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

  • Authors:
    • Iskander Madhi
    • Ji-Hee Kim
    • Ji Eun Shin
    • Younghee Kim
  • View Affiliations / Copyright

    Affiliations: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 46241, Republic of Korea, Korea Nanobiotechnology Center, Pusan National University, Busan 46241, Republic of Korea
    Copyright: © Madhi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 698
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    Published online on: August 3, 2021
       https://doi.org/10.3892/mmr.2021.12337
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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 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.
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Copy and paste a formatted citation
Spandidos Publications style
Madhi I, Kim J, Shin J and Kim Y: Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia. Mol Med Rep 24: 698, 2021.
APA
Madhi, I., Kim, J., Shin, J., & Kim, Y. (2021). Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia. Molecular Medicine Reports, 24, 698. https://doi.org/10.3892/mmr.2021.12337
MLA
Madhi, I., Kim, J., Shin, J., Kim, Y."Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia". Molecular Medicine Reports 24.4 (2021): 698.
Chicago
Madhi, I., Kim, J., Shin, J., Kim, Y."Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia". Molecular Medicine Reports 24, no. 4 (2021): 698. https://doi.org/10.3892/mmr.2021.12337
Copy and paste a formatted citation
x
Spandidos Publications style
Madhi I, Kim J, Shin J and Kim Y: Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia. Mol Med Rep 24: 698, 2021.
APA
Madhi, I., Kim, J., Shin, J., & Kim, Y. (2021). Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia. Molecular Medicine Reports, 24, 698. https://doi.org/10.3892/mmr.2021.12337
MLA
Madhi, I., Kim, J., Shin, J., Kim, Y."Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia". Molecular Medicine Reports 24.4 (2021): 698.
Chicago
Madhi, I., Kim, J., Shin, J., Kim, Y."Ginsenoside Re exhibits neuroprotective effects by inhibiting neuroinflammation via CAMK/MAPK/NF‑κB signaling in microglia". Molecular Medicine Reports 24, no. 4 (2021): 698. https://doi.org/10.3892/mmr.2021.12337
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