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 V_max, an increase of K_m, and K_ik/K_iv ratio ranging between 2.66 and 3.69.

Keywords:

• PTP1B
• α-glucosidase
• Paulowinia tomentosa
• enzyme inhibition
• kinetic analysis

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was done with research funds from the Ministry of Agriculture, Food and Rural Affairs through (IPET) (No. 315032-04-3-SB010) and Ministry of Education, through (NRF) (2015R1A6A1A03031413), of South Korea, and National Research Foundation of Korea. BK21 plus program supported scholarship for all students.