Juglone Attenuates CCl₄-Induced Hepatic Injury in Mice With Associated Modulation of Oxidative Stress and Inflammasome-Related mRNA Expression.

Carbon tetrachloride-induced liver injury is a well-established model of toxic hepatitis, characterized by marked oxidative and inflammatory damage. It remains a relevant experimental system because broadly effective therapeutic options are still limited. Juglone, a natural naphthoquinone derived from Reynoutria japonica, has demonstrated antioxidant and anti-inflammatory potential. However, mouse evidence combining standard liver injury measures with stress- and cell-death gene profiling remains limited. Building on juglone studies in injury and fibrosis, we tested juglone in a CCl4 model. Male C57BL/6 mice were assigned to normal, vehicle, CCl₄, silymarin (200 mg/kg), and juglone (8 mg/kg) groups, and CCl₄ (in corn oil) was administered intraperitoneally. Endpoints included body weight, serum liver enzymes and lipid profile, H&E histology, and RT-qPCR panels for inflammatory, pyroptosis-associated, ER stress and autophagy-linked, apoptotic, oxidative-stress, and profibrotic transcripts. CCl₄ exposure was associated with weight loss, enzyme elevation, dyslipidemia, and architectural disruption, whereas juglone treatment was associated with improved biochemical indices and histology alongside coordinated downregulation of inflammatory/pyroptosis-related transcripts (including Il-1β, Il-6, Nlrp3, and Gsdmd) and moderation of ER stress/autophagy and apoptosis-linked transcripts, with downregulation of profibrotic transcripts (Acta2, Mmp2, and Tgfβ1). In this mouse CCl₄ model, juglone treatment was associated with reduced serum and tissue injury signatures together with changes in stress and inflammation-linked transcriptional programs. Because the molecular findings are primarily based on RT-qPCR, these results are best interpreted as gene-level associations compatible with modulation of oxidative stress, inflammasome- and pyroptosis-related mRNA expression, ER stress responses, apoptosis-linked transcripts, and remodeling-associated transcripts, rather than as confirmed pathway inhibition or established antifibrotic activity. These data support juglone as a hepatoprotective candidate and identify protein-level and functional validation as important next steps.