Antihyperglycemic and anti-type 2 diabetic activity of marine hydroquinone isolated from brown algae (Dictyopteris polypodioides)

Abstract

Background and aims: Brown algae (Dictyopteris polypodioides) extract (DP) presented high inhibitory potential against α-amylase. The present study aims to isolate, purify and evaluate the antihyperglycemic and anti-type 2 diabetic activities of marine hydroquinone from DP.

Methods: Marine hydroquinones were isolated using silica gel, HPLC, and NMR spectroscopy was used to identify compound 1 and compound 2 as zonarol and isozonarol, respectively. The anti-hyperglycemic and anti-type 2 diabetic activities of zonarol were investigated by in vitro assay (α-amylase, α-glucosidase), Lineweaver-Burk plot and Type 2 diabetes mellitus model (T2DM) mice induced by streptozotocin (STZ).

Result: Zonarol had the highest content and the strongest inhibitory activity against α-glucosidase (IC₅₀ value of 6.03 mg L^-1) and α-amylase (IC₅₀ value of 19.29 mg L^-1) in a competitive inhibition and mix-type manner, respectively. The maltose and starch loading tests revealed that zonarol significantly reduced postprandial glycemia after 30 min loading (9.12 and 8.12 mg/dL, respectively), compared to normal (11.37 and 12.37 mg/dL, respectively). Zonarol exhibited pancreatic islet cell rejuvenation, as evidenced by increased pancreatic islet mass, and hence helps in the restoration of insulin levels and therefore improves the glucose metabolism in STZ-induced diabetic mice. Zonarol treatment in T2DM elevated abundant levels of main SCFAs (propionate, butyrate, and valeric acid), which are closely related to glucose metabolism homeostasis.

Conclusion: Our finding indicates that zonarol could be used as a food supplement to treat hyperglycemia and diabetes.

Keywords: Anti-hyperglycemia; Antidiabetic; Marine hydroquinone; brown algae; α-amylase; α-glucosidase.

Graphical abstract

Fig. 1

The inhibition kinetics of α-glucosidase (A) and α-amylase (B) by zonarol. Values are means ± SD, n = 3.

Fig. 2

The effect of zonarol on the blood glucose level after maltose (A) or starch (B) loading in mice. Values are means ± SEM, n = 6. ^#p < 0.05, compared with control group; ∗p < 0.05, compared with acarbose group.

Fig. 3

Effect of the 4-week treatment of zonarol on fasting blood glucose (A) and insulin levels (B) in streptozotocin-induced diabetic mice. NC, normal control group; T2DM, Type 2 Diabetes group; ZT 20, zonarol 20 mg/kg administered group; ZT 40, zonarol 40 mg/kg administered group; ZT 80, zonarol 80 mg/kg administered group. Values are means ± SEM, n = 6. Data with different letters are significantly different (p < 0.05).

Fig. 4

The improvement of zonarol on insulin resistance and glucose tolerance test in T2DM mice. (A) The insulin resistance index (HOMA-IR), (B) the insulin-sensitive index (ISI), and (C) the glucose tolerance test. NC, normal control group; T2DM, Type 2 Diabetes group; ZT 20, zonarol 20 mg/kg administered group; ZT 40, zonarol 40 mg/kg administered group; ZT 80, zonarol 80 mg/kg administered group. Values are means ± SEM, n = 6. Data with different letters are significantly different (p < 0.05).

Fig. 5

Hematoxylin and eosin-stained sections of pancreas stained after 4-week treatment of zonarol. Photomicrograph of a pancreatic islet used for morphometric analysis ( × 20). The major and minor ^a,b bright angle diameter and the surface area of the pancreas. NC, normal control group; T2DM, Type 2 Diabetes group; ZT 20, zonarol 20 mg/kg administered group; ZT 40, zonarol 40 mg/kg administered group; ZT 80, zonarol 80 mg/kg administered group.

Fig. 6

Effects of zonarol on the production of short-chain fatty acids (SCFAs) in feces of T2DM. NC, normal control group; T2DM, Type 2 Diabetes group; ZT 20, zonarol 20 mg/kg administered group; ZT 40, zonarol 40 mg/kg administered group; ZT 80, zonarol 80 mg/kg administered group. Values are means ± SEM, n = 6. Data with different letters are significantly different (p < 0.05).