The inhibitory effects of Bakuchicin on ovalbumin-induced allergic airway inflammation via regulating M2 macrophage polarization

Abstract

Abstract Asthma is an airway inflammatory disease caused by the activation of many immune cells, including macrophages. Bakuchicin (BKC), a furanocoumarin, has anti-inflammatory properties. This study aimed to evaluate the effects of BKC on allergic airway inflammation and demonstrate the mechanisms of macrophage activation and differentiation. We assessed the effects of BKC by evaluating inflammatory markers in an ovalbumin (OVA)-induced airway inflammation mouse model and macrophage cells. BKC treatment alleviated histological changes, mast cell infiltration, and collagen deposition, and reduced the levels of myeloperoxidase, eosinophil peroxidase, β-hexosaminidase, and transforming growth factor-β in the bronchoalveolar fluid (BALF) and the level of immunoglobulins in serum. BKC ameliorated inflammatory symptoms, including the level of inducible nitric oxide synthase (iNOS) in the lung and the expression and secretion of pro-inflammatory cytokines in serum. BKC treatment reduced not only the level of Th2 cytokines but M2 macrophage marker expression and population in the BALF. In vitro, BKC inhibited LPS-stimulated production of nitric oxide and expression of pro-inflammatory cytokines through inhibition of iNOS, COX-2, Akt, MAPKs, IκBα, and NF-κB in J774 A.1 mouse macrophages. Moreover, BKC suppressed IL-4-induced M2 macrophage polarization by inhibiting arginase-1, YM-1, and Fizz-1 and regulating sirtuin 2 levels in bone marrow derived macrophages. Collectively, BKC may help in the prevention and treatment of airway inflammation by regulating macrophage activation and polarization.