Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa

Abstract

Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1–8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1–5) and dihydroflavonols (6–8). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC50 = 1.9–8.2 μM) than α-glucosidase (IC50 = 2.2–78.9 μM). Mimulone (1) was the most effective against PTP1B with IC50 = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (8) displayed potent inhibition against α-glucosidase (IC50 = 2.2 μM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in Vmax, an increase of Km, and Kik/Kiv ratio ranging between 2.66 and 3.69.

Isolation and Characterization of Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Polyphenolic Compounds From Dodonaea viscosa and Their Kinetic Analysis

“…In order to validate the hypothesis that D. viscosa is a rich source of antidiabetic agents, all of the isolated polyphenolic compounds ( 1 - 9 ) were tested for their inhibitory potentials against PTP1B. Enzyme activity was determined using a previously established protocol with slight changes, in which hydrolysis of p -nitrophenyl phosphate was monitored spectrophotometrically (Song et al, 2017 ). As shown in Table 1 , all isolated constituents displayed significant inhibition against the target enzyme with IC 50 values ranging from 13.5 to 57.9 μM.…”

“…Protein tyrosine phosphatase 1B inhibitory assay was performed with slight modification to the previously reported method (Song et al, 2017 ). Tris–HCl buffer (25 mM, pH 7.5) which contained 1 mM (ethylenediaminetetraacetic acid) EDTA, 1 mM dithiothreitol (DTT), and 2 mM β-mercaptoethanol was used as buffer solution, whereas p -nitrophenyl phosphate ( p NPP), a substrate of PTP1B was utilized for enzyme activity measurement.…”

p‐Hydroxybenzyl alcohol inhibits four obesity‐related enzymes in vitro

“…Recent studies on antiobesity have targeted obesity‐related enzymes and have been studied as methods to inhibit their activity . The reason for choosing PL is that inhibition action of lipase, which plays an important role in lipid absorption, can prevent fat accumulation by allowing the lipid or fat to be excreted in the body without being digested or absorbed into the body .…”

Calebin-A, a Curcuminoid Analog Inhibits α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells

“…The direct effect of CBA on a purified yeast α-glucosidase preparation was assayed based on a method described previously [23] with some modifications. CBA was prepared in 0.05 M phosphate buffer at different concentrations and mixed with 100 µL of 1.2 mM p-nitrophenyl-α-D-glucopyranoside (pNG) substrate solution in a 96-well plate.…”