Table 4.
Effect of marine phenolics in the prevention of type 2 diabetes mellitus (T2DM).
| Compounds/Marine Source | Test Model | Outcome | Ref. |
|---|---|---|---|
| Five isolated phlorotannins from E. cava (fucodiphloroethol G, dieckol, 6,6′-bieckol, 7-phloroeckol, phlorofucofuroeckol-A) | In vitro assay: α-glucosidase and α-amylase inhibitory activity | Inhibition of α-glucosidase (IC50 values ranged from 10.8 μM for dieckol to 49.5 μM for 7-phloroeckol) and α-amylase (IC50 values ranged from 125 μM for dieckol to <500 μM for the rest of compounds, except 7-phloroeckol with a value of 250 μM) activities |
[165] |
| Methanolic extract isolated from A. nodosum rich in phlorotannins | In vitro assay: α-glucosidase and α-amylase inhibitory activity | Inhibition of α- glucosidase (IC50~20 μg/mL GAE) and α-amylase (IC50~0.1 μg/mL GAE) activities | [166] |
| Cold aqueous and ethanolic extracts of A. nodosum and F. vesiculosus rich in phlorotannins | In vitro assay: α-glucosidase and α-amylase inhibitory activity | Inhibition of α- glucosidase (IC50~0.32–0.50 μg/mL GAE for F. vesiculosus) and α-amylase (IC50~44.7–53.6 μg/mL GAE for A. nodosum) activities | [167] |
| Methanolic extract from Alaria marginata and Fucus distichus rich in phlorotannins | In vitro assay: α-glucosidase and α-amylase inhibitory activity | Inhibition of α- glucosidase (IC50~0.89 μg/mL) and α-amylase (IC50~13.9 μg/mL) activities | [168] |
| Polyphenol-rich extracts from L. trabeculate | In vitro assay: α-glucosidase and lipase activity | Inhibition of α-glucosidase and lipase activities (IC50 < 0.25 mg/mL) | [103] |
| Crude extract and semi-purified phlorotannins from F. vesiculosus composed by fucols, fucophlorethols, fuhalols and several other phlorotannin derivatives | In vitro assay: α-glucosidase, α-amylase and pancreatic lipase inhibitory activity | Inhibition of α-amylase (IC50~28.8–2.8 μg/mL), α-glucosidase (IC50~4.5–0.82 μg/mL) and pancreatic lipase (IC50~45.9–19.0 μg/mL) activities | [120] |
| Phlorotannin derivatives from E. cava | In vitro assay: α-glucosidase inhibitory activity | Inhibition of α-glucosidase activity (IC50~2.3–59.8 μM) Kinetic parameters of receptor–ligand binding |
[163] |
| Phlorotannin-targeted extracts from four edible Fucus species (F. guiryi, F. serratus, F. spiralis and F. vesiculosus) | In vitro assay: α-glucosidase and α-amylase inhibitory activity | Inhibition of α-glucosidase (IC50~2.48–4.77 μg/mL), α-amylase (IC50~23.31–253.31 μg/mL) and xanthine oxidase (IC50~157.66–800.08 μg/mL) activities | [8] |
| Marine-derived bromophenol compound (3,4-dibromo-5-(2-bromo-3,4-dihydroxy-6-(ethoxymethyl)benzyl)benzene-1,2-diol) isolated from Rhodomela confervoides | In vitro: insulin resistant C2C12 cells treated with bromophenol (0.1–0.5 μM for phenol) | Inhibition of PTP1B activity (IC50~0.84 μM) Activation of insulin signaling and potentiate insulin sensitivity |
[172] |
| 3-Bromo-4,5-bis(2,3-dibromo-4,5-dihydroxybenzyl)-1,2-benzenediol isolated from the red alga Rhodomela confervoides | In vitro: palmitate-induced insulin resistance in C2C12 cells treated with bromophenol (0.5–2.0 μM for phenol) | Inhibition of PTP1B activity (IC50~2 μM) Activation of insulin signaling and prevent palmitate-induced insulin resistance |
[173] |
| Phlorofucofuroeckol-A, eckol, phloroglucinol, fucofuroeckol A, dieckol and 8,8′-bieckol isolated and crude phlorotannins from Lessoniaceae | In vitro assay: human and bovine serum albumin models | Inhibition of AGEs formation, crude phlorotannins showed IC50~0.43–0.53 mg/mL, and among the purified phlorotannins, phlorofucofuroeckol A was the most active (IC50~4.1–4.8 μM) | [177] |
| Methanolic extract from P. pavonica and Turbinaria ornate rich in phlorotannins | In vitro assay: BSA-glucose assay In vivo: Caenorhabditis elegans with induced hyperglycemia |
Inhibition of AGEs formation (IC50~15.16 μg/mL, 35.25 μg/mL and 22.70 μg/mL, respectively) Inhibition of AGEs formation |
