**1. Introduction**

*Posidonia oceanica* (L.) Delile is a seagrass of extreme ecological importance for the whole marine ecosystem, and it is the only species of the Posidoniaceae family endemic in the Mediterranean Sea [1,2]. Although *P. oceanica* leaves have been used in ancient times in traditional medical practices as a natural remedy for various health disorders, only more recent scientific studies have described its potential benefits for human health, including an anti-diabetic property [3]. For instance, Gokce et al. (2008) demonstrated that *P*. *oceanica* leaf extract has hypoglycemic properties in alloxan-induced diabetic rats [4]. Oral administration of its extract for 15 days dose-dependently decreased blood glucose in diabetic rats [4]. In addition, the hydroalcoholic extract of *P. oceanica* leaves (POE) was able to inhibit the in vitro glucose-induced glycation of human serum albumin [5]. POE has also demonstrated antioxidant and anti-inflammatory properties in in vitro cellular models and in vivo animal models [6,7].

**Citation:** Morresi, C.; Vasarri, M.; Bellachioma, L.; Ferretti, G.; Degl'Innocenti, D.; Bacchetti, T. Glucose Uptake and Oxidative Stress in Caco-2 Cells: Health Benefits from *Posidonia oceanica* (L.) Delile. *Mar. Drugs* **2022**, *20*, 457. https:// doi.org/10.3390/md20070457

Academic Editor: Hideki Kishimura

Received: 20 June 2022 Accepted: 13 July 2022 Published: 14 July 2022

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Overall, the POE biological effects have been related to the synergistic action of its individual constituents. A first UPLC characterization analysis showed that POE consists of 88% phenolic compounds, mostly represented by D-(+)-catechin, and less by gallic acid, ferulic acid, (−)-epicatechin, and chlorogenic acid [8] (Figure 1).

**Figure 1.** Phenolic compounds with relative percentages identified in *P. oceanica* leaf extract (POE) by UPLC analysis [8].

Among the biological properties of dietary polyphenols, growing attention has been devoted to their ability to modulate post-prandial increases in glucose levels and to modulate intestinal integrity and oxidative damage [9–14]. In fact, high post-prandial plasma glucose concentrations are associated with an increased risk of developing type 2 diabetes (T2D) and metabolic syndrome [15]. Intestinal glucose transporters such as sodium glucose co-transporter-1 (SGLT1) and glucose transporter 2 (GLUT2) play a role in glucose homeostasis and represent targets for the management of diabetes [16].

A Caco-2 cell monolayer is one of the most widely used in vitro model of the human intestinal barrier to study absorption [17,18]. This cellular model was used in this study to evaluate the effect of POE on the intestinal glucose uptake and its ability to modulate the levels of glucose transporters (SGLT1 and GLUT2). Furthermore, the intestinal barrier integrity is essential for the metabolic homeostasis. A dysfunction of the intestinal barrier is linked to inflammatory and dysmetabolic conditions, including diabetes [19].

In this study, the effect of POE on intestinal barrier integrity was verified by assessing transepithelial electrical resistance (TEER) across a monolayer of intestinal Caco-2 cells. The effect of POE on the level of Zonula occludens-1 (ZO-1), a protein involved in the regulation of intestinal barrier integrity, was also evaluated.

In addition, the potential protective effect of POE against oxidative stress has been studied in Caco-2 cells using tert-butyl hydroperoxide (TBHP) or chronic exposition to high glucose (HG) levels.

#### **2. Results**
