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• Quercetin compounds can attenuate liver injury induced by AA, reduce venous congestion and inflammatory infiltration.
• Quercetin compounds attenuate AA induced liver oxidative stress by affecting ROS level.
• Akt/mTOR signaling pathway is activated to affect LC3 transformation and autophagy formation.
• Reverse the activity of caspase-9 and Caspase-3 and increase the ratio of Bax/Bcl-2.
• reverse the activation of IRE1-xbp1 pathway and increase the expression of CHOP protein.
Quercetin compounds have antioxidant, anti-inflammatory and anticancer pharmacological functions. Longterm exposure to acrylamide (AA) can cause liver injury and endanger human health. However, whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear. Here, we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro. In vivo studies found that quercetin-like compounds protect against AA-induced liver injury by reducing oxidative stress levels, activating the Akt/mTOR signaling pathway to attenuate autophagy, and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis. In vitro studies found that quercetin compounds protected HepG2 cells from AA by attenuating the activation of AA-induced autophagy, lowering reactive oxygen species (ROS) levels by exerting antioxidant effects and thus attenuating oxidative stress, increasing mitochondrial membrane potential (MMP), and improving apoptosis-related proteins, thus attenuating AA-induced apoptosis. Furthermore, the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity, with quercetin showing the best protective capacity due to its strongest antioxidant activity. In conclusion, quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress, autophagy and apoptosis, and their protective capacity correlates with antioxidant activity.
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