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Jingfang Granule Protects Against Concanavalin-A-Induced Immune Hepatitis in Mice Through Regulating Tricarboxylic Acid Cycle
- Publication Year :
- 2022
- Publisher :
- Research Square Platform LLC, 2022.
-
Abstract
- Background Autoimmune hepatitis (AIH) is an autoimmune mediated inflammatory disease that causes serious economic burden to mankind. Previous studies reported that Jingfang Granules (JFG) had an anti-inflammatory effect. However, there are few studies of JFG on AIH. The aim of the study was to investigate the therapeutic effect of JFG on AIH and its mechanisms of action. Methods The animal model of AIH was constructed by intravenous injection of Concanavalin A (Con A). JFG treatment was given by intragastric gavage (ig) after an hour later of injected Con A. Serum and liver tissues were collected after 24 h treatment. Mortality, histology, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in serum were to evaluate therapeutic effect of JFG. The apoptosis of hepatocyte was detected by terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling assay (TUNEL). The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2 Associated X (Bax), Cleaved-Caspase 3, Toll-like receptor 4 (TLR4)/nuclear factor kappa B p65 (NF-κB), Mitogen activated protein kinase (MAPK) pathways associated proteins, CS, IDH1, ACLY, SUCLG1, and SUCLA2 were measured by western blot. The inflammatory cytokines interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), tumor necrosis factor (TNF)-α, interferon (IFN)-γ and anti-inflammatory cytokine interleukin-10 (IL-10) were checked by ELISA. The possible target mechanism of JFG in the treatment of AIH was explored by proteomics and metabolomics. Results The results showed that JFG substantially alleviated Con A-mediated hepatitis in mice, which was shown by increased survival rates, decreased of liver injury, aminotransferase, hepatocyte necrosis, and apoptosis. JFG could also regulate the production of inflammatory factors (IL-1β, IL-4, IL-6, TNF-α, IFN-γ and IL-10) by reduced the activation of TLR4/NF-κB and MAPK pathways. In addition, it was found that JFG could inhibit the inflammatory pathway by regulating tricarboxylic acid (TCA) cycle activity. Conclusions These results suggested that JFG played a therapeutic role in Con A-induced AIH by inhibiting liver injury, apoptosis, and inhibiting inflammatory pathway by regulating TCA cycle.
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........796836adb9548ffee19b126fb8784876