PMID- 34983596 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220108 IS - 1749-8546 (Print) IS - 1749-8546 (Electronic) IS - 1749-8546 (Linking) VI - 17 IP - 1 DP - 2022 Jan 5 TI - Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages. PG - 7 LID - 10.1186/s13020-021-00559-3 [doi] LID - 7 AB - BACKGROUND: Stimulator of IFN genes (STING) is highly expressed in the livers of non-alcoholic fatty liver disease (NAFLD) patients and high fat diet (HFD) induced NAFLD mice model. The STING signaling-mediated inflammation has been shown to play a critical role in metabolic disorders. Lingguizhugan decoction (LGZG), a Traditional Chinese herbal decoction, has been applied to treat metabolic disorders for many years. However, whether LGZG can alleviate the progression of NAFLD through inhibiting inflammation remains unclear. This study was to determine the role of STING-mediated inflammation in the HFD-induced hepatic-lipid deposition treated with LGZG. METHODS: The anti-inflammatory and anti-steatotic effects of LGZG in vivo were detected by H&E staining, immunofluorescence and immuno-chemistry. Mice bone-marrow-derived macrophages (BMDMs) and primary liver macrophages were treated with STING-specific agonist (DMXAA), LGZG and its critical components respectively. The treated culture supernatant of BMDMs and primary liver macrophages from each group was co-cultured with palmitic acid-treated mouse primary hepatocytes or mouse liver cell line AML-12 respectively to detect whether the activation of STING-mediated pathway is involved in the anti-steatotic effect of LGZG. The hepatocyte lipid deposition in vivo and in vitro were detected by oil red staining. Mitochondrial DNA release of mouse liver extracts were detected by real time PCR. The expression of proteins and inflammatory cytokines related to STING-TBK1-NF-kappaB pathway was detected by western blotting and ELISA. RESULTS: LGZG significantly ameliorated HFD induced hepatic steatosis, oxidative stress, hepatic mitochondrial damage and mitochondrial DNA release, which was correlated with reduction of the expression level of STING as well as the infiltration of STING-positive macrophages in the livers of HFD fed mice. The critical components of LGZG directly inhibited the activation of STING-TBK1-NF-kappaB pathway in liver macrophages induced by DMXAA, LPS, thereby reducing the release of IFNbeta and TNFalpha. Co-incubating the culture supernatant of LGZG treated liver macrophages and PA-stimulated hepatocytes significantly inhibited the PA-induced lipid deposition. CONCLUSION: This study demonstrates that LGZG can ameliorate HFD-induced hepatic-lipid deposition through inhibiting STING-TBK1-NF-kappaB pathway in liver macrophages, which provides novel insight for elucidating the molecular mechanism of LGZG alleviating HFD induced hepatic steatosis. CI - (c) 2022. The Author(s). FAU - Cao, Lin AU - Cao L AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. guodongcl@163.com. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. guodongcl@163.com. FAU - Xu, Erjin AU - Xu E AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Zheng, Rendong AU - Zheng R AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Zhangchen, Zhili AU - Zhangchen Z AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Zhong, Rongling AU - Zhong R AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Huang, Fei AU - Huang F AD - Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, No. 18 Yangsu Road, Gusu District, Suzhou, 215002, China. FAU - Ye, Juan AU - Ye J AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Sun, Hongping AU - Sun H AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Fan, Yaofu AU - Fan Y AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Xie, Shaofeng AU - Xie S AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Chen, Yu AU - Chen Y AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Xu, Yijiao AU - Xu Y AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. FAU - Cao, Jing AU - Cao J AD - Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing, 210029, China. FAU - Cao, Wen AU - Cao W AD - The Affiliated Jiangning Hospital of Nanjing Medical University, No. 169, Dongshan street, Hushan Road, Jiangning District, Nanjing, 211100, China. caow1900@126.com. FAU - Liu, Chao AU - Liu C AD - Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. liuchao@nfmcn.com. AD - Jiangsu Province Academy of Traditional Chinese Medicine, No. 100, Shizi Street, Hongshan Road, Nanjing, 210028, China. liuchao@nfmcn.com. LA - eng GR - 81804070/National Natural Science Foundation of China/ GR - BK20211388/Nature Science Foundation of Jiangsu province/ GR - SYSD2019148/research program of Suzhou Municipal Science and Technology Bureau/ PT - Journal Article DEP - 20220105 PL - England TA - Chin Med JT - Chinese medicine JID - 101265109 PMC - PMC8728979 OTO - NOTNLM OT - Hepatic steatosis OT - Inflammation OT - Lingguizhugan decoction (LGZG) OT - STING COIS- The authors declare that they have no competing interests. EDAT- 2022/01/06 06:00 MHDA- 2022/01/06 06:01 PMCR- 2022/01/05 CRDT- 2022/01/05 05:42 PHST- 2021/10/04 00:00 [received] PHST- 2021/12/18 00:00 [accepted] PHST- 2022/01/05 05:42 [entrez] PHST- 2022/01/06 06:00 [pubmed] PHST- 2022/01/06 06:01 [medline] PHST- 2022/01/05 00:00 [pmc-release] AID - 10.1186/s13020-021-00559-3 [pii] AID - 559 [pii] AID - 10.1186/s13020-021-00559-3 [doi] PST - epublish SO - Chin Med. 2022 Jan 5;17(1):7. doi: 10.1186/s13020-021-00559-3.