Polygonatum kingianum alleviates diabetic inflammation via the Mef2d/Rufy4-autophagy axis to drive macrophage M2 polarisation

Chronic inflammation associated with abnormal activation of macrophages is an important promoter of type 2 diabetes (T2D) and its complications. However, there are no effective strategies for mitigating chronic inflammation. This study demonstrated that Polygonatum kingianum (P.K.) can promote macrophages M2 polarisation and increase the expression of anti-inflammatory cytokines. The mechanism involved P.K. upregulation of Mef2d expression, a key gene involved in M2 macrophage polarisation. Mef2d targeted and promoted the expression of Rufy4, thereby activating autophagy and ultimately resulting in M2 macrophage polarisation. P.K. significantly increased the number of M2 macrophages in the bone marrow and kidney while concurrently reducing the serum levels of CRP in a murine model of T2D. In summary, this study confirms that P.K. induces macrophage M2 polarisation via the Mef2d-Rufy4-autophagy pathway, which alleviates chronic inflammation associated with T2D. This study lays a foundation for the prevention and treatment of vascular complications in patients with T2D.