PMID- 34536264 OWN - NLM STAT- MEDLINE DCOM- 20220406 LR - 20220406 IS - 1932-8494 (Electronic) IS - 1932-8486 (Linking) VI - 304 IP - 11 DP - 2021 Nov TI - Network pharmacology-based investigation to explore the effect and mechanism of Erchen decoction against the nonalcoholic fatty liver disease. PG - 2605-2619 LID - 10.1002/ar.24770 [doi] AB - This study aimed to uncover the potential mechanism of Erchen decoction (ECD) on the amelioration of nonalcoholic fatty liver disease (NAFLD). Network pharmacology and bioinformatics were used to determine the active components of ECD and its potential target in treating NAFLD. High fat diet (HFD)-induced NAFLD mice model was used. Liver tissues were stained with hematoxylin and eosin, and Oil Red O. Serum lipid profiles and hepatic inflammatory molecules in lipopolysaccharide (LPS)/Toll-like receptor-4 (TLR-4) pathway were confirmed by enzyme-linked immunosorbent assay. Intestinal barrier function, including intestinal epithelial tight junction (IETJ) proteins, fecal short-chain fatty acids (SCFAs) concentration and intestinal microbiota composition, was also assessed. Screening relevant databases revealed 123 active components and 158 potential target proteins in ECD, as well as 1,783 differential genes for NAFLD. Enrichment analyses predicted that the regulation of LPS, cholesterol metabolism and inflammatory pathways might be the underlying mechanisms of ECD in NAFLD treatment. ECD ameliorated the multi-profiles of NAFLD and reversed the high levels of inflammatory molecules such as, serum LPS, hepatic TLR-4, tumor necrosis factor-alpha, and interleukin-1beta. Additionally, ECD upregulated the concentration levels of IETJ proteins and fecal SCFAs. 16s RNA sequencing indicated that ECD can improve the gut microbiota, such as Akkermansia, Clostridium XIVa, Coprococcus, and Ruminococcus. The current study demonstrated that ECD can reverse the HFD-induced intestinal barrier dysfunction, thereby reducing the LPS translocation and alleviating the hepatic inflammation, and eventually exhibiting a protective effect against NAFLD. CI - (c) 2021 American Association for Anatomy. FAU - Liu, Haiyan AU - Liu H AUID- ORCID: 0000-0001-9955-1758 AD - Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou, China. AD - Digestive Disease Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China. FAU - Xu, Jie AU - Xu J AD - Graduate School, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Li, Hui AU - Li H AD - Graduate School, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Zhang, Lina AU - Zhang L AD - Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, China. FAU - Xu, Pingzhen AU - Xu P AUID- ORCID: 0000-0001-5506-4640 AD - Endoscopy Center, Tongde Hospital of Zhejiang Province, Hangzhou, China. LA - eng GR - 82004333/National Natural Science Foundation of China/ GR - 2016ZX09101069/National science and technology major special projects for the major new drug innovation/ GR - 2017-XK-B02/The 13th Five-Year Plan of Zhejiang Provincial Key Discipline Construction of Traditional Chinese Medicine/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210918 PL - United States TA - Anat Rec (Hoboken) JT - Anatomical record (Hoboken, N.J. : 2007) JID - 101292775 SB - IM MH - Animals MH - Diet, High-Fat/adverse effects MH - *Gastrointestinal Microbiome MH - Liver/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Network Pharmacology MH - *Non-alcoholic Fatty Liver Disease/drug therapy OTO - NOTNLM OT - Erchen decoction OT - intestinal barrier function OT - network pharmacology OT - nonalcoholic fatty liver disease OT - traditional Chinese medicine EDAT- 2021/09/19 06:00 MHDA- 2022/04/07 06:00 CRDT- 2021/09/18 12:13 PHST- 2021/07/17 00:00 [revised] PHST- 2021/03/31 00:00 [received] PHST- 2021/07/21 00:00 [accepted] PHST- 2021/09/19 06:00 [pubmed] PHST- 2022/04/07 06:00 [medline] PHST- 2021/09/18 12:13 [entrez] AID - 10.1002/ar.24770 [doi] PST - ppublish SO - Anat Rec (Hoboken). 2021 Nov;304(11):2605-2619. doi: 10.1002/ar.24770. Epub 2021 Sep 18.