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Updated: Jun 9, 2025
Induction of Drug-Induced, Autoimmune Hepatitis in BALB/c Mice for the Study of Its Pathogenic Mechanisms
Published on: May 29, 2020
Rhoifolin Attenuates Concanavalin A-Induced Autoimmune Hepatitis in Mice via JAKs/STATs Mediated Immune and Apoptotic
Ge Zhao1,2, Hu Qi2, Minghua Liu3
1Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P. R. China.
Abstract:
Rhoifolin (ROF) exhibits a diverse range of biological activities, encompassing anticancer, hepatoprotective, antidiabetic, antirheumatic, and antiviral properties. However, the specific protective effects and possible mechanisms of the compound against T-cell-mediated autoimmune hepatitis have not been previously elucidated. In the present study, adult male mice were administered Con A (20 mg/kg, intravenously) for 8 h. In the treated groups, mice were pretreated with ROF daily (20 mg/kg and 40 mg/kg, orally) for 7 days before Con A intoxication. The results showed that ROF significantly decreased serum biochemical indices (ALT, AST, ALP, and LDH) and regulated related oxidative stress indicators (MDA, SOD, and GSH), reduced hepatic necrosis areas and immune cells infiltration, inhibited the release of various inflammatory factors (TNF-α, IFN-γ, IL-2, and IL-17), and improved hepatic tissue apoptosis, thereby alleviating hepatic damage induced by Con A. Additionally, we have also confirmed that ROF efficiently inhibited Th1/Th17 cells polarization via modulation of the JAK2/JAK3/STAT1/STAT3 signaling pathways both in vivo and in vitro. Moreover, the molecular mechanism examination also demonstrated that ROF regulated apoptotic cascade signaling through IL-6/JAK2/STAT1/STAT3 controlling BNIP3 activity in primary hepatocytes. These effects were in good agreement with the bioinformatics analysis of ROF treatment for AIH. In conclusion, our findings provide new insights into the potential use of ROF for AIH therapy, which may result from the specific regulation of the T cell subtype polarization and the apoptosis of liver cells via modulation of the JAKs/STATs signaling pathways.
Insights
Rhoifolin (ROF) effectively treats autoimmune hepatitis (AIH) by inhibiting harmful T-cell responses and liver cell apoptosis. This natural compound modulates key signaling pathways, offering a promising therapeutic approach for AIH.
Area of Science:
- Pharmacology
- Immunology
- Hepatology
Background:
- Autoimmune hepatitis (AIH) is a severe liver disease driven by T-cell mediated immune responses.
- Rhoifolin (ROF) is a natural compound with known biological activities, but its effects on AIH are unexplored.
Purpose of the Study:
- To investigate the protective effects and underlying mechanisms of Rhoifolin against T-cell-mediated autoimmune hepatitis in a mouse model.
Main Methods:
- Mice were treated with Rhoifolin before Concanavalin A (Con A) induction of hepatitis.
- Serum biochemical markers, oxidative stress indicators, inflammatory cytokines, and liver histology were analyzed.
- T-cell polarization (Th1/Th17) and apoptosis pathways (JAK/STAT) were examined in vivo and in vitro.
Main Results:
- Rhoifolin significantly reduced liver injury markers, oxidative stress, and inflammatory cytokine release.
- It inhibited immune cell infiltration, hepatic necrosis, and apoptosis.
- ROF suppressed Th1/Th17 cell polarization and modulated JAK/STAT signaling pathways, including IL-6/JAK2/STAT1/STAT3 control of BNIP3.
Conclusions:
- Rhoifolin demonstrates significant hepatoprotective effects against Con A-induced AIH.
- Its therapeutic potential lies in regulating T-cell subtype polarization and liver cell apoptosis via JAK/STAT signaling pathways.
