Abstract
Sargassum serratifolium C. Agardh (Phaeophyceae, Fucales) is a marine brown alga that belongs to the family Sargassaceae. It is widely distributed throughout coastal areas of Korea and Japan. S. serratifolium has been found to contain high concentrations of plastoquinones, which have strong anti-cancer, anti-inflammatory, antioxidant, and neuroprotective activity. This study aims to investigate the anti-diabetic activity of S. serratifolium and its major constituents through inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, and ONOO−-mediated albumin nitration. S. serratifolium ethanolic extract and fractions exhibited broad PTP1B and α-glucosidase inhibitory activity (IC50, 1.83~7.04 and 3.16~24.16 µg/mL for PTP1B and α-glucosidase, respectively). In an attempt to identify bioactive compounds, three plastoquinones (sargahydroquinoic acid, sargachromenol and sargaquinoic acid) were isolated from the active n-hexane fraction of S. serratifolium. All three plastoquinones exhibited dose-dependent inhibitory activity against PTP1B in the IC50 range of 5.14–14.15 µM, while sargachromenol and sargaquinoic acid showed dose-dependent inhibitory activity against α-glucosidase (IC50 42.41 ± 3.09 and 96.17 ± 3.48 µM, respectively). In the kinetic study of PTP1B enzyme inhibition, sargahydroquinoic acid and sargaquinoic acid led to mixed-type inhibition, whereas sargachromenol displayed noncompetitive-type inhibition. Moreover, plastoquinones dose-dependently inhibited ONOO−-mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of type 2 diabetes.
Highlights
Diabetes mellitus (DM) has become a major growing public health problem worldwide
Plastoquinones dose-dependently inhibited ONOO− -mediated albumin nitration. Docking simulations of these plastoquinones demonstrated negative binding energies and close proximity to residues in the binding pocket of Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase, indicating that these plastoquinones have high affinity and tight binding capacity towards the active site of the enzymes. These results demonstrate that S. serratifolium and its major plastoquinones may have the potential as functional food ingredients for the prevention and treatment of type 2 diabetes
In order to evaluate the anti-diabetic potential of S. serratifolium, the EtOH extract and its fractions were tested via in vitro α-glucosidase and PTP1B inhibitory assays
Summary
DM is a chronic disease that arises when the pancreas does not produce enough insulin or when the body cannot effectively use it, resulting in hyperglycemia. Type II DM (non-insulin-dependent diabetes) results from the ineffective use of insulin due to excess body weight, physical inactivity, and genetic susceptibility [1]. Mar. Drugs 2017, 15, 368 which controls both insulin and the leptin signaling pathway. The insulin-signaling pathway is a key pathway responsible for blood glucose regulation. PTP1B catalyzes the de-phosphorylation of activated insulin receptors, resulting in down-regulation of insulin signaling [4,5]. It has been reported that PTP1B knocked-out mice have resulted in enhanced insulin sensitivity, which indicate that PTP1B is the major player in the modulation of insulin sensitivity [6].
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