PMID- 32425782 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 11 DP - 2020 TI - Si-Wei-Qing-Gan-Tang Improves Non-Alcoholic Steatohepatitis by Modulating the Nuclear Factor-kappaB Signal Pathway and Autophagy in Methionine and Choline Deficient Diet-Fed Rats. PG - 530 LID - 10.3389/fphar.2020.00530 [doi] LID - 530 AB - Si-Wei-Qing-Gan-Tang (SWQGT) is a Chinese medicine formula that is widely used as a folk remedy of herbal tea for the treatment of chronic hepatitis, like non-alcoholic steatohepatitis (NASH), around Ganzhou City (Jiangxi province, China). However, the underlying mechanisms of this formula against NASH are still unknown. This study aimed to explore the effect and mechanisms of SWQGT against NASH. A network pharmacology approach was used to predict the potential mechanisms of SWQGT against NASH. Then a rat model of NASH established by feeding the methionine and choline deficient (MCD) diet was used to verify the effect and mechanisms of SWQGT on NASH in vivo. SWQGT (1 g/kg/d and 3 g/kg/d) were given by intragastric administration. Body weight, liver weight, serum biochemical indicators, liver triglyceride and total cholesterol were all measured. Tumor necrosis factor-alpha (TNF-alpha), Interleukin (IL)-1beta, IL-6 levels in the livers were evaluated using ELISA. Hematoxylin and eosin (HE) and Oil Red O staining were used to determine histology, while western blot was used to assess the relative expression levels of the nuclear factor-kappaB (NF-kappaB) pathway- and autophagy-related proteins. Functional and pathway enrichment analyses revealed that SWQGT obviously influenced inflammation-related signal pathways in NASH. Furthermore, in vivo experiment showed that SWQGT caused a reduction in liver weight and liver index of MCD diet-fed rats. The formula also helped to reduce hepatomegaly and improve pathological liver changes and hepatic steatosis. SWQGT likewise reduced liver TNF-alpha, IL-1beta, and IL-6 levels and down-regulated p-NF-kappaB p65, p-p38 MAPK, p-MEK1/2, p-ERK1/2, p-mTOR, and p62, while up-regulating p-ULK1 and LC3II protein expression levels. SWQGT could improve NASH in MCD diet-fed rats, and this effect may be associated with its down-regulation of NF-kappaB and activation of autophagy. CI - Copyright (c) 2020 Xiao, Liang, Ge, Qiu, Wan, Wu, Fei, Peng and Zeng. FAU - Xiao, Lingyun AU - Xiao L AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. AD - Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China. FAU - Liang, Shu AU - Liang S AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. FAU - Ge, Lanlan AU - Ge L AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. AD - Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China. FAU - Qiu, Shuling AU - Qiu S AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. FAU - Wan, Haoqiang AU - Wan H AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. AD - Department of Pathology (Longhua Branch), 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. FAU - Wu, Shipin AU - Wu S AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. FAU - Fei, Jia AU - Fei J AD - Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China. FAU - Peng, Shusong AU - Peng S AD - Department of Pathology (Longhua Branch), 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. FAU - Zeng, Xiaobin AU - Zeng X AD - Centre Lab of Longhua Branch and Department of Infectious Disease, 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, Shenzhen, China. AD - Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, China. LA - eng PT - Journal Article DEP - 20200501 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC7206618 OTO - NOTNLM OT - NF-kappaB OT - Si-Wei-Qing-Gan-Tang OT - autophagy OT - inflammation OT - network pharmacology OT - non-alcoholic steatohepatitis EDAT- 2020/05/20 06:00 MHDA- 2020/05/20 06:01 PMCR- 2020/05/01 CRDT- 2020/05/20 06:00 PHST- 2019/09/13 00:00 [received] PHST- 2020/04/03 00:00 [accepted] PHST- 2020/05/20 06:00 [entrez] PHST- 2020/05/20 06:00 [pubmed] PHST- 2020/05/20 06:01 [medline] PHST- 2020/05/01 00:00 [pmc-release] AID - 10.3389/fphar.2020.00530 [doi] PST - epublish SO - Front Pharmacol. 2020 May 1;11:530. doi: 10.3389/fphar.2020.00530. eCollection 2020.