2. Academic Validation
  3. Minimolide F alleviates inflammatory diseases by specifically targeting STING and blocking IRF3 recruitment

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

  • Int Immunopharmacol. 2026 May 1:176:116468. doi: 10.1016/j.intimp.2026.116468.
Jincai Wen 1,  Yingjie Xu 2,  Shuanglin Qin 3,  Yuanyuan Guo 4,  Xianling Wang 2,  Lu Liu 1,  Zongliang Lu 2,  Yulu Yan 3,  Xiaoyan Zhan 2,  Jun Zhao 5,  Xiaohe Xiao 6,  Zhaofang Bai 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 2 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
  • 3 College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
  • 4 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
  • 5 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: [email protected].
  • 6 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: [email protected].
  • 7 School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China; China Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: [email protected].
PMID: 41819671 DOI: 10.1016/j.intimp.2026.116468
Abstract

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.

Keywords

Acute liver injury; Acute lung injury; Inflammatory diseases; Minimolide F; Septic shock; cGAS-STING pathway.

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