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        Effects of G-Rh2 on mast cell-mediated anaphylaxis via AKT-Nrf2/NF-κB and MAPK-Nrf2/NF-κB pathways

        Chang Xu,Liangchang Li,Chongyang Wang,Jingzhi Jiang,Li Li,Lianhua Zhu,Shan Jin,Zhehu Jin,Jung Joon Lee,Guanhao Li,Guanghai Yan 고려인삼학회 2022 Journal of Ginseng Research Vol.46 No.4

        Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediatedanaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation weredetected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-a, IL-4, IL-8, IL-1b andthe degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lungtissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmaticmice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the earthickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histaminerelease and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1b, TNF-a, IL-8, andIL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation ofmast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in adose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCg2, PI3KERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-kB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT,p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-kB signaling pathway activation byactivating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by theAKT-Nrf2/NF-kB and p38MAPK-Nrf2/NF-kB signaling pathways

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