Caulerpa peltata extract protects against Dextran sodium sulfate-induced acute ulcerative colitis via modulating Nrf2 pathway.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) and poses an increasing public health issue around the world because of the presence of genetic, immunological, and environmental causes. Antioxidants and anti-inflammatory therapy targeting oxidative stress and inflammatory pathways have become the main therapeutic approach with the use of the NRF2 pathway. In this study, the antioxidative, anti-inflammatory and NRF2 regulation activities of ethanolic extract of Caulerpa peltata (CPEE) were investigated using phytochemical screening, in vitro, in vivo, and in silico methods. Firstly, phytochemical screening and in vitro analysis were done in order to determine the phytochemical components and antioxidant potential of the CPEE. The safe dosages of CPEE (1.25-100 µg/mL) were assessed in zebrafish embryotoxicity and morphological, biochemical, and molecular evaluations were conducted in the control mice, DSS-inducing UC mice and UC mice treated with CPEE (100 mg/kg) for seven days. LC-MS molecular docking and molecular dynamics simulation (MDS) were applied for characterizing the bioactive compounds in CPEE and predicting their binding affinities and stability of their interactions with protein targets. Phytochemical screening showed a high amount of flavonoids and tannins with potent antioxidant potential. Safe concentrations were obtained from zebrafish toxicity screening, whereas CPEE treatment in vivo decreased the severity of the disease, maintained levels of antioxidant enzymes, and improved Nrf2, HO-1, and NQO1 expressions; further computational analysis supported stable binding energies of bioactive compounds to Keap1. CPEE decreased oxidative stress, colitis pathology, and exhibited an increase in the enzymatic activity of antioxidants and NRF2-related genes, which confirmed that Caulerpa peltata could be used as a possible source for bioactive compounds for further investigation in UC management.