Cimifugin Mitigates Allergic Response and Inflammatory Response in Allergic Rhinitis via Modulation of SIRT2

Abstract

Background: Allergic rhinitis (AR) is a common autoimmune disease of the upper airway accompanied by prominent comorbid conditions. Cimifugin is a major constituent of Saposhnikovia divaricatae that is widely implied in the treatment of allergic diseases. This study aims to investigate the impacts of cimifugin on the process of AR and to ascertain the indistinct underlying mechanisms. Methods: Initially, AR mice models were developed and allergic symptoms in mice were observed. Hematoxylin and eosin (H&E) staining and toluidine blue staining were employed to assess the infiltration of eosinophils and mast cells in the nasal mucosa tissues of mice. Moreover, serum ovalbumin (OVA)-specific immunoglobulins levels, and levels of Th2 and Th1 cytokines were evaluated in the nasal lavage fluid using their corresponding enzyme-linked immunosorbent assay (ELISA) Kits. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay and western blot analysis were used to examine cell apoptosis. Furthermore, western blot analysis was used to determine the expression level of Sirtuin 2 (SIRT2) both in vitro and in vivo. Additionally, cell counting kit-8 (CCK-8) assay was utilized to examine cell viability and ELISA was used to estimate inflammatory levels. Moreover, reverse transcription-quantitative PCR (RT-qPCR), western blot analysis and IF assay were employed to determine the expression levels of mucin 5AC (MUC5AC). Results: It was noticed that cimifugin eased allergic symptoms and nasal mucosal inflammation, declined serum OVA-specific immunoglobulins and Th2 cytokines levels, and suppressed apoptosis in the OVA-induced AR murine model. Moreover, the cimifugin targeted SIRT2 and fortified SIRT2 expression both in vitro and in vivo. Furthermore, SIRT2 interference reversed the impacts of cimifugin on the inflammation and mucus production in interleukin-13 (IL-13)-exposed human nasal epithelial cells (hNECs). Conclusion: In conclusion, the cimifugin protected against OVA-triggered allergic symptoms and inflammation in AR by elevating SIRT2 expression.