Enhancement of the Anti-Inflammatory Effect of Zingerone Using the Galactosylated Chitosan Nano Formula Against CCl4-Induced Hepatic Fibrosis: An In Vivo Study

Without anti-inflammatory treatment, liver fibrosis can result in severe, intractable complications that are potentially fatal. This study was designed to evaluate the anti-inflammatory effects of prepared zingerone-loaded galactose chitosan nanoparticles (Zing-GCSNPs) on carbon tetrachloride (CCl4)-induced liver fibrosis in vivo. Zing-GCSNPs were produced via the use of chitosan polymers in a modified ionic gelation process. The formula was tested via XRD, FTIR, HRTEM, and dynamic light scattering. Additionally, we examined the release of zingerone, its cytotoxicity to HepG2 cells, and its antifibrotic efficacy in rats. Zing-GCSNPs were formed with an entrapment effectiveness of 66.33%, a mean zeta sizer distribution of 179.6 nm, and a potential of -36.7 mV. The percentage of the cumulative release of free zingerone was approximately 98.8% after 12 h, whereas the Zing-GCSNPs showed a sustained release profile with a gradual step, culminating in a release percentage of 66.4% at the end of the experiment. The IC50 of the investigated formula was 171.35 µg/ml, and it was more efficient at ameliorating the alterations in biochemical liver function, inflammation state, oxidative stress markers and apoptotic markers induced by CCl4 than were free zingerone and GCSNPs. Additionally, Zing-GCSNPs restored the normal hepatocyte configuration, suggesting a hepatoprotective effect and an anti-inflammatory effect of the prepared nanoformula. The anti-inflammatory efficacy of zingerone was improved when it was infused with a galactose chitosan nanoformula, and it improved liver function parameters, oxidative stress markers, and the inflammatory state, allowing it to reverse hepatic architectural distortion and mitigate the severity of fibrosis.