In Vitro Evaluation of the Inhibitory Effects of Linarin on Histamine-Induced Expression of Proinflammatory Cytokines, Mucin 5AC, and Aquaporin 5 in Human Nasal and Bronchial Epithelial Cells.

Allergic rhinitis and asthma are two prevalent chronic allergic conditions in children. Linarin, a glycosylated flavonoid derived from various plants, exhibits a wide range of biological activities. This study aimed to investigate the therapeutic potential of linarin against allergic rhinitis and asthma. In vitro models of allergic rhinitis and asthma were established using human nasal epithelial cells (hNECs) and human bronchial epithelial cells (BEAS-2B), respectively. Linarin treatment inhibited histamine-induced increases in the expression levels of p-p65 and p-IκBα in whole-cell lysates, as well as p65 in nuclear lysates. The histamine-induced activation of MAPK pathways was suppressed by linarin, as evidenced by reduced phosphorylation ratios of ERK (pERK/ERK), JNK (pJNK/JNK), and p38 (pp38/p38). ELISA results further revealed that linarin attenuated histamine-induced secretion of proinflammatory cytokines, including IL-6, IL-8, and MCP-1. Western blot and RT-PCR analyses showed that linarin reversed histamine-induced MUC5AC upregulation and AQP5 downregulation. Notably, the inhibitory effects of linarin were potentiated in the presence of specific inhibitors targeting NF-κB (PDTC), ERK (U0126), p38 (SB203580), and JNK (SP600125). Collectively, these findings demonstrate that linarin suppresses histamine-induced proinflammatory cytokine secretion, MUC5AC upregulation, and AQP5 downregulation in human nasal and bronchial epithelial cells. These effects are mediated through the inhibition of the NF-κB and MAPK pathways. Thus, linarin may serve as a promising therapeutic agent for the treatment of allergic rhinitis and asthma.