Cryptotanshinone alleviates vasculitis in Kawasaki disease by modulating macrophage-neutrophil interactions

Kawasaki disease (KD) is a form of vasculitis that affects primarily children and can lead to severe cardiovascular complications. Because current treatment options are often ineffective for some patients, new therapeutic strategies are needed. Cryptotanshinone (CTS), a compound derived from Salvia miltiorrhiza Bunge, has shown potential as an anti-inflammatory agent. Herein, in a mouse model of KD induced by Lactobacillus casei cell wall extract (LCWE), CTS was found to significantly decrease inflammation in the aortic root and coronary arteries. This treatment inhibited the activation of macrophages and neutrophils, which are critical contributors to KD. Network pharmacology analysis suggested that CTS modulates the chemokine signaling pathway, thereby inhibiting the recruitment of inflammatory cells and preventing further vasculitis progression. Single-nucleus RNA sequencing (snRNA-seq) revealed that CTS decreased macrophage numbers and chemokine activity, particularly that of Ccl8, and consequently neutrophil recruitment. Our findings suggest that CTS might provide a promising therapeutic option for KD by modulating immune cell interactions and inflammation.