced HT22 hippocampal neuronal cell death, whereas that from microglial cells incubated with both LPS and G-Re ameliorated HT22 cell death in a dose-dependent manner. These results suggested that G-re suppressed the production of pro-inflammatory mediators by blocking CAMK/erK/JnK/NF-κB signaling in microglial cells and protected hippocampal cells by reducing these inflammatory and neurotoxic factors released from microglial cells. The present findings indicated that G-re may be a potential treatment option for neuroinflammatory disorders and could have therapeutic potential for various neurodegenerative diseases.