1H-NMR metabolomics reveals that astaxanthin nanoemulsion reverses liver damage by promoting restoration of energy and lipid metabolism.

The therapeutic potential of astaxanthin is limited by its poor water solubility, which restricts its bioavailability and clinical translation. To overcome this limitation, an astaxanthin nanoemulsion (NEAX) was developed to enhance its oral delivery and hepatic targeting. The efficacy was evaluated in a hepatotoxicity model using physiological parameters and 1H-NMR serum metabolomics analyzed through Orthogonal Partial Least-Squares Discrimination Analysis (OPLS-DA). Wistar rats with thioacetamide-induced liver injury (150 mg/kg, i.p., twice weekly × 6 weeks) received oral astaxanthin (15 mg/kg) for 4 weeks as oil suspension (AX) or lecithin-based NEAX. Both treatments reduced serum transaminases, but only NEAX significantly increased hepatic antioxidant activity. The metabolomics analysis of biomarkers associated with liver damage and regeneration showed changes promoted by AX and NEAX. It also revealed that NEAX reversed liver damage by promoting restoration of metabolites involved in energy and lipid metabolism while limiting fatty acid β-oxidation and increasing metabolites associated with phospholipid insertion in the cellular membrane during liver regeneration, previously not reported for astaxanthin. These findings demonstrate that nanoemulsion delivery systems enhance the therapeutic effects of AX, advancing the development of hepatoprotective therapies based on nanoformulation strategies. They also highlight the potential of metabolomics to understand the mechanisms of hepatic damage and its treatment.