Effect of solasodine on mast cell-mediated OVA (ovalbumin)- induced airway inflammation in asthma via the Fyn-Lyn-Syk pathway

Introduction: Current clinical asthma therapeutic drugs can produce a series of adverse effects when used for a long period of time or in high doses, so it is urgent to find new therapeutic strategies. Solasodine can inhibit ovalbumin (OVA)-induced type II inflammation in mice, but the mechanism is still unclear. Mast cell (MCs) degranulation is an important part of allergic reactions, and Src family kinases (SFKs) are involved in the activation of the initiation signal of MC degranulation, and Lyn, Fyn, and Syk among SFKs play important regulatory roles in MC degranulation. Regulation of SFKs can inhibit the MC degranulation process and suppress the occurrence of allergic reactions. Here, we explored the effects of solasodine on OVA-induced asthma in mice and MC-mediated allergic reactions. Methods: Mouse bone marrow-derived mast cells (BMMCs) cells were added with different concentrations (0, 2, 4, 6, 8,10, 12 and 14 µM) of solasodine to select the appropriate concentration. In transforming growth factor (TGF)-β1 treatment of BMMCs, cells were treated with 10 µM solasodine or dexamethasone (Dex), respectively, to analyze the possible mechanisms of action. A mouse model of bronchial asthma was constructed, and the mice were divided into control, OVA, OVA + Dex, OVA + solasodine (1 mg/kg) and OVA + solasodine (10 mg/kg) groups. The histopathological changes in the lungs of the mice were observed by staining with HE, Masson, and Tunel staining. ELISA assay was used to detect the differences between bronchoalveolar lavage fluid (BALF) and serum. IL-4, IL-5, IL-1β, TNF-α and LTD-4 levels were detected by ELISA. BALF inflammatory cells were detected by Wright staining and P-Fyn, P-Lyn and P-Syk protein expression in lung tissues were detected by Western blot. Results: In TGF-β1-induced BMMCs, solasodine significantly reduced the expression of P-Fyn, P-Lyn, and P-Syk, decreased the expression of cytokines IL-6, TNF-α, and LTC ₄ and calcium uptake, as well as inhibited mast cell degranulation. In ova mice, solasodine inhibited OVA-induced airway remodeling, production of IL-4, IL-5, IL-1β, TNF-α, and LTD-4, and degranulation of mast cells in asthmatic mice. Solasodine inhibited the activation of Fyn, Lyn, and Sky and reduced the number of inflammatory cells such as eosinophils, lymphocytes, and neutrophils in lung tissues of asthmatic mice. Conclusion: In this study, we found that solasodine could have a concentration-dependent therapeutic effect on OVA-induced allergic asthma, and solasodine could inhibit the release of mast cell degranulation signature mediator β-HEX and histamine, and the molecular mechanism of its efficacy might be related to its regulation of the intracellular calcium concentration and the IgE/FcεRI-mediated signaling pathways such as P-Fyn/Fyn, P-Lyn/Lyn, P-Syk/Syk, and etc.