| Summary: | Phlorotannins are phenolic compounds existing in large amounts in Phaeophyta, with this amount differing according to the season and collection area. There are many pharmacological properties of phlorotannins, such as being antioxidant, antidiabetic, and anti-cancer. In this work, phlorotannins from the Phaeophyta <i>Sargassum linifolium</i> were extracted, characterized, and identified, for use as an antioxidant and an anti-diabetic in a streptozotocin-induced diabetes rat model. Phlorotanins were characterized using ultraviolet (UV) and Fourier transform infrared (FT-IR) analysis, dimethoxy benzaldehyde assay (DMBA), and Folin–Ciocalteu assays. Groups of rats were tested as follows: normal control (negative control) (G1), normal rats treated with 60 mg/kg body weight of phlorotannins (G2), positive control diabetic rats injected with one dose of streptozotocin (G3), and a diabetic group treated with phlorotannins at 60 mg kg<sup>−1</sup> body weight (G4). The biochemical parameters were determined after 4 weeks of treatment. The results demonstrated that the extracted compound was a phlorotannin, which had antioxidant properties. An <i>in vivo</i> study confirmed that the glucose and insulin levels in G4 were relatively similar to those in the normal control G1. The glucosidase, alpha-amylase, glutathione, and catalase levels were 0.11 ± 0.097, 420.5 ± 13, 11.27 ± 3.3, and 8.01 ± 1.31 µmol/min/g in G1, and 0.04 ± 0.016, 184.75 ± 55.24, 12.78 ± 2.1, and 11.28 ± 1.74 µmol/min/g) in G4, respectively. There were no side effects in the kidney function of both G2 and G4, and the levels of cholesterol and triglyceride were also normal. The results demonstrated that phlorotannins have antioxidant properties <i>in vivo</i> and that the diabetic rats had an activated AMPK expression. According to the histological analysis, phlorotannins improved the islet size and reversed necrotic and fibrotic alterations in the pancreas. The results of the present study suggest the use of phlorotannins derived from <i>Sargassum linifolium</i> as an antioxidant and anti-diabetic for an <i>in vivo</i> study. They could be used in developing medicinal preparations for treating diabetes and its related symptoms.
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