A Novel Antiinflammatory Role for Andrographolide in Asthma via Inhibition of the Nuclear Factor-κB Pathway

Rationale Persistent activation of nuclear factor (NF)-kappa B has been associated with the development of asthma. Andrographolide, the principal active component of the medicinal plant Andrographis paniculata, has been shown to inhibit NF-kappa B activity. Objectives: We hypothesized that andrographolicle may attenuate allergic asthma via inhibition of the NF-kappa B signaling pathway. Methods: BALB/c mice sensitized and challenged with ovalbumin (OVA) developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Serum IgE levels were also determined. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Measurements and Main Results: Andrographolide dose-dependently inhibited OVA-induced increases in total cell count, eosinophil count, and IL-4, IL-5, and IL-13 levels recovered in bronchoalveolar lavage fluid, and reduced serum level of OVA-specific IgE. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, chitinases, Muc5ac, and inducible nitric oxide synthase in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, andrographolicle blocked tumor necrosis factor-alpha-induced phosphorylation of inhibitory kappa B kinase-beta, and downstream inhibitory kappa B alpha degradation, p65 subunit of NF-kappa B phosphorylation, and p65 nuclear translocation and DNA-binding activity. Similarly, andrographolicle blocked p65 nuclear translocation and DNA-binding activity in the nuclear extracts from lung tissues of OVA-challenged mice. Conclusions: Our findings implicate a potential therapeutic value of andrographolicle in the treatment of asthma and it may act by inhibiting the NF-kappa B pathway at the level of inhibitory kappa B kinase-beta activation.