Minimolide F alleviates inflammatory diseases by specifically targeting STING and blocking IRF3 recruitment.

The activation of the STING signaling pathway is closely related to the onset and development of inflammatory diseases. When the cGAS protein recognizes cytoplasmic DNA, it promotes the excessive production of type I interferons and proinflammatory cytokines, leading to excessive inflammatory responses. There is a correlation between this and the mechanisms underlying inflammatory diseases such as systemic inflammatory response, septic shock, and acute liver injury. Moderate regulation of STING signaling activation has become a new target and direction for the treatment of inflammatory diseases. In this study, we found that Minimolide F (MF), an active component of Sophorae Tonkinensis Radix et Rhizoma can specifically inhibit the activation of the cGAS-STING pathway and the accompanying inflammatory response. Mechanistically, MF can target and bind to STING, thereby inhibiting the binding of STING to IRF3. Additionally, MF can inhibit the activation of the cGAS-STING signal in vivo and exhibits great therapeutic effects in septic shock acute liver injury and acute lung injury models. In summary, our study found that MF has therapeutic potential in inflammatory diseases mediated by cGAS-STING, which provides a reference for the development of clinical treatments for STING-driven inflammatory diseases.