The malic acid inhibiting inflammation in ankylosing spondylitis by interfering M1 macrophage polarization
Zhou Ji, Xinzhe Feng, Changhao Han, Shuo Li, Bin Wu, Xu‐Chao Zhang, Shanbang Zhu, Wenwen Tong, Weidong Xu
Abstract
• Malic acid in peripheral blood of patients with AS resulted in the M1-type polarization imbalance of macrophages. • Malic acid intervention can regulate the polarization direction of macrophages. • Supplementation of malic acid inhibited inflammation in ankylosing spondylitis model mice. Ankylosing spondylitis (AS) is a motor system immune disease with significant genetic characteristics, resulting in joint fusion, deformity, rigidity, seriously affecting the quality of life of patients. Inflammatory bowel disease (IBD), characterized by intestinal mucosal damage and inflammatory changes, the most common extra-articular manifestation of AS. Due to the limitations of the application of therapeutic drugs, it is urgent to look for new mechanisms and strategies to effectively inhibit AS inflammation is. The content of malic acid (MA) was significantly decreased in peripheral blood of AS patients, and it was significantly negatively correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). MA dramatically alleviated spinal damage and intestinal inflammation in mouse models of AS induced by β-1, 3-glucan solution. Mechanically, MA suppressed the NF-κB pathway by inhibiting polarization of M1-type macrophages, thereby alleviating spinal and intestinal inflammation. From the perspective of material metabolism, this study explored the mechanism by which MA, an intermediate product of glucose metabolism, reducing M1 polarization of macrophages to inhibit AS inflammation, providing a reliable basis for the pathogenesis research and precise targeted treatment of AS in the later stage.