Journal Article

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

Madhi, Iskander, Shin, Ji Eun, Kim, Ji-Hee, Kim, Younghee

2021

Overview

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 fluorescence 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.

• Publisher: D.A. Spandidos,Spandidos Publications UK Ltd
• Subject: Alzheimer's disease / Animals / Annexin V / Anti-Inflammatory Agents - pharmacology / Antibodies / Antidiabetics / Antioxidants / Apoptosis / Apoptosis - drug effects / Brain / c-Jun protein / Ca2+/calmodulin-dependent protein kinase / Calcium-binding protein / Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Calcium-Calmodulin-Dependent Protein Kinases - metabolism / Calmodulin / Cell culture / Cell death / Cell Death - drug effects / Cytokines - metabolism / Diabetes mellitus / Enzyme-linked immunosorbent assay / Extracellular signal-regulated kinase / Flow cytometry / Fluorescence microscopy / Ginseng / ginsenoside Re / Ginsenosides / Ginsenosides - pharmacology / Hippocampus / Inflammation / Inflammation - metabolism / Interleukin 6 / JNK protein / Kinases / Laboratories / Lipopolysaccharides / Lipopolysaccharides - pharmacology / MAP kinase / Mice / Mice, Inbred ICR / Microglia / Microglia - metabolism / Mitogen-Activated Protein Kinase Kinases - metabolism / Neurodegenerative diseases / neuroinflammation / Neuroinflammatory Diseases - drug therapy / Neuroprotective Agents - pharmacology / Neurotoxicity / NF-kappa B - metabolism / Nitric Oxide - metabolism / Penicillin / Proteins / Reactive oxygen species / Signal Transduction - drug effects / Software / Transcription factors / Tumor Necrosis Factor-alpha - metabolism / Western blotting