Immunomodulatory Effects of Huaier Extract on Th1/Th2 Polarization Through IL-33/ST2 Axis Regulation in Allergic Rhinitis Pathogenesis

This study aims to systematically evaluate the immunomodulatory effects of Huaier extract in allergic rhinitis, as well as the underlying mechanisms by which it regulates T helper 1 (Th1) / T helper 1 (Th2) cell imbalance to exert its therapeutic effects. An ovalbumin (OVA)-induced allergic rhinitis mouse model was established. Twenty-four 6-week-old female BALB/c mice were randomly assigned to four groups (n = 6 per group): Control (phosphate-buffered saline [PBS] only), OVA-sensitized/challenged (Model), OVA + dexamethasone (Dex, 1 mg/kg), and OVA + Huaier extract (Huaier, 50 mg/kg). Intraperitoneal sensitization was conducted on days 1, 7, and 14 using 200 µl of PBS containing 50 µg OVA and 2 mg aluminum hydroxide (alum). From days 21 to 27, the Model, Dex, and Huaier groups underwent alternate-day intranasal OVA challenges, with concurrent daily intranasal treatments: Huaier extract for the Huaier group, dexamethasone for the Dex group, and PBS for the Model group. On day 27, nasal symptoms in the mice were recorded. The following day (day 28), blood samples and nasal mucosal tissues were collected for subsequent analyses. Nasal mucosal histopathology was assessed via hematoxylin-eosin (H&E) staining. Serum levels of specific immunoglobulin E (sIgE), Th1/Th2-associated cytokines, and pro-inflammatory mediators were measured using enzyme-linked immunosorbent assay (ELISA). Th1/Th2-related cytokines and proteins in the IL-33/ST2 pathway were evaluated via immunohistochemistry. Huaier reduced nasal symptom scores. Specifically, we found that after treatment with Huaier or dexamethasone (Dex), the symptom scores of mice (3.33 ± 0.52 and 3.17 ± 0.75, respectively) were significantly lower compared with the Model group (P < 0.001). Notably, Huaier exhibited efficacy comparable to that of dexamethasone (P > 0.05). Huaier also ameliorated the abnormal activation of the IL-33/ST2 pathway in mice with allergic rhinitis and alleviated nasal inflammation. This anti-inflammatory effect was associated with increased levels of suppressed Th1 cytokines, alongside decreased levels of elevated Th2 cytokines, OVA-specific immunoglobulin E (OVA-sIgE), IL-33, and ST2. In a murine model of allergic rhinitis, Huaier extract attenuated inflammatory responses and restored Th1/Th2 immune balance. This therapeutic effect may be mediated through regulation of the IL-33/ST2 signaling pathway.