Daidzein Attenuates Allergic Asthma via NF-κB1 Downregulation and Cytokine Modulation: A Comprehensive Preclinical Evaluation

Background

Bronchial Asthma (BA) is a chronic inflammatory airway disorder strongly associated with immune system dysregulation. Daidzein, a natural isoflavone found in soy, exhibits well-documented anti-inflammatory and immunomodulatory activities, including inhibition of dendritic cell maturation and regulation of effector cell functions.

Objectives

To investigate the anti-asthmatic potential of Daidzein through diverse in vitro and in vivo experimental models, including an Ovalbumin (OVA)-induced allergic asthma rat model.

Materials and Methods

Daidzein was evaluated for multiple pharmacological activities: antioxidant potential using the DPPH radical scavenging assay; antihistaminic activity using an isolated goat tracheal chain; mucolytic activity by measuring egg white viscosity; and mast cell-stabilising effects through clonidine-induced mast cell degranulation and passive paw anaphylaxis. In vivo anti-asthmatic efficacy was assessed in OVA-sensitised rats by analysing body weight changes, Bronchoalveolar Lavage (BAL) fluid cellular infiltration, and levels of IL-4, TNF-α, and IgE in serum and BAL fluid. Lung histopathology and NFKB1 gene expression analysis were also performed.

Results

Daidzein demonstrated significant antioxidant, antihistaminic, mucolytic, mast cell-stabilising, and anti-anaphylactic activities in all in vitro and in vivo screening models. In OVA-induced asthmatic rats, Daidzein pretreatment reduced body weight loss, significantly decreased total inflammatory cells in BAL fluid, and markedly lowered IL-4, TNF-α, and IgE levels. Histopathological studies revealed reduced inflammatory infiltration, decreased goblet cell hyperplasia, and attenuation of airway remodelling. Daidzein also strongly downregulated NFKB1 gene expression, indicating inhibition of NF-κB-mediated inflammatory pathways.

Conclusion

Daidzein exhibits strong anti-asthmatic efficacy by regulating inflammatory cytokines, reducing IgE levels, suppressing NF-κB activation, and protecting lung structure. These findings support Daidzein as a promising and safe multi-target therapeutic candidate for asthma management.