Olive and Linseed Oil Blend‐Based Nanoemulsions Fortified With Ginger Extract Nutraceutical: Mitigating Liver Fibrosis Induced by Carbon Tetrachloride by Regulating Oxidative Stress and TGF‐β/MMP9 Signaling Pathway in Rats

Abstract

Liver fibrosis is a significant contributor to global morbidity and mortality, making the identification of non‐toxic natural therapies to slow its progression essential. This study evaluated the anti‐fibrotic potential of a nutraceutical blend comprising extra virgin olive oil, linseed oil, and ginger extract, formulated in both emulsion and nanoemulsion forms, using a rat model of liver fibrosis. Nanoemulsions were prepared using the ultrasonication technique, and their particle size and stability were analyzed via the DLS method. Twenty‐four male albino rats were divided into four groups: normal control, CCl4‐treated, oil emulsion‐treated, and nanoemulsion‐treated. Liver fibrosis was induced by oral administration of carbon tetrachloride (CCl4), while the emulsions were administered daily alongside CCl4 for four weeks. Liver function indices, oxidative stress biomarkers, and gene expressions were assessed, along with histopathological and immunohistochemical analyses. The results revealed that both emulsions significantly improved liver function, enhanced antioxidant capacity, and reduced lipid peroxidation. They downregulated pro‐fibrogenic markers (TGF‐β1, TIMP‐1) and upregulated anti‐fibrogenic markers (MMP9, HGF), leading to a reduction in liver fibrosis. The nanoemulsion exhibited superior efficacy compared to the emulsion. These findings demonstrate that the nutraceutical blend, particularly in nanoemulsion form, effectively attenuated liver fibrosis and improved hepatic health markers. This underscores its potential as a natural therapy for liver fibrosis and related conditions, emphasizing its nutritional value in supporting liver health.