Effect of improved Yupingfeng powder prescription on interleukin-33/suppression of tumorigenicity 2 pathway in mice with ovalbumins-induced allergic rhinitis.

OBJECTIVE

To identify the main active ingredients of Improved Yupingfeng Powder prescription (IYPFP, ) and investigate its anti-inflammatory effects and underlying mechanisms in ovalbumins (OVA)-induced allergic rhinitis (AR) in mice.

METHODS

Bagg Albino/substrain mice were sensitized with OVA emulsified in aluminum hydroxide adjuvant, followed by intranasal challenge to establish AR models. Treatment groups received IYPFP (1.5 or 4.5 g/kg) via daily gavage for 14 d. The nasal mucosa tissues were collected for pathological observation. The expression of OVA-specific immunoglobulin E (IgE), histamine, and interleukin-33 (IL-33) was detected by enzyme-linked immunosorbent assay. IL-5, IL-13, IL-33, suppression of tumorigenicity 2 (ST2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the nasal mucosa and lung were detected by quantitative polymerase chain reaction and Western blot. High performance liquid chromatography and ultra-high performance liquid chromatography quadrupole exactive orbitrap mass spectrometry were used to detect the chemical fingerprints of IYPFP, and the chemical compositions of plasma from rats treated with IYPFP at 0.5, 1, 1.5, 2, 3, 4 and 6 h, respectively. Virtual screening of bioactive compounds was conducted through molecular docking targeting IL-33/ST2 pathway proteins.

RESULTS

Eight chemical compounds of IYPFP were accurately identified, they are prim-O-glucosylcimifugin (peak 2), calycosin-7-O-β-D-glucoside (peak 4), cimifugin (peak 5), 5-O-methylvisammioside (peak 6), sec-O-glucosylhamaudol (peak 12), calycosin (peak 15), formononetin (peak 19), and magnolin (peak 21). Compared with the OVA model group, IYPFP alleviated the nasal symptoms, improved nasal mucosal injury and downregulated the levels of OVA-specific IgE, histamine and IL-33. Additionally, IYPFP reduced the levels of IL-5, IL-13, TNF-α, IL-33, and ST2 in the lungs, but upregulated IFN-γ. Molecular docking confirmed that eight representative compounds of IYPFP had good binding properties with IL-5, IL-13, IFN-γ, histamine, IL-33 and ST2, and were able to inhibit the activation of the IL33/ST2 inflammatory pathway.

CONCLUSION

This study demonstrates that IYPFP ameliorates AR by modulating IL-33/ST2 pathway which provides a theoretical basis for the clinical treatment of patients with AR.