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

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 32; no. 1; pp. 1195 - 1202
• Main Authors: Song, Yeong Hun, Uddin, Zia, Jin, Young Min, Li, Zuopeng, Curtis-Long, Marcus John, Kim, Kwang Dong, Cho, Jung Keun, Park, Ki Hun
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2017; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: alpha-Glucosidases - metabolism; Diabetes mellitus; Dose-Response Relationship, Drug; enzyme inhibition; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Flavonoids; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; Fruit - chemistry; Humans; Insulin; kinetic analysis; Leptin; Magnoliopsida - chemistry; Molecular Structure; Paulowinia tomentosa; Paulownia tomentosa; Phosphatase; Potassium; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Protein-tyrosine-phosphatase; PTP1B; Research Paper; Structure-Activity Relationship; α-Glucosidase; α-glucosidase; PTP1B; enzyme inhibition; kinetic analysis; Paulowinia tomentosa
• ISSN: 1475-6366; 1475-6374
• DOI: 10.1080/14756366.2017.1368502

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 (IC 50  = 1.9-8.2 μM) than α-glucosidase (IC 50  = 2.2-78.9 μM). Mimulone (1) was the most effective against PTP1B with IC 50  = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (8) displayed potent inhibition against α-glucosidase (IC 50  = 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.