biostudies-literatureUnknown20(3)Dong Y<h4>Background</h4>Acetaminophen (APAP) can be used for pain relief and fever alleviation, the overdose of which, however, may lead to the accumulation of N-acetyl-p-benzoquinone imine (NAPQI), inducing oxidative stress and liver damage. The natural compound SMND-309 has been shown to have hepatoprotective effects and potential antioxidant activity. However, its ability to alleviate acetaminophen-induced acute liver injury (AILI) has not been elucidated.<h4>Objective</h4>To explore the protective effect of the natural compound SMND-309 against AILI and the potential mechanism.<h4>Methods</h4>The AILI model was established using a mouse model and HepG2 cells for pathological evaluation and biochemical assays of mouse liver tissues to assess the level of liver injury. The effects of SMND-309PloS onee0310879https://www.ebi.ac.uk/biostudies/studies/S-EPMC11957308biostudies-literatureSMND-309 activates Nrf2 signaling to alleviate acetaminophen-induced hepatotoxicity and oxidative stress.PMC11957308Dong YLi QYan RShi ZWang JWang LLiu WLi NJiang YQiu YDing WJia RXu SfalseSMND-309 activates Nrf2 signaling to alleviate acetaminophen-induced hepatotoxicity and oxidative stress.<h4>Background</h4>Acetaminophen (APAP) can be used for pain relief and fever alleviation, the overdose of which, however, may lead to the accumulation of N-acetyl-p-benzoquinone imine (NAPQI), inducing oxidative stress and liver damage. The natural compound SMND-309 has been shown to have hepatoprotective effects and potential antioxidant activity. However, its ability to alleviate acetaminophen-induced acute liver injury (AILI) has not been elucidated.<h4>Objective</h4>To explore the protective effect of the natural compound SMND-309 against AILI and the potential mechanism.<h4>Methods</h4>The AILI model was established using a mouse model and HepG2 cells for pathological evaluation and biochemical assays of mouse liver tissues to assess the level of liver injury. The effects of SMND-3092025-01-01T00:00:00Z20252026-06-01T19:10:30.569Z2026-05-19T03:07:12.329ZS-EPMC119573084016343010.1371/journal.pone.0310879