Integrated serum and liver metabolomics decipher the hepatoprotective mechanisms of mangiferin sodium salt through modulating alcohol metabolism on alcoholic liver disease

Abstract

The natural xanthone derivative mangiferin (MG) has recently been identified as possessing hepatoprotective potential. Yet, its natural form suffers from low bioavailability, and until now, the effects of a more bioavailable mangiferin sodium salt derivative (MG-Na) on alcohol-induced liver damage had not been evaluated. In this study, we administered MG-Na to rats during alcohol consumption and conducted pharmacological and metabolomic research to assess its impact on liver metabolism, oxidative stress, and inflammation. Our results show that MG-Na effectively mitigated alcohol-induced liver injury, diminishing oxidative stress, inflammation and lipid accumulation. These outcomes may be attributed to the modulation of alcohol oxidation metabolism, activation of the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway as well as the AMPK pathway, and suppression of both the arachidonic acid pathway and the nuclear factor kappa B (NF-κB) inflammation pathway. Consequently, our research provides preliminary evidence that MG-Na displays promising anti-inflammatory and antioxidant properties for intervening in alcoholic liver disease (ALD), suggesting a viable path for ALD mitigation.