Bixin Protects Mice Against Bronchial Asthma Though Modulating PI3K/Akt Pathway

Abstract Background: Accumulating evidence has implicated the potential of natural compounds in treatment of asthma. Bixin is a natural food coloring isolated from the seeds of Bixa Orellana, which possesses anti-tumor, anti-inflammatory and antioxidative properties. Nevertheless, its therapeutic effect in asthma has not been elucidated. Methods: Acute and chronic asthma models of Balb/c mice were established by ovalbumin (OVA) sensitization. For the establishment of a glucocorticoids (GCs) resistant asthma model, Freund’s Adjuvant (CFA) was injected intraperitoneally with OVA. After Bixin treatment, cells in Bronchoalveolar lavage fluid (BALF) were stained with Diff Quick staining and the levels of cytokines were measured by enzyme linked immunosorbent assay (ELISA). The levels of protein in cells and tissues were determined by immunoblotting and/or immunostaining with specific antibodies. The histological changes were determined by Hematoxylin and eosin (H&E), PAS and MASSON staining. Results: Our present study demonstrated that administration of Bixin suppressed allergic airway inflammation and reversed GCs resistance, as well as alleviated airway remodeling and airway hyperresponsiveness (AHR) in asthmatic mice. In vitro studies showed that Bixin treatment could inhibit the development of epithelial-mesenchymal transition (EMT) mediated by transforming growth factor beta (TGF-β) signaling. Importantly, Bixin antagonized activation of phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt) pathway both in vitro and in vivo. Conclusions: Above all, our findings reveal that Bixin functions as a potent antagonist of PI3K/Akt signaling to protect against allergic asthma, highlighting a novel strategy for asthma treatment based on natural products.