**1. Introduction**

Reactive oxygen species (ROS) are substances produced by human cells and tissues during normal physiological metabolism. Under normal circumstances, the body's antioxidant defense mechanisms play a role in the body's oxidative balance. However, when a large amount of ROS accumulates in the human body, it will cause oxidative imbalance and further aggravate the damage to the body [1]. The accumulation of ROS in the organism comes not only from the damage to the organism itself, but also from environmental pollution, radiation, and abuse of chemical products, which can cause the increase in ROS. Therefore, maintaining a balance of reactive oxygen species and antioxidant systems in the body is crucial to health. D-Galactose (D-gal) is a substance naturally occurring in the human body, but high concentrations of galactose will produce a large number of reactive oxygen species, leading to the aging of multiple tissues in the body and the occurrence of age-related immune decline; degenerative nervous system disorders; and damage to

**Citation:** Yang, Q.; Jiang, Y.; Fu, S.; Shen, Z.; Zong, W.; Xia, Z.; Zhan, Z.; Jiang, X. Protective Effects of *Ulva lactuca* Polysaccharide Extract on Oxidative Stress and Kidney Injury Induced by D-Galactose in Mice. *Mar. Drugs* **2021**, *19*, 539. https://doi.org/ 10.3390/md19100539

Academic Editors: Donatella Degl'Innocenti and Marzia Vasarri

Received: 26 August 2021 Accepted: 21 September 2021 Published: 25 September 2021

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pancreas, kidney and other organs [2]. Therefore, the D-gal mouse model has become a widely used aging model.

Natural products with antioxidant activity have received extensive attention due to their good biological safety. With the attention to marine resources and the development of marine natural products, a variety of products that are raw materials with seaweed polysaccharides are gradually entering people's line of sight, and the antioxidant effect of algae polysaccharides has been confirmed [3]. It has been shown that fucoidans from brown algae can not only reduce the production of reactive oxygen species, but also increase the level of glutathione (GSH) and catalase (CAT) activity and reduce cytotoxicity [4,5]. *Ulva lactuca* is a kind of green algae in coastal areas of China. As a traditional Chinese medicine, it has good healthcare function. Ulvan is a water-soluble polysaccharide existing in the cell wall of *Ulva*, accounting for 8–29% of the dry weight [6]. It is a kind of sulfated heteropolysaccharide, which mainly includes sulfated rhamnose (Rha), xylose (Xyl), and uronic acid (glucuronic acid (GlcA) and iduronic acid (IdoA)); the structures of the main disaccharide repeating unit are [β-D-GlcpA-(1 → 4)-α-L-Rhap3s] and [α-L-IdopA-(1 → 4)-α-L-Rhap3s] [7]. Li et al. [8] found that the ulvan had a good scavenging ability against superoxide free radicals and DPPH free radicals in a concentration-dependent manner. Marlene Godardd et al. [9] reported that *U. lactuca* polysaccharide could significantly increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and inhibit the production of lipid peroxidation and superoxide anion. In addition, ulvan with high sulfate content has obvious antioxidant ability and lipid-lowering activity [10]. Therefore, using ulvan as the raw material to develop medicine or food that can remove excess free radicals in the body is not only safe in composition but also effective and has a broad prospect.

In this study, *Ulva lactuca* polysaccharide extract (UPE) was obtained from *U. lactuca*, and D-gal was used to induce oxidative stress in mice to study the effects of UPE on oxidative stress and inflammation in mice. Hematoxylin and eosin staining and immunohistochemistry were used to explore the tissue damage and cell apoptosis in mice.
