Dioscorea nipponica Makino Relieves Ovalbumin-Induced Asthma in Mice through Regulating RKIP-Mediated Raf-1/MEK/MAPK/ERK Signaling Pathway

PURPOSE: Dioscorea nipponica Makino (DNM) is a traditional herb with multiple medicinal functions. This study is aimed at exploring the therapeutic effects of DNM on asthma and the underlying mechanisms involving RKIP-mediated MAPK signaling pathway. METHODS: An ovalbumin-induced asthma model was established in mice, which was further administrated with DNM and/or locostatin (RKIP inhibitor). ELISA was performed to detect the serum titers of OVA-IgE and OVA-IgG1, bronchoalveolar lavage fluid (BALF) levels of inflammation-related biomarkers, and tissue levels of oxidative stress-related biomarkers. The expression of RKIP was measured by quantitative real-time PCR, Western blot, immunohistochemistry, and immunofluorescence. HE staining was used to observe the pathological morphology of lung tissues. The protein expression of MAPK pathway-related proteins was detected by Western blot. RESULTS: Compared with the controls, the model mice exhibited significantly higher serum titers of OVA-IgE and OVA-IgG1, BALF levels of IL-6, IL-8, IL-13, TGF-β1, and MCP-1, tissue levels of MDA and ROS, lower BALF levels of IL-10 and IFN-γ, and tissue level of GSH. DNM relieved the allergic inflammatory response and oxidative stress in the model mice. DNM also recovered the downregulation of RKIP and the pathological injury of lung tissues in asthma mice. In addition, the Raf-1/MEK/MAPK/ERK pathway in the model mice was blocked by DNM. Silencing of RKIP by locostatin weakened the relieving effects of DNM on asthma through activating the Raf-1/MEK/MAPK/ERK pathway. CONCLUSION: DNM relieves asthma via blocking the Raf-1/MEK/MAPK/ERK pathway that mediated by RKIP upregulation.