Capillin protects against non-alcoholic steatohepatitis through suppressing NLRP3 inflammasome activation and oxidative stress.

Abstract

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 (Tgfβ1, Col1a1, and Timp1), and alpha-smooth muscle actin (α-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.

• Authors: Bin Li, Rui Wang, Lei Wang, Gucheng Zhang, Yang Zhang
• Journal: Immunopharmacology and immunotoxicology (Immunopharmacol Immunotoxicol) Vol. 43 Issue 6 Pg. 778-789 (Dec 2021) ISSN: 1532-2513 [Electronic] England
• PMID: 34618611 (Publication Type: Journal Article)

Chemical References

• Diynes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Plant Extracts
• capillin

Topics

• Animals
• Diet, High-Fat (adverse effects)
• Diynes (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Hepatocytes (drug effects, metabolism)
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (antagonists & inhibitors, metabolism)
• Non-alcoholic Fatty Liver Disease (metabolism, prevention & control)
• Oxidative Stress (drug effects, physiology)
• Plant Extracts (pharmacology, therapeutic use)