PMID- 34618611 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20220428 IS - 1532-2513 (Electronic) IS - 0892-3973 (Linking) VI - 43 IP - 6 DP - 2021 Dec TI - Capillin protects against non-alcoholic steatohepatitis through suppressing NLRP3 inflammasome activation and oxidative stress. PG - 778-789 LID - 10.1080/08923973.2021.1984520 [doi] AB - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an extreme form of non-alcoholic fatty liver disease. The present study concentrated on the role of Capillin, a polyacetylene compound isolated from Artemisia capillaris Thunb., in NASH development. MATERIALS AND METHODS: Palmitic acid (PA) was treated with FL83B hepatocytes, and high-fat diet was given to mouse to construct the NASH model in vivo. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were carried out to measure the viability and apoptosis of FL83B hepatocytes. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure the mRNA expressions of infiltration markers (Cd11c, Ccr2, and Ly6c), fibrosis genes (Tgfbeta1, Col1a1, and Timp1), and alpha-smooth muscle actin (alpha-SMA). Western blot, immunofluorescence, and Enzyme-linked immunosorbent assay (ELISA) were implemented to examine the proteins of Caspase-3, Bcl2, Nrf2, HO-1, NLRP3, ASC, and Caspase-1, the ROS level, and oxidative stress markers (MDA, GSH-ST, SOD, and GSH-Px), and the lipid peroxidation level, respectively. Moreover, HE staining was manipulated to observe the histopathological changes in liver tissue. RESULTS: Capillin hampered PA-mediated hepatocytes apoptosis and enhanced cell viability. Furthermore, Capillin suppressed PA-mediated oxidative stress in hepatocytes, promoted Nrf2/HO-1 expression, and repressed NLRP3-ASC-Caspase1 inflammasome. The in vivo studies indicated that Capillin vigorously improves liver fat accumulation, oxidative stress, and liver injury in NASH mice. Mechanistically, Capillin repressed NLRP3-ASC-Caspase1 inflammasome and up-regulated the Nrf2-HO-1 pathway in the liver. CONCLUSION: Capillin ameliorates hepatocyte injury by dampening oxidative stress and repressing NLRP3 inflammasome in NASH mice. FAU - Li, Bin AU - Li B AD - Department of Hepatology, Zaozhuang Hospital of Chinese Medicine, Zaozhuang, Shandong, China. FAU - Wang, Rui AU - Wang R AD - Department of Gastroenterology, Zaozhuang Hospital of Chinese Medicine, Zaozhuang, Shandong, China. FAU - Wang, Lei AU - Wang L AD - Department of Hepatology, Zaozhuang Hospital of Chinese Medicine, Zaozhuang, Shandong, China. FAU - Zhang, Gucheng AU - Zhang G AD - Department of Hepatology, Zaozhuang Hospital of Chinese Medicine, Zaozhuang, Shandong, China. FAU - Zhang, Yang AU - Zhang Y AD - Department of Hepatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China. LA - eng PT - Journal Article DEP - 20211007 PL - England TA - Immunopharmacol Immunotoxicol JT - Immunopharmacology and immunotoxicology JID - 8800150 RN - 0 (Diynes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nlrp3 protein, mouse) RN - 0 (Plant Extracts) RN - 495-74-9 (capillin) SB - IM MH - Animals MH - Diet, High-Fat/adverse effects MH - Diynes/pharmacology/*therapeutic use MH - Dose-Response Relationship, Drug MH - Hepatocytes/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & inhibitors/metabolism MH - Non-alcoholic Fatty Liver Disease/metabolism/*prevention & control MH - Oxidative Stress/*drug effects/physiology MH - Plant Extracts/pharmacology/*therapeutic use OTO - NOTNLM OT - Capillin OT - NLRP3 OT - apoptosis OT - non-alcoholic steatohepatitis OT - oxidative stress EDAT- 2021/10/08 06:00 MHDA- 2022/02/24 06:00 CRDT- 2021/10/07 17:16 PHST- 2021/10/08 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] PHST- 2021/10/07 17:16 [entrez] AID - 10.1080/08923973.2021.1984520 [doi] PST - ppublish SO - Immunopharmacol Immunotoxicol. 2021 Dec;43(6):778-789. doi: 10.1080/08923973.2021.1984520. Epub 2021 Oct 7.