LicochalconeB inhibits cGAS-STING signaling pathway and prevents autoimmunity diseases

• DOI: 10.1016/j.intimp.2024.111550
• Publication Date: 2024-01-16T18:58:38Z
• Authors: Wei Luo; Zheng Song; Guang Xu; Hongbo Wang; Wenqing Mu; Jincai Wen; Ping Zhang; Shuanglin Qin; Xiaohe Xiao; Zhaofang Bai
• Keywords: 0301 basic medicine; Molecular Mechanisms of Inflammasome Activation and Regulation; Pharmacology, Toxicology and Pharmaceutics; Cell biology; TANK-binding kinase 1; Innate Immunity to Viral Infection; Immunology; Cancer research; Signal transduction; Engineering; Protein kinase B; Biochemistry, Genetics and Molecular Biology; Molecular Biology; Biology; Immunology and Microbiology; Pharmacology; 0303 health sciences; FOS: Clinical medicine; Innate immune system; Life Sciences; cGAS-STING Pathway; IRF3; Sting; Chemistry; Immune system; Aerospace engineering; Pharmacological Effects of Licorice Roots; MAP kinase kinase kinase; Interferon; Stimulator of interferon genes

Abstract Cytosolic DNA activates the STING (stimulator of interferon genes) signaling pathway to trigger interferon and inflammatory responses that protect against microbial infections and cancer. However, Aicardi–Goutières syndrome (AGS) persistently activates the STING signaling pathway, which can lead to severe autoimmune diseases. We demonstrate herein that Licochalcone B (LicoB), the main component of traditional licorice, is an inhibitor of the STING signaling pathway. We observed that LicoB inhibited the activation of the STING signaling pathway in macrophages. Mechanically, LicoB affected the STING-TBK1-IRF3 signal axis and inhibited the activation of the STING downstream signaling pathway. Furthermore, LicoB inhibited the increase in type I interferon levels in mice induced by the STING agonist CMA. LicoB significantly reduced systemic inflammation in Trex1−/− mice. Our results show that LicoB, a STING signaling pathway inhibitor, is a promising candidate for the treatment of diseases related to STING signaling pathway activation.