1. Ginsenoside 20(R)-Rg3 enhances natural killer cell activity by increasing activating receptor expression through the MAPK/ERK signaling pathway.
- Author
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Lee, Yunhee, Park, Arum, Park, Young-Jun, Jung, Haiyoung, Kim, Tae-Don, Noh, Ji-Yoon, Choi, Inpyo, Lee, Seungjin, and Ran Yoon, Suk
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KILLER cell receptors , *EXTRACELLULAR signal-regulated kinases , *GINSENOSIDES , *CELLULAR signal transduction , *MITOGEN-activated protein kinases , *KILLER cells , *CELL physiology - Abstract
• Ginsenoside Rg3 increasd NK cell cytolytic activity. • Ginsenoside Rg3 activated NK cells through the MAPK/ERK signaling pathway. • Ginsenoside Rg3 enhanced the functional maturation of CB-derived NK cells. • Ginsenoside 20(R)-Rg3 was effective at activating NK cells and was activated through the MAPK/ERK signaling pathway. Ginseng is one of the most widely used herbal remedies for various diseases worldwide. Ginsenoside Rg3 (G-Rg3), the main component of ginseng, possesses several pharmacological properties, including anti-inflammatory, anti-tumor, antioxidant, anti-obesity, and immunomodulatory activities. However, the effect of G-Rg3 on natural killer (NK) cells in humans is not fully understood. Here, we investigated the effect of G-Rg3 on NK cell function and differentiation and elucidated the underlying mechanism. G-Rg3 increased NK cell cytotoxicity and simultaneously increased the expression of NK-activating receptors, NKp44, NKp46, and NKp30. Additionally, G-Rg3 increased the mRNA expression of NK cytolytic molecules, granzyme B and perforin. The expression of CD107a, a marker of NK cell degranulation, also increased in G-Rg3–treated NK cells. We therefore proceeded to identify which MAPK signaling pathway was involved in G-Rg3–mediated cytolytic activity. Treatment with G-Rg3 increased the phosphorylation levels of extracellular signal–regulated kinase (ERK), whereas ERK inhibition eliminated G-Rg3–induced NK cell cytotoxicity, suggesting the involvement of the ERK pathway. G-Rg3 did not affect the rate of differentiation of human cord-blood–derived NK cells; however, it increased the functional maturation of differentiated NK cells and promoted their cytotoxicity. The G-Rg3 isomer, 20(R)-Rg3, effectively activated NK cells via the extracellular signal-regulated kinase (ERK) signaling pathway, whereas 20(S)-Rg3 had no effect on NK cell activity. Altogether, the results demonstrated that 20(R)-Rg3 promoted NK cell activity via activation of the MAPK/ERK pathway, suggesting that 20(R)-Rg3 may be used as an activator of NK cell cytotoxicity for the treatment of diverse types of cancers. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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