**4.4 Inhibitory activity of protein tyrosine phosphatase 1B (PTP 1B)**

#### **a.Brown seaweed**

The brown seaweeds belonged to the genus "Sargassum" as reported to exhibit the potent inhibitory activity of PTP 1B enzyme due to the presence of secondary bioactive compounds. Ali *et al*. [51] reported that the hexane fraction (IC50: 1.83 *μ*g/ml) of *Sargassum serratifolium* strongly inhibited the PTP 1B enzyme than the standard ursolic acid (IC50: 1.12 *μ*g/ml). During the compound isolation, three plastoquinones (sargachromenol, sargahydroquinoic acid, and sargaquinoic acid) were identified, and among them, sargahydroquinoic acid exhibited a potent PTP 1B *Advanced Pharmacological Uses of Marine Algae as an Anti-Diabetic Therapy DOI: http://dx.doi.org/10.5772/intechopen.96807*

inhibitory effect (IC50:5.14 *μ*g/ml). Similarly, the chloroform extract of *Sargassum yezoense* (54.4%), *Sargassum fluvellum* (36.1%), *Sargassum horneri* (46.2%), Sargassum *sagmianum (21.4%),* Sargassum *hemiphyllum* (44.1%), and *Sargassum siliquastrum* (14.8%) could inhibit PTP 1B enzymes at 15 μg/ml of concentration [52]. Further, the phlorotannins such as eckol, 7-phloroeckol, and phlorofucofuroeckol-A isolated from *Ecklonia stolonifera, Ecklonia cava*, and *Eisenia bicyclis* could act as noncompetitive inhibitors on PTP 1B enzyme [53]. Moon *et al*. [32] further confirmed the inhibitory effect of phlorofucofuroeckol-A (IC50: 0.56 *μ*M), 7-phloroeckol (IC50: 2.09 *μ*M), and eckol (IC50: 2.64 *μ*M) isolated from *Ecklonia stolonifera* and *Eisenia bicyclis. Moreover, fucosterol isolated from Eisenia* bicyclis and *Ecklonia* stolonifera also showed PTP 1B inhibitory effect [54].

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

Several studies have been reported to elucidate the anti-diabetic potential of green seaweeds by enhancing insulin sensitivity through the mechanism of PTP 1B inhibition. Among the marine green seaweeds, Crude chloroform and methanol extract of a green seaweed *Derbesia marina* has been reported to exhibit an inhibitory effect on PTP 1B enzyme by 61.7% and 80.65 respectively at a concentration of 15 μg/ml. Further, the crude chloroform and methanol extract of edible green sea lettuce "*Ulva pertusa"* has exhibited potent PTP 1B inhibition at 15 μg/ml by 25.8% and 48.1%, respectively. Similarly, the crude chloroform and methanol extract of *Enteromorpha linza* (42.1%:35.4%) and *Codium adhaerens* (51.5%:71.2%) increased insulin sensitivity by inhibiting PTP 1B enzyme at 15 μg/ml concentration [52]. *Further, the compounds isolated from the green seaweeds belonged to the genus "Caulerpa" had a potent anti-diabetic effect by the mechanism of PTP 1B inhibition.* Racemosin C, Caulerpin, Caulerpic acid isolated from *Caulerpa racemosa,* and Caulersin isolated from *Caulerpa serrulata* have reported significant PTP1B inhibitor [55].

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

Most of the red seaweeds belonged to the genus "Chondus" exhibited antidiabetic activity via PTP 1B enzyme inhibition. According to the recorded studies, chloroform extract of *chondus ocellanthus* and *chondus crispus* inhibited PTP 1B enzymes by 41.5% and 27.6% at a concentration of 15 μg/ml. Similarly, red seaweeds belonged to the genus "Laurencia" had a potential inhibitory effect on PTP 1B enzyme. The methanol extract of *Laurencia okamurae* (33.1%) and chloroform extract of *Laurencia intermedia* (43.3%) could inhibit PTP 1B enzyme at 15 μg/ml of concentration. In addition to that 15 μg/ml concentration of chloroform extract of *Corallina pilulifera*, *Gymnogongrus flabelliformis*, and *Gracillaria textori* inhibited PTP 1B enzyme by 58.3%, 38.6%, and 24.9%, respectively [46]. Further, the compounds bromophenol and 3, 4-dibromo-5-(2-Bromo-3, 4-dihydroxy-6-(ethoxymethyl)benzyl)benzene-1,2-diol isolated from red seaweed, *Rhodomela confervoides* could increase insulin sensitivity via inhibition of PTP 1B enzyme [40].

#### **4.5 Inhibitory activity of angiotensin-converting enzymes (ACE)**

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

Phlorotannins eckol, phlorofucofuroeckol-A, and dieckol isolated from brown seaweed, *Ecklonia stolonifera* could inhibit angiotensin-converting enzyme with IC50 values of 70*:*82 *μ*M, 12*:*74 *μ*M, and 34*:*25 *μ*M, respectively. Among the isolated phlorotannins, dieckol acted as a non-competitive inhibitor of ACE [56]. Similarly, the

phloroglucinol isolated from the ethyl acetate fraction of Sargassum (56.96 μg/ml) wightii significantly inhibited the ACE compared to the positive control captopril (51.79 μg/ml) [57]. An amino acid sequence isolated from edible brown seaweed, *Undaria pinnatifida,* could significantly inhibit angiotensin-converting enzymes [57]. The protein-derived hydrolysate of *Undaria pinnatifida* exhibited a potent antihypertensive effect via inhibiting ACE [39]. Further, the enzymatic hydrolysate of *Ecklonia cava* has been reported to show a potent inhibitory effect on ACE with IC50 values from 2.33 up to 3.56 μg/mL [58].
