PMID- 37081966 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230422 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 14 DP - 2023 TI - Licorice extract inhibits the cGAS-STING pathway and protects against non-alcoholic steatohepatitis. PG - 1160445 LID - 10.3389/fphar.2023.1160445 [doi] LID - 1160445 AB - Background: Inflammation and fibrosis are typical symptoms of non-alcoholic steatohepatitis (NASH), which is one of the most common chronic liver diseases. The cGAS-STING signaling pathway has been implicated in the progression of NASH, and targeting this pathway may represent a new therapeutic strategy. Licorice is a widely used herb with anti-inflammatory and liver-protective properties. In this study, we assessed the effect of licorice extract on the cGAS-STING pathway. Methods: Bone marrow-derived macrophages (BMDMs) were treated with licorice extract and then stimulated with HT-DNA, 2'3'-cGAMP, or other agonists to activate the cGAS-STING pathway. Quantitative real-time PCR and western blot were conducted to analyze whether licorice extract could affect the cGAS-STING pathway. Methionine and choline-deficient diet (MCD) was used to induce NASH in mice, which were treated with licorice extract (500 mg/kg) by gavage and/or c-176 (15 mg/kg) by intraperitoneal injection every 2 days. After 6 weeks of treatment, histological analysis of liver tissue was performed, along with measurements of plasma biochemical parameters. Results: Licorice extract inhibits cGAS-STING pathway activation. Mechanistically, it might function by inhibiting the oligomerization of STING. Treatment with licorice extract reduced inflammation and fibrosis in MCD diet-induced NASH mice models. Furthermore, we found that the therapeutic effect of combination treatment with licorice extract and C-176 (STING inhibitor) on the pathology and fibrosis of MCD diet-induced NASH models was similar to that of licorice extract or C-176 administered alone. Conclusion: Licorice extract can inhibit the cGAS-STING pathway and improve hepatic inflammation and fibrosis in NASH mice models. It strongly suggests that licorice extract may be a candidate therapeutic for NASH. CI - Copyright (c) 2023 Luo, Xu, Song, Mu, Wen, Hui, Zhao, Zhan, Bai and Xiao. FAU - Luo, Wei AU - Luo W AD - School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Xu, Guang AU - Xu G AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - School of Traditional Chinese Medicine, Capital Medical University, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Song, Zheng AU - Song Z AD - Peking University 302 Clinical Medical School, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Mu, Wenqing AU - Mu W AD - School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Wen, Jincai AU - Wen J AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Hui, Siwen AU - Hui S AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Zhao, Jia AU - Zhao J AD - School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Zhan, Xiaoyan AU - Zhan X AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Bai, Zhaofang AU - Bai Z AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Xiao, Xiaohe AU - Xiao X AD - School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. AD - Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China. AD - Military Institute of Chinese Materia, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China. LA - eng PT - Journal Article DEP - 20230404 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC10111149 OTO - NOTNLM OT - anti-fibrosis OT - anti-inflammatory OT - cGAS-STING OT - licorice extract OT - non-alcoholic steatohepatitis COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/04/21 06:41 MHDA- 2023/04/21 06:42 PMCR- 2023/04/04 CRDT- 2023/04/21 02:16 PHST- 2023/02/14 00:00 [received] PHST- 2023/03/23 00:00 [accepted] PHST- 2023/04/21 06:42 [medline] PHST- 2023/04/21 06:41 [pubmed] PHST- 2023/04/21 02:16 [entrez] PHST- 2023/04/04 00:00 [pmc-release] AID - 1160445 [pii] AID - 10.3389/fphar.2023.1160445 [doi] PST - epublish SO - Front Pharmacol. 2023 Apr 4;14:1160445. doi: 10.3389/fphar.2023.1160445. eCollection 2023.