Experimental and Computational Study to Reveal the Potential of Non-Polar Constituents from Hizikia fusiformis as Dual Protein Tyrosine Phosphatase 1B and α-Glucosidase Inhibitors

摘要

Hizikia fusiformis (Harvey) Okamura is an edible marine alga that has been widely used in Korea, China, and Japan as a rich source of dietary fiber and essential minerals. In our previous study, we observed that the methanol extract of H. fusiformis and its non-polar fractions showed potent protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibition. Therefore, the aim of the present study was to identify the active ingredient in the methanol extract of H. fusiformis. We isolated a new glycerol fatty acid (>13) and 20 known compounds including 9 fatty acids (>1–>3, >7–>12), mixture of 24R and 24S-saringosterol (>4), fucosterol (>5), mixture of 24R,28R and 24S,28R-epoxy-24-ethylcholesterol (>6), cedrusin (>14), 1-(4-hydroxy-3-methoxyphenyl)-2-[2-hydroxy -4-(3-hydroxypropyl)phenoxy]-1,3-propanediol (>15), benzyl alcohol alloside (>16), madhusic acid A (>17), glycyrrhizin (>18), glycyrrhizin-6’-methyl ester (>19), apo-9′-fucoxanthinone (>20) and tyramine (>21) from the non-polar fraction of H. fusiformis. New glycerol fatty acid >13 was identified as 2-(7′- (2″-hydroxy-3″-((5Z,8Z,11Z)-icosatrienoyloxy)propoxy)-7′-oxoheptanoyl)oxymethylpropenoic acid by spectroscopic analysis using NMR, IR, and HR-ESI-MS. We investigated the effect of the 21 isolated compounds and metabolites (>22 and >23) of >18 against the inhibition of PTP1B and α-glucosidase enzymes. All fatty acids showed potent PTP1B inhibition at low concentrations. In particular, new compound >13 and fucosterol epoxide (>6) showed noncompetitive inhibitory activity against PTP1B. Metabolites of glycyrrhizin, >22 and >23, exhibited competitive inhibition against PTP1B. These findings suggest that H. fusiformis, a widely consumed seafood, may be effective as a dietary supplement for the management of diabetes through the inhibition of PTP1B.