Hypnea musciformis Seaweed Extract Protected Human Mesenchymal Stem Cells From Oxidative Stress Through NRF2 Activation

ABSTRACT Previous studies have shown that Hypnea musciformis seaweed extracts (HMEs) possess antioxidant properties, but the molecular mechanisms accounting for this activity are not known. Thus, the present study investigated the molecular mechanisms through which HME exerted its antioxidant activity in human mesenchymal stem cells (WJ‐MSCs). After the isolation of HME, its chemical composition was analyzed with gas chromatography mass spectrometry, indicating that it contained amino acids, organic acids, organic amides, sugar alcohols, saturated fatty acids, hydrogenated diterpene alcohols, and other organic compounds. Afterward, HME was shown in vitro to scavenge DPPH·, ABTS·+, ·OH, and O2·− radicals, possess reducing activity, and protect from ROO·‐induced DNA strand breakage. Finally, the results showed that HME treatment of WJ‐MSCs prevented H2O2‐induced oxidative stress by decreasing lipid peroxidation, protein oxidation, reactive oxygen species levels, and DNA damage and by increasing glutathione levels. Moreover, our findings showed for the first time that HME's antioxidant activity in WJ‐MSCs was mediated through the activation of NRF2, which upregulated the expression of the antioxidant proteins GCLC, GSR, HMOX1, SOD1, TXN, and GPX1. These results provide new insights into H. musciformis' antioxidant properties, which could help substantially its use as a food supplement or for developing biofunctional foods. Extract of Hypnea musciformis seaweed collected from the Mediterranean Sea contained polyphenols, flavonoids, proteins, amino acids, organic acids, organic amides, sugar alcohols, saturated fatty acids, fatty acid esters, hydrogenated diterpene alcohols, and other organic compounds. HME treatment of human mesenchymal stem cells (WJ‐MSCs) prevented H2O2‐induced oxidative stress by decreasing lipid peroxidation, protein oxidation, ROS levels, and DNA damage and by increasing glutathione. HME's antioxidant activity was mediated through activation of NRF2, which upregulated the expression of the antioxidant proteins GCLC, GSR, HMOX1, SOD1, TXN, and GPX1. These results give new insight for Hypnea musciformis antioxidant properties and its possible use as food supplement or for developing biofunctional foods preventing from oxidative stress‐induced pathologies.