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

被引:16
作者
Wen, Jincai [1 ,2 ,6 ]
Qin, Shuanglin [2 ,3 ]
Li, Yurong [4 ]
Zhang, Ping [5 ]
Zhan, Xiaoyan [2 ,6 ]
Fang, Mingxia [2 ,6 ]
Shi, Ce [2 ,6 ]
Mu, Wenqing [2 ,6 ]
Kan, Wen [2 ,6 ]
Zhao, Jia [2 ,6 ]
Hui, Siwen [2 ,6 ]
Hou, Manting [1 ,2 ,6 ]
Li, Hui [2 ,6 ]
Xiao, Xiaohe [1 ,2 ,6 ,8 ]
Xu, Guang [2 ,6 ,7 ,8 ]
Bai, Zhaofang [2 ,6 ,8 ]
机构
[1] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China
[2] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Hepatol, Beijing 100039, Peoples R China
[3] Hubei Univ Sci & Technol, Xianning Med Coll, Sch Pharm, Xianning, Peoples R China
[4] Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Mil Patient Management, Beijing 100039, Peoples R China
[5] Peoples Liberat Army Gen Hosp, Med Supplies Ctr, Dept Pharm, Beijing 100039, Peoples R China
[6] Chinese Peoples Liberat Army Gen Hosp, China Mil Inst Chinese Mat, Med Ctr 5, Beijing 100039, Peoples R China
[7] Capital Med Univ, Sch Tradit Chinese Med, Beijing 100069, Peoples R China
[8] Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Hepatol, Beijing 100039, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金; 北京市自然科学基金;
关键词
Licorice flavonoids; cGAS-STING; LPS-Induced acute lung injury; Bronchoalveolar lavage fluid; INFLAMMATION; PROTECTS;
D O I
10.1016/j.fct.2023.113732
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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-alpha (TNF-alpha). 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.
引用
收藏
页数:11
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