**Fucoidan from** *Ascophyllum nodosum* **Suppresses Postprandial Hyperglycemia by Inhibiting Na** + /**Glucose Cotransporter 1 Activity**

**Xindi Shan 1,2,**†**, Xueliang Wang 1,2,**†**, Hao Jiang 1,2, Chao Cai 1,2, Jiejie Hao 1,2,\* and Guangli Yu 1,2,\***


Received: 13 August 2020; Accepted: 19 September 2020; Published: 22 September 2020

**Abstract:** We previously demonstrated that fucoidan with a type II structure inhibited postprandial hyperglycemia by suppressing glucose uptake, but the mechanism remains elusive. Here, we aimed to assess whether the e ffect of glucose absorption inhibition was related to the basic structure of fucoidans and preliminarily clarified the underlying mechanism. Fucoidans with type II structure and type I structure were prepared from *Ascophyllum nodosum* (AnF) or *Laminaria japonica* (LjF) and *Kjellmaniella crassifolia* (KcF), respectively. The e ffects of various fucoidans on suppressing postprandial hyperglycemia were investigated using in vitro (Caco-2 monolayer model), semi-in vivo (everted gu<sup>t</sup> sac model), and in vivo (oral glucose tolerance test, OGTT) assays. The results showed that only AnF with a type II structure, but not LjF or KcF with type I structure, could inhibit the glucose transport in the Caco-2 monolayer and everted gu<sup>t</sup> sac models. A similar result was seen in the OGTT of Kunming mice and leptin receptor-deficient (db/db) mice, where only AnF could e ffectively inhibit glucose transport into the bloodstream. Furthermore, AnF (400 mg/kg/d) treatment decreased the fasting blood glucose, HbA1c, and fasting insulin levels, while increasing the serum glucagon-like peptide-1 (GLP-1) level in obese leptin receptor-deficient (db/db) mice. Furthermore, surface plasmon resonance (SPR) analysis revealed the specific binding of AnF to Na+/glucose cotransporter 1 (SGLT1), which indicated the e ffect of AnF on postprandial hyperglycemia could be due to its suppression on SGLT1 activity. Taken together, this study suggests that AnF with a type II structure can be a promising candidate for hyperglycemia treatment.

**Keywords:** fucoidan from *Ascophyllum nodosum*; postprandial hyperglycemia; in vitro and in vivo evaluation; SGLT1
