**a.Brown seaweeds**

The brown seaweeds *Padina sulcata*, *Sargassum binderi*, and *Turbinaria conoides* have been reported to exhibit a potent inhibitory effect on the DPP-4 enzyme in a dose-dependent manner. The maximum inhibitory effect of *Padina sulcata*, *Sargassum binderi*, and *Turbinaria conoides* were observed as 83.09%, 81.75%, and 76.20%, at a concentration of 10 mg/ml, respectively. Further, crude water extracts of the above three brown seaweeds could secrete glucagon-like peptide-1 (GLP-1) to a greater extent than prevent hyperglycaemic conditions [42]. Similarly, ethyl acetate: methanol fraction (IC50: 0.013 mg/ml) of *Sargassum wightii* has been reported to exhibit an inhibitory effect on DPP-4 enzymes compared to the standard drug diprotein-A (IC50: 0.007 mg/ml) [43]. The methanol extract of *Turbinaria ornate* exhibited a strong inhibitory effect on the DPP-4 enzyme by 55.4% at 80 *μ*g/ml than the standard drug diprotin A (65%) might attribute to the presence of fucoids and sulfated polysaccharides in *T. ornata* [44].

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

The previous study conducted by Chin *et al.* [42] reported the inhibitory activity of green seaweed *Halimeda macroloba* on the DPP-4 enzyme. *Halimeda macroloba* inhibited the DPP-4 enzyme by 60.53% at a 10 mg/ml concentration compared to the positive control Berberine (75.92% at 1 mg/mL). Moreover, crude water extract of *H. macroloba* was able to stimulate glucagon-like peptide-1 (GLP-1) secretion.

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

The sulfated polygalactans isolated from red seaweeds *Kappaphycus alvarezii* and *Gracilaria opuntia* have been reported to possess the inhibitory effect on the DPP-4 enzyme. According to the results, sulfated galactans isolated from *Gracilaria opuntia* (IC50 0.09 mg/mL) significantly inhibited the DPP-4 enzyme than the sulfated galactans of *Kappaphycus alvarezii* (IC50 0.12 mg/mL) compared to the standard diprotin A (IC50 1.54 mg/mL). The observed activity might be due to the reaction between functional groups of sulfated polygalactan with DPP-4 by H-bonding and hydrophilic interactions [45]. Similarly, aqueous, alkaline, and a mixture of aqueous/alkaline fractions of a red seaweeds *Palmaria palmate* have exhibited a potent

inhibitory effect on DPP-4 enzyme with IC50 of 2.52 ± 0.05 mg/ml, 4.60 ± 0.09 mg/ ml, and 4.24 ± 0.02 mg/ml respectively [46]. Further studies reported that the red seaweed *Palmaria palmate's protein hydrolysate* had a potential inhibitory effect on the DPP-4 enzyme [40]. These results confirmed the possible inhibitory effect on DPP-4 enzymes of red seaweed extracts.
