Fucoxanthin Protects Against Acute Liver Injury by Inhibiting NOD-Like Receptor Protein 3 Inflammasome-Mediated Pyroptosis Through the Mitogen-Activated Protein Kinases and Nuclear Factor-Kappa B Pathway.

Abstract

Acute liver injury (ALI) is a severe public health problem closely associated with oxidative stress, inflammation, and hepatocyte injury, leading to high mortality. Fucoxanthin (Fx), a marine carotenoid found in brown seaweeds, has various beneficial effects against multiple diseases. However, the potential role of Fx on ALI remains unclear. This study aims to explore the pharmacological potential of Fx in lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced ALI. The therapeutic effect of Fx on ALI was primarily evaluated using a mouse model induced by LPS/D-Gal, focusing on pathological changes, oxidative stress, inflammation, and pyroptosis. Additionally, the effects of Fx on cell pyroptosis and its molecular mechanisms were explored in an in vitro pyroptosis model established by inducing macrophages with LPS/Nigericin. Fx significantly alleviated the LPS/D-Gal-induced histopathological progression and hepatocyte apoptosis, reducing plasma levels of ALT, AST, and LDH. It also obviously decreased hepatic MDA levels while increasing antioxidant enzyme activities and GSH concentration compared to LPS/D-Gal-treated mice. These antioxidant effects were linked to the upregulation of hepatic Nrf-2, HO-1, and GCLC expression. Furthermore, Fx treatment alleviated macrophage accumulation and downregulated the expression of pro-inflammatory factors in the liver. Importantly, Fx administration suppressed NLRP3 inflammasome-dependent canonical pyroptosis both in LPS/D-Gal-treated mice and LPS/Nigericin-stimulated macrophages, potentially mediated by the suppression of MAPKs and NF-κB pathways. These findings suggest that Fx could be an effective strategy to prevent ALI, particularly in cases associated with NLRP3 inflammasome-mediated pyroptosis.

Key Findings

• Fucoxanthin significantly alleviated LPS/D-Gal-induced acute liver injury by reducing hepatocyte apoptosis and improving liver function markers (ALT, AST, LDH).
• Fucoxanthin enhanced antioxidant defenses by increasing hepatic Nrf-2, HO-1, and GCLC expression, antioxidant enzyme activities, and GSH concentration while decreasing MDA levels.
• Fucoxanthin suppressed NLRP3 inflammasome-mediated pyroptosis and downregulated pro-inflammatory factors, potentially via inhibition of MAPKs and NF-κB signaling pathways.

Clinical Significance

Citation

Zheng Yigang, Ying Hanglu, Shi Jiayiet al.. Fucoxanthin Protects Against Acute Liver Injury by Inhibiting NOD-Like Receptor Protein 3 Inflammasome-Mediated Pyroptosis Through the Mitogen-Activated Protein Kinases and Nuclear Factor-Kappa B Pathway. Phytotherapy research : PTR. 2026-May-11.