Escin shows extended antioxidant, anti-inflammatory, antinecrotic, and anti-apoptotic effects against Con A-induced immune-mediated hepatitis.

Escin suppresses immune cell infiltration and selectively modulates Nrf2/HO-1, TNF-α/JNK, and IL-22/STAT3 signaling pathways in concanavalin A-induced autoimmune hepatitis in mice.

M Elshal, Sara H Hazem

Inflammopharmacology

Dec 1, 2022

Sources

0:00 / 0:00

Sign in to access this feature

Create a free account or sign in to use AI summaries, listen to articles, download PDFs, and save to your library.

98 views

Abstract

The current study aims to investigate the possible protective effect of escin, the active constituent of a natural mixture of triterpene saponin glycoside, against immune-mediated hepatitis driven by concanavalin A (Con A) and to elucidate its possible underlying mechanisms. Adult male mice were administered Con A (15 mg/kg, intravenously) for 8 h. In the treated groups, mice were pretreated with escin daily (10 mg/kg in CMC, orally) for 4 days before Con A intoxication. In addition, escin was administered in a group to examine its effect on normal mice. Our results showed that escin inhibited Con A-induced elevation in liver enzymes (ALT, AST, and LDH) and curbed the Con A-induced hepatocyte necrosis and apoptosis together with abrogating the death pathway, JNK. Coincidentally, escin has shown a reduction in neutrophil, CD4+ T cell, and monocyte infiltration into the liver. In addition, escin modulated the cellular oxidant status by compensating for the Con A-depleted expression of the transcription factor Nrf2 and the stress protein hemeoxygenase-1. These effects were in good agreement with the restraining effect of escin on Con A-instigated overexpression of NF-κB and the pro-inflammatory cytokines TNF-αand IL-17A. Interestingly, Con A provoked the cellular protective pathway IL-22/STAT3, which was revoked by the escin pretreatment. In conclusion, escin shows extended antioxidant, anti-inflammatory, antinecrotic, and anti-apoptotic effects against Con A-induced immune-mediated hepatitis. These effects may collectively be via suppressing immune cell infiltration into the liver and selective modulation of Nrf2/HO-1, TNF-α/NF-κB, TNF-α/JNK, and IL-22/STAT3 signaling pathways.