Hepatoprotective effects of pentadecanoic acid-rich microalgae Melosira nummuloides in a high-fat diet-induced mouse model of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), which is closely associated with obesity and metabolic syndrome, represents a major global health concern with limited therapeutic options. In this study, we evaluated the hepatoprotective effects of Melosira nummuloides ethanol extract (ME) and its major constituent, pentadecanoic acid (PDA), in a high-fat diet (HFD) mouse model. ME and PDA administration increased p-AMPK/AMPK and PPARα while suppressing SREBP-1, thereby restoring hepatic lipid metabolism. Moreover, ME and PDA attenuated inflammation by downregulating NFκB and NLRP3, leading to reduced hepatic levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). They also enhanced antioxidant defenses via activation of the ERK/HO-1 pathway and upregulation of antioxidant enzymes (NQO1, SOD, GPX4), thereby mitigating hepatic oxidative stress. Collectively, these findings demonstrate that ME and its major constituent, PDA, exert hepatoprotective effects against NAFLD and may serve as functional dietary interventions for managing metabolic liver disorders. • ME alleviates hepatic steatosis in HFD-induced NAFLD mice. • PDA, a key ME component, activates AMPK and enhances fatty acid oxidation. • ME and PDA suppress NFκB/NLRP3 signaling and reduce inflammation in the liver. • ME and PDA mitigate oxidative stress by upregulating antioxidant genes.