Jingfang Granules and Dexamethasone Combination Ameliorates Allergic Asthma in Mice by Modulating Immunity and Oxidative Stress

Allergic asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness, inflammation, and remodeling. Current therapeutic options, often involving corticosteroids like dexamethasone, provide symptomatic relief but can have side effects and may not fully address underlying immune dysregulation. There is a need for synergistic approaches that can enhance anti-inflammatory effects while potentially reducing steroid dependency or improving overall efficacy. This study explores the potential of Jingfang Granules, a traditional Chinese medicine formula, in combination with dexamethasone to offer a more comprehensive therapeutic strategy.

Balb/c mice were induced with an asthma model via ovalbumin (OVA) and aluminum hydroxide. Mice were then divided into seven groups: normal, model, low-dose JF (1 g·kg⁻¹·d⁻¹), medium-dose JF (2 g·kg⁻¹·d⁻¹), high-dose JF (4 g·kg⁻¹·d⁻¹), DEX (1 mg·kg⁻¹·d⁻¹), and a combination of JF (4 g·kg⁻¹·d⁻¹) and DEX (1 mg·kg⁻¹·d⁻¹). Serum IgE and lung IL-4, IL-5, IL-13 levels were quantified by ELISA. WBC, EOS, and LYM counts in BALF were performed, and Th1/Th2 ratios were analyzed by flow cytometry. Non-targeted and targeted metabolomics were used to explore mechanisms, with SOD, CAT, GSH, and MDA levels measured by ELISA to assess oxidative stress. Mitochondrial morphology was observed by transmission electron microscopy, and Western blot detected GPX4, SLC3A2, SLC7A11, and ACSL4 expression to validate ferroptosis-related findings.

Compared to the model group, the combination of Jingfang Granules (JF) and dexamethasone (DEX) demonstrated significant therapeutic effects. The combination therapy significantly decreased serum IgE levels, along with lung IL-4, IL-5, and IL-13 levels, which are key inflammatory cytokines in asthma. Furthermore, the treatment reduced WBC, EOS, and LYM counts in BALF, indicating a reduction in airway inflammation. Crucially, the combination therapy restored the Th1/Th2 balance, suggesting a re-establishment of immune homeostasis. Oxidative stress markers were also positively impacted: the combination increased SOD, CAT, and GSH levels while lowering MDA levels. Metabolomics analysis revealed alterations in metabolic pathways, and Western blot validation confirmed changes in ferroptosis-related proteins.

The combination of Jingfang Granules and dexamethasone significantly decreased inflammatory markers (IgE, IL-4, IL-5, IL-13) and restored Th1/Th2 balance, alongside improving antioxidant capacity in asthmatic mice.