2. Academic Validation
  3. Flavonoids derived from licorice suppress LPS-induced acute lung injury in mice by inhibiting the cGAS-STING signaling pathway

Flavonoids derived from licorice suppress LPS-induced acute lung injury in mice by inhibiting the cGAS-STING signaling pathway

  • Food Chem Toxicol. 2023 May;175:113732. doi: 10.1016/j.fct.2023.113732.
Jincai Wen 1,  Shuanglin Qin 2,  Yurong Li 3,  Ping Zhang 4,  Xiaoyan Zhan 5,  Mingxia Fang 5,  Ce Shi 5,  Wenqing Mu 5,  Wen Kan 5,  Jia Zhao 5,  Siwen Hui 5,  Manting Hou 1,  Hui Li 5,  Xiaohe Xiao 6,  Guang Xu 7,  Zhaofang Bai 8
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, 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, 100039, China.
  • 2 Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China; School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, PR China.
  • 3 Department of Military Patient Management, The Fifth Medical Center of PLA General Hospital, Beijing, 100039, China.
  • 4 Department of Pharmacy, Medical Supplies Center of PLA General Hospital, Beijing, 100039, 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, 100039, China.
  • 6 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, 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, 100039, China. Electronic address: [email protected].
  • 7 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, 100039, China; School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China. Electronic address: [email protected].
  • 8 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, 100039, China. Electronic address: [email protected].
PMID: 36958387 DOI: 10.1016/j.fct.2023.113732
Abstract

In recent years, we have found that the dysregulation of the cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING) pathway leads to the development of immune and inflammatory diseases, therefore, finding compounds that can specifically regulate this pathway is essential for effective regulation of the immune pathway for addressing inflammatory diseases. Licorice Flavonoids (LFs), are active ingredients extracted from the Chinese herb licorice, which has been reported to have strong anti-inflammatory activity in previous studies. Here, we report that LFs inhibit the activation of the cGAS-STING pathway evidenced by the inhibition of the expression of type I interferons and related downstream genes such as interferon-stimulated gene 15 (ISG15) and C-X-C motif chemokine ligand 10 (CXCL10), as well as inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Notably, LFs markedly improve the LPS-induced acute lung injury by inhibiting the excessive activation of cGAS-STING signaling pathway. Mechanistically, LFs treatment leads to the blocking of 2'3'-cyclic GMP-AMP (cGAMP) synthesis resulting in an inhibition of the activation of the cGAS-STING pathway. Our results indicate that LFs is a specific inhibitor of the cGAS-STING pathway, which is suggested to be a potential candidate for the treatment of cGAS-STING pathway-mediated inflammatory diseases.

Keywords

Bronchoalveolar lavage fluid; LPS-Induced acute lung injury; Licorice flavonoids; cGAS-STING.

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