Protective effects of carnosic acid against LPS/D-GalN–induced acute liver injury via modulation of inflammatory and oxidative stress pathways

J. Amjath Khan; K. Abdul Hakeem; Shabana Mateen; V.D. Seshadri; Arun Kumar Ramu; Bakrudeen Ali Ahmed Abdul

doi:10.55779/nsb18212831

Authors

J. Amjath Khan PRIST Deemed University, Research Development Cell, Department of Biochemistry and Biotechnology, Thanjavur 613403, Tamil Nadu (IN)
K. Abdul Hakeem PRIST Deemed University, Research Development Cell, Department of Microbiology, Thanjavur, Tamil Nadu (IN) https://orcid.org/0000-0002-3942-4084
Shabana Mateen PRIST Deemed University, Research Development Cell, Department of Biochemistry and Biotechnology, Thanjavur 613403, Tamil Nadu (IN) https://orcid.org/0000-0001-8949-2803
V.D. Seshadri Prince Sattam Bin Abdul Aziz University, College of Pharmacy, Department of Pharmacology and Toxicology, Al-Kharj (SA) https://orcid.org/0000-0001-6822-9491
Arun Kumar Ramu PRIST Deemed University, Research Development Cell, Department of Biochemistry and Biotechnology, Thanjavur 613403, Tamil Nadu (IN) https://orcid.org/0000-0002-2365-2920
Bakrudeen Ali Ahmed Abdul PRIST Deemed University, Research Development Cell, Department of Biochemistry and Biotechnology, Thanjavur 613403, Tamil Nadu (IN) https://orcid.org/0000-0002-8087-5899

DOI:

https://doi.org/10.55779/nsb18212831

Keywords:

acute liver injury, carnosic acid, LPS/D-GalN, oxidative stress, TLR4/NF-κB signaling

Abstract

Acute liver failure is often associated with excessive inflammation and oxidative stress. The combination of lipopolysaccharide (LPS) and D-galactosamine (D-GalN) is widely used to induce experimental liver injury that mimics fulminant hepatitis. Carnosic acid, a natural polyphenolic compound derived from Rosmarinus officinalis, exhibits notable anti-inflammatory and antioxidant properties. The present study investigated the protective effects of carnosic acid against LPS/D-GalN–induced acute liver injury in rats. Adult Wistar rats were pretreated with carnosic acid prior to a single intraperitoneal injection of LPS/D-GalN. After 24 h, blood and liver tissues were collected for biochemical, molecular, and histological analyses. Serum liver function markers (ALT, AST, ALP, and bilirubin) and oxidative stress parameters (MDA, GSH, SOD, and CAT) were evaluated. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) were quantified, and the expression of key inflammatory genes (TLR4, MyD88, NF-κB p65, COX-2, and iNOS) was assessed using RT-qPCR. Histopathological examination was performed to evaluate tissue architecture, and molecular docking analysis was conducted to explore ligand–protein interactions. Pretreatment with carnosic acid significantly improved liver function markers, reduced oxidative stress, and suppressed proinflammatory cytokine production. Gene expression analysis and docking results further indicated modulation of the TLR4/NF-κB signaling pathway. In conclusion, carnosic acid exerts marked hepatoprotective effects against LPS/D-GalN–induced acute liver injury, likely through combined antioxidant and anti-inflammatory mechanisms.

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