**4.1 Inhibitory activity of carbohydrate hydrolyzing α-amylase and α-glucosidase enzymes**

#### **a.Brown seaweeds**

Among the brown seaweeds, "Ecklonia" and "Eisenia" genera have been reported to exert hypoglycemic effects through α-amylase and α-glucosidase inhibitory activities [30]. The observed hypoglycemic activity can be attributed to the presence of phlorotannins; eckol, dieckol, 6,6′-bieckol, phlorofucofuroeckol-A, and phloroglucinol, and 7-phloroeckol [31]. According to the reported studies, methanol extract of *Ecklonia cava* exercises its hypoglycemic effects through the inhibitory activity of α-glucosidase enzymes (IC50–10.7 *μ*M), compared to the standard acarbose used. Similar results were reported with phlorotannins isolated from *Ecklonia stolonifera* against the α-glucosidase enzyme. Dieckol (IC50:1.61 μM) and phlorofucofuroeckol-A (IC50:1.37 μM) isolated from *Ecklonia stolonifera* reported to exhibit the potent inhibitory activity of α-glucosidase enzymes compared to the standard drug (IC50: 51.65 μM). Similarly, eckol (IC50: 11.16 *μ*M) isolated from *Ecklonia maxima* demonstrated strong α-glucosidase inhibitory activity comparable to the isolated phloroglucinol (IC50: 1991 *μ*M). Besides, *Eisenia bicyclis* from genus

Eisenia reported possessing 87% of inhibitory effect on *α*-amylase at 1 mM concentration in addition to the inhibitory effect on α-glucosidase and advanced glycation end products. Moreover, isolated eckol (IC50: 22.78 *μ*M), dioxinodehydroeckol (IC50: 34.60 *μ*M) and phloroglucinol (IC50: 141.18 *μ*M) from *Eisenia bicyclis* exhibited potent *α*-glucosidase inhibitory activity [32].

A brown seaweed *Sargassum hystrix* reported to exhibit inhibitory effect on α-amylase IC50: 0*:*58 ± 0*:*01 mg/ml; IC50 acarbose: 0*:*53 ± 0*:*00 mg/ml) and α-glucosidase (IC50: 0*:*59 ± 0*:*02 mg/ml; IC50 acarbose: 0*:*61 ± 0*:*01 mg/ml) enzymes compared to the standard acarbose [33]. This was further confirmed by an *in-vivo* study using streptozotocin-induced rats and observed that the deduction of preprandial (186.4 mg/ml) and postprandial (186.9 mg/ml) blood glucose levels at 300 mg/kg concentration comparable to the standard drug glibenclamide (5 mg/ kg) (Pre-prandial;195.6 mg/ml; postprandial:104.8 mg/ml) without any adverse effects. Correspondingly, ethanol (150 mg/kg) and aqueous (300 mg/kg) extracts of *Sargassum polycystum* reported to reduce hyperglycaemic condition in diabetic rats [34]. Further studies has reported that a brown seaweed *Ascophyllum nodosum* effectively inhibited α-amylase (IC50: 0.1 *μ*g/ml) and α-glucosidase enzymes ((IC50: 19 *μ*g/ml) due to the presence of phlorotannins [35].

#### **b.Green seaweeds**

Green seaweeds belong to the genus "Ulva." They have been reported to possess hypoglycemic activity, and they have been used for various food dishes in Asians due to the presence of high soluble fiber content. The aqueous extract of green seaweeds *Ulva lactuca* (Inhibition-α-amylase: 83.4%; α-glucosidase: 61.81%) and *Ulva reticulate* (Inhibition-α-amylase: 89.1%; α-glucosidase: 76.02%) were effective against α-amylase and α-glucosidase enzymes at a concentration of 100 μg/ml after 8 hours of extraction period at 37 °C in a water bath as it gets more time to release the phytochemicals and colloids to the extract [36]. Similarly, the crude extract of *Ulva ohnoi* exhibited α-amylase inhibition by 41.7% and complete α-glucosidase inhibition at 10 mg/mL [37].

The methanol extract of a green seaweed *Chlorodesmis* inhibited α-amylase enzyme by 72% at 500 μg/ml with IC50 of 408.9 μg/ml without any effect on α-glucosidase enzymes. Similarly, chloroform extract of *Chaetomorpha aerea exhibited a potent inhibitory effect on α-amylase enzyme with* IC50 of 147.6 μg/ml. Besides, methanol extract of green seaweeds *Enteromorpha intestinalis (59%) and Cladophora rupestris (14%) exhibited a moderate and lower effect on the α-amylase inhibitory activity at a concentration of* 500 μg/ml [38]. Moreover, crude extracts of green seaweeds *Derbesia tenuissima and Oedogonium intermedium* were reported to exhibit lower α-amylase (53.6% and 49.2%) and potent α-glucosidase (73.98% and 69.5%) inhibitory effect at a concentration of 10 mg/ml [39]. Further studies reported that the green seaweed *Chlorella pyrenoidosa* could suppress the hyperglycaemic condition by inhibiting α-amylase and α-glucosidase enzymes. Besides, a green seaweed *Cladophora rupestris* has been reported to exhibit a hypoglycemic effect through α-amylase and α-glucosidase inhibitory mechanisms [40].

#### **c.Red seaweeds**

Among the marine red seaweeds, the genus "Gracillaria" was reported to possess the hypoglycemic effect through the inhibitory effect on α-amylase and α-glucosidase enzymes. Gunathilaka *et al*, [41] reported that the ethyl acetate fraction of red seaweed *Gracillaria edulis* exhibited potent α-amylase (IC50: 279.48 μg/ ml) and α-glucosidase (IC50: 87.92 μg/ml) inhibitory activity compared to the

*Advanced Pharmacological Uses of Marine Algae as an Anti-Diabetic Therapy DOI: http://dx.doi.org/10.5772/intechopen.96807*

standard acarbose (IC50amylase: 87.43 μg/ml; IC50glucosidase: 0.38 μg/ml) due to the presence of reported anti-diabetic compound 1H-Indole-2-carboxylic acid,6-(4-ethoxy phenyl)-3-methyl-4-oxo- 4,5,6,7-tetrahydro-isopropyl ester. Further studies reported that the aqueous extract of *Gracillaria edulis* inhibited the α-amylase and α-glucosidase enzyme by 87.86% and 79.55% at a concentration of 100 μg/ml. Similarly, *Gracilaria corticata* and *Acanthophora spicifera* had an inhibitory effect on α-amylase (84.66%; 54.73%) and α-glucosidase (73.53%; 46.86%) enzyme at a concentration of 100 μg/ml [36].
