Hepatoprotection by Garlic Essential Oil Nanoemulsion Through Nrf2-Mediated Antioxidant Response and Inhibition of TLR4/NF-κB/NLRP3 Axis in High-Fat Diet-Fed Rats

Abstract

The present study evaluated the hepatoprotective effects of garlic essential oil nanoemulsion (GEONE) against high-fat diet (HFD)-induced liver injury and metabolic disturbances, compared to crude garlic essential oil (GEO). Sixty rats were randomly divided into six groups: control, GEO-treated (40 mg/kg), GEONE-treated (40 mg/kg), HFD-fed and HFD combined with either GEO or GEONE (40 mg/kg) for 4 weeks following 16 weeks of HFD feeding. GEONE demonstrated superior hepatoprotective activity compared with crude GEO, effectively ameliorating metabolic abnormalities, including dyslipidemia and liver dysfunction, in HFD-fed rats. This effect was associated with attenuation of lipid peroxidation, enhanced activities of antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase and elevated reduced glutathione levels. GEONE also upregulated the expression of key antioxidant genes, Nrf2, HO-1 and NQO1, highlighting activation of cytoprotective pathways. Furthermore, GEONE mitigated HFD-induced inflammation by downregulating the expression of TLR3, TLR4, NF-κB, TNF-α, IL-6 and NLRP3. In addition, co-treatment with GEONE suppressed pro-apoptotic gene expression (Bax and caspase-3) while enhancing anti-apoptotic Bcl-2 levels, indicating protection against hepatocyte apoptosis. Histopathological and ultrastructural analyses confirmed the previous biochemical findings. Overall, GEONE provides effective protection against HFD-induced liver injury by activating the Nrf2/HO-1 antioxidant defence system and suppressing the TLR4/NF-κB/NLRP3 inflammatory cascade.