**5. Conclusions**

The effect of natural compounds on glucose transporters and their protective effects against oxidative stress have been previously demonstrated in several experimental models. For the first time, this study highlights the ability of POE to reduce glucose transport by lowering the GLUT2 levels, to promote intestinal barrier integrity by modulating ZO-1 levels, and to have a protective antioxidant effect against glucose-induced damage in Caco-2 cells. This is the first study to investigate the behavior of a complex pool of POE phenolic compounds, rather than a single molecule, on differentiated human intestinal Caco-2 cells. We suggest that the biological properties exerted by POE could be related to synergistic effects of its constituents.

In the face of the incessant demand for new alternative natural antioxidants, as well as anti-inflammatory and antidiabetic agents, the cell-safe POE profile makes this phytocomplex an excellent candidate for continuing to investigate the potential use of POE in

the management of chronic diseases, including diabetes, in support of practices described in traditional medicine. Therefore, our results lay the foundation for further in vitro and in vivo studies to verify the antioxidant and antidiabetic role of *P. oceanica*.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/md20070457/s1, Figure S1: Effect of POE on Caco-2 cells viability; Figure S2: Effect of POE on HG-induced intracellular ROS formation; Figure S3: Effect of POE on HG-induced cell toxicity.

**Author Contributions:** Conceptualization, D.D., T.B. and G.F.; methodology, C.M., M.V. and L.B.; writing—original draft preparation, D.D., M.V., T.B. and C.M.; writing—review and editing, D.D., T.B. and G.F.; funding acquisition, D.D., T.B. and G.F. All authors have read and agreed to the published version of the manuscript.

**Funding:** Fondi di Ateneo 2021 D.D., T.B and G.F.

**Institutional Review Board Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** The authors thank the authorized staff of the Interuniversity Center for Marine Biology and Applied Ecology "G. Bacci" (CIBM) (Leghorn, Italy) for kindly providing leaves of *P. oceanica*.

**Conflicts of Interest:** The authors declare no conflict of interest.

## **References**

