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Juglone Attenuates CCl₄-Induced Hepatic Injury in Mice With Associated Modulation of Oxidative Stress and
Aamir Sohail1, Raza Sufyan1, Muhammad Asim1
1Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan, qau.edu.pk.
Abstract:
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.
Insights
Juglone, a natural compound, shows promise in protecting the liver from carbon tetrachloride (CCl₄)-induced injury by reducing oxidative stress and inflammation. Further studies are needed to confirm its therapeutic potential.
Area of Science:
- Hepatology
- Toxicology
- Natural Product Chemistry
Background:
- Carbon tetrachloride (CCl₄) exposure is a common model for inducing toxic hepatitis, characterized by significant oxidative and inflammatory damage.
- Current therapeutic options for CCl₄-induced liver injury are limited, highlighting the need for novel treatments.
- Juglone, a naphthoquinone from Reynoutria japonica, possesses known antioxidant and anti-inflammatory properties, but its efficacy in a CCl₄ mouse model with detailed gene profiling is underexplored.
Purpose of the Study:
- To investigate the hepatoprotective effects of juglone in a mouse model of CCl₄-induced liver injury.
- To evaluate the impact of juglone on biochemical markers, histological damage, and key molecular pathways including oxidative stress, inflammation, ER stress, apoptosis, and fibrosis.
- To assess juglone's potential as a therapeutic candidate for liver injury.
Main Methods:
- Male C57BL/6 mice were treated with CCl₄ and subsequently with either vehicle, silymarin (a known hepatoprotective agent), or juglone.
- Liver injury was assessed through body weight, serum liver enzymes, lipid profiles, and Hematoxylin and Eosin (H&E) histology.
- Gene expression analysis using RT-qPCR was performed to profile transcripts related to inflammation, pyroptosis, ER stress, autophagy, apoptosis, oxidative stress, and fibrosis.
Main Results:
- CCl₄ exposure led to significant weight loss, elevated liver enzymes, dyslipidemia, and histological liver damage.
- Juglone treatment ameliorated these CCl₄-induced effects, improving biochemical indices and histological outcomes.
- Juglone administration resulted in the downregulation of inflammatory and pyroptosis-related genes (e.g., Il-1β, Il-6, Nlrp3, Gsdmd) and moderated ER stress, autophagy, apoptosis, and profibrotic transcripts (e.g., Acta2, Mmp2, Tgfβ1).
Conclusions:
- Juglone demonstrated significant hepatoprotective effects in the CCl₄-induced mouse liver injury model.
- The protective mechanisms appear to involve the modulation of oxidative stress, inflammation, pyroptosis, ER stress, and apoptosis-related gene expression.
- While these gene-level associations suggest therapeutic potential, further protein-level and functional validation are necessary to confirm juglone's efficacy and establish its role as an antifibrotic agent.