[178] |
| Phlorofucofuroeckol-A isolated from E. stolonifera | In vitro assay for non-enzymatic insulin glycation | Inhibition of AGEs formation (IC50 29.50–43.55 μM for D-ribose and D-glucose-induced insulin glycation, respectively) | [179] |
| Octaphlorethol A isolated from Ishige foliacea | In vitro: STZ-induced pancreatic β-cell damage (RINm5F pancreatic β-cells) (12.5–50.0 μg/mL for phenol) | Decreased the death of STZ-treated pancreatic β-cells Decreased the TBARS and ROS Increased the activity of antioxidant enzymes |
[181] |
| 6,6-Bieckol, phloroeckol, dieckol and phlorofucofuroeckol isolated from E. cava | In vivo: high glucose-stimulated oxidative stress in Zebrafish, a vertebrate model (10–20 μM of phenols) | Inhibition of high glucose-induced ROS and cell death Dieckol reduced the heart rates, ROS, NO and lipid peroxidation Dieckol reduced the overexpression of iNOS and COX-2 |
[182] |
| Extract isolated from the red seaweed Polysiphonia japonica | In vitro: palmitate-induced damage in β-cells (Ins-1 cells) (1–10 μg/mL of extract) | Inhibited the palmitate-induced damage in β-cells Preserved the glucose-induced insulin secretion in β-cells |
[183] |
| Octaphlorethol A from Ishige foliacea | In vitro: rat myoblast L6 cells (6.25–50 μM of phenol) | Increased the glucose uptake Increased the Glut4 translocation to the plasma membrane, via Akt and AMPK activation |
[185] |
| Dieckol isolated from E. cava | In vivo: STZ-induced diabetic mice (acute, 100 mg/kg bw of dieckol administered orally) | Delayed the absorption of dietary carbohydrates | [187] |
| 2,7’’-Phloroglucinol-6,6’-bieckol from E. cava | In vivo: STZ-induced diabetic mice (acute, 10 mg/kg bw of phenol administered orally) | Delayed the absorption of dietary carbohydrates Inhibition of α-glucosidase and α-amylase activities (IC50 23.35 μM and 6.94 μM, respectively) |
[188] |
| Polyphenol-rich seaweed extract from F. vesiculosus | In vivo: 38 healthy adults (acute, 500 mg and 2000 mg of phenol) | No change in postprandial blood glucose and insulin levels | [189] |
| Dieckol isolated from brown seaweed E. cava | In vivo: a T2DM mouse model (C57BL/KsJ-db/db) (10 and 20 mg/kg bw of phenol for 14 days administered intraperitoneal injection) | Diminished the fasting blood glucose and insulin levels Diminished the body weight Decreased the TBARS Increased the activity of antioxidant enzymes in liver tissues Increased the levels of AMPK and Akt phosphorylation in muscle tissues |
[190] |
| Polyphenol-rich extracts from brown macroalgae L. trabeculata | In vitro assay: α-glucosidase and lipase inhibitory activities --- In vivo: high-fat diet and STZ-induced diabetic rats (200 mg/kg/day bw of phenol for 4 weeks by gavage) |
Inhibition of α-glucosidase and lipase activities (IC50 < 0.25 mg/mL) --- Diminished the fasting blood glucose and insulin levels Improved the serum lipid profile Improved the antioxidant stress parameters |
[103] |
| Water-ethanolic extract of green macroalgae Enteromorpha prolifera rich in flavonoids | In vivo: STZ-induced diabetic rats (150 mg/kg/day bw of phenol for 4 weeks by gavage) | Diminished the fasting blood glucose and improved oral glucose tolerance Hypoglycemic effect by increasing IRS1/PI3K/Akt and suppressing JNK1/2 in liver |
[191] |
| Dieckol-rich extract of brown algae E. cava | In vivo: 8 pre-diabetic adults (1500 mg per day for 12 weeks) | Decreased the postprandial glucose, insulin, and C-peptide levels | [192] |
GAE: gallic acid equivalents; PTP1B: protein tyrosine phosphatase 1B; AGEs: advanced glycation end-products; ROS: reactive oxygen species; TBARs: thiobarbituric acid reactive substances; NO: nitric oxide; iNOS: inducible nitric oxide synthase; COX-2: cyclooxygenase-2; Glut4: glucose transporter 4; Akt: protein kinase B; AMPK: AMP-activated protein kinase; PI3K: phosphoinositide 3-kinase; IRS1: Insulin receptor substrate 1; JNKs: c-Jun N-terminal kinases.