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

Abstract

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.

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

“…In a patent application, GA was also shown to reduce the lipid synthesis or formation of very-low-density lipoproteins (VLDL’s) [ 37 ]. Moreover, both GA epimers (18α and 18β) have been identified as weak competitive PTP1B inhibitors [ 38 , 39 ]. Interestingly, GA can cross the blood-brain barrier [ 40 , 41 ] which is an essential property in the context of PTP1B inhibitors.…”

Hizikia fusiformis: Pharmacological and Nutritional Properties

“…Additionally, H. fusiformis contains fucosterol, a phytosterol with a non-polar component isolated from methanol extracts [ 71 ]. The total fucosterol concentrations in normal H. fusiformis extract (NH) and modified H. fusiformis extract (EH) were 0.249 and 1.067 mg/g, respectively [ 70 ].…”

“…Saringosterol is a non-polar sterol found in algae and is derived from methanol [ 6 , 71 ]. Studies have examined the chemical structures of H. fusiformis sterols, 24S-saringosterol and 24R-saringosterol [ 6 , 86 ].…”

Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome?

“…G. glabra contains more than 10 GLR-related saponins (Schmid, Dawid, Peters, & Hofmann, 2018). The product has been found also in other Glycyrrhiza species such as G. triphylla (Shakeri et al, 2018) and in an edible marine alga Hizikia fusiformis (Harvey) Okamura, a brown seaweed (Seong et al, 2019;Wagle et al, 2018). The name derives from the Greek word 'glykosrhiza' or sweet root.…”