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

doi:10.1016/j.jgr.2021.10.001

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

J Ginseng Res. 2022 Jul;46(4):550-560. doi: 10.1016/j.jgr.2021.10.001. Epub 2021 Oct 13.

Authors

Chang Xu^{1

2}, Liangchang Li^{1

2}, Chongyang Wang^{1

2}, Jingzhi Jiang^{1

2}, Li Li^{1

2}, Lianhua Zhu^{2

3}, Shan Jin^{2

3}, Zhehu Jin^{2

3}, Jung Joon Lee⁴, Guanhao Li^{1

5}, Guanghai Yan^{1

2}

Affiliations

¹ Jilin Key Laboratory for Immune and Targeting Research on Common Allergic Diseases, Yanbian University, Yanji, China.
² Department of Anatomy, Histology and Embryology, Medical College, Yanbian University, Yanji, China.
³ Department of Dermatology, Yanbian University Hospital, Yanji, China.
⁴ College of Pharmacy, Yanbian University, Yanji, China.
⁵ Food Research Center of Yanbian University, Yanji, China.

Abstract

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-mediated anaphylaxis.

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 were detected. ELISA and Western blot measured cytokine and protein levels, respectively.

Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1β and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1β, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, 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-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways.

Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-κB and p38MAPK-Nrf2/NF-κB signaling pathways.

Keywords: AKT-Nrf2; Ginsenoside Rh2 (G-Rh2); MAPK-Nrf2; Mast cell.