Caulerpa lentillifera extract alleviates the chronic diquat-induced liver oxidative damage in zebrafish (Danio rerio) in association with Nrf2 and AMPK/mTOR signaling pathway.

This study aimed to investigate the ability and elucidate the mechanisms of Caulerpa lentillifera extract (CLE) in attenuating liver oxidative damage of zebrafish induced by chronic diquat exposure. The components of CLE were analyzed by LC-QTOF-MS/MS, and 34 potential chemicals were revealed. Zebrafish were exposed to diquat and fed CLE-supplemented diets (1 and 2 g/kg) for 60 days. The results showed that CLE treatment ameliorated diquat-exposed liver damage and histological hepatocyte changes. It significantly enhanced the activities and mRNA expression of SOD and CAT, elevated the levels of GSH, and reduced hepatic MDA concentration. CLE effectively suppressed NF-κB phosphorylation, downregulated the expression of pro-inflammatory genes (tnf-α, il-1β and il-6), and upregulated the expression of anti-inflammatory gene (il-10) in diquat-exposed zebrafish livers. The suppression of liver cell apoptosis by CLE in zebrafish was observed, with reduced expression of Caspase3 and decreased Bax/Bcl-2 ratio. CLE inhibited diquat-induced upregulation of autophagy factors Beclin1 and LC3 protein expression levels. Notably, CLE induced hyperactivation of the Nrf2 signaling, evidenced by the enhanced protein expression of Nrf2, HO-1 and NQO1. Meanwhile, CLE treatment reverted the abnormal expression patterns of AMPK, p-AMPK, mTOR and p-mTOR induced by diquat exposure. The overall results suggest that the protection of CLE against liver injury caused by chronic diquat exposure is achieved by improving antioxidative status and suppressing inflammation, cell apoptosis and autophagy. These protective effects are probably attributed to its ability to modulate the Nrf2 and AMPK/mTOR signaling pathways.