Protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and glucosidase inhibitory activity of compounds isolated fromAgrimonia pilosa

Abstract

Objective: This study characterizes the isolated compounds from the aerial parts of A. pilosa and evaluates their PTP1B and a-glucosidase inhibitory properties. Materials and methods: Ethanol extract of A. pilosa was found to inhibit 64% PTP1B activity at 30 mg/mL. The ethanol extract was partitioned with methylene chloride, ethyl acetate, n-butanol, and water fractions. Among these, the ethyl acetate fraction displayed the most potent PTP1B activity. The ethyl acetate extract was separated by chromatographic methods to obtain flavonoids and triterpenoids (1-11); which were evaluated for their inhibitory effects on PTP1B activity with p-nitrophenyl phosphate (p-NPP) as a substrate, and also a-glucosidase enzyme. Results: Compounds 1-11 were identified as apigenin-ursolic acid, tormentic acid, methyl 2-hydroxyl tricosanoate, and palmitic acid. Compounds 8, 9, and 11 displayed inhibitory effects on PTP1B activity with IC 50 values of 3.47 ± 0.02, 0.50 ± 0.06, and 0.10 ± 0.03 mM, respectively. Compounds 3, 4, 6, and 9 exhibited inhibition of the a-glucosidase activity with IC 50 values of 11.2 ± 0.2, 29.6 ± 0.9, 28.5 ± 0.1, and 23.8 ± 0.4 mM, respectively. Discussion and conclusion: As major ingredients of A. pilosa, compounds 1, 6, 8, and 9 showed the greatest inhibitory potency on PTP1B activity. Compounds 3, 6, 8, and 9 also showed potent inhibitory effects on a-glucosidase enzyme. This result suggested the potential of these compounds for developing antidiabetic agents.

α-Glucosidase inhibition by flavonoids: anin vitroandin silicostructure–activity relationship study

“…Some flavonoids, such as morin 17 , luteolin 26 , baicalein 27 , kaempferol 28 and apigenin 24 , have been shown to exhibit inhibitory effects against α-glucosidase enzymes. Nevertheless, the information found in the literature is disperse and variable, probably due to the use of different enzyme concentrations (0.3–1.7 U/mL) 8 , 29 , 30 , from different origins (e.g.…”

“…Nevertheless, the information found in the literature is disperse and variable, probably due to the use of different enzyme concentrations (0.3–1.7 U/mL) 8 , 29 , 30 , from different origins (e.g. yeast and rat intestinal α-glucosidase) 18 , 19 , 31 , 32 , different substrates concentrations (1–20 mM) 19 , 30 , 33 and incubation time with the flavonoids (5 min–3 h) 8 , 26 , 28 , 29 , 34 . The discrepancies between the studies bring difficulties to their comparison and consequently the conclusions about the flavonoids efficacy against α-glucosidase activity.…”

Chemistry, Biological Activities and In Silico Bioprospection of Sterols and Triterpenes from Mexican Columnar Cactaceae

“…Deoxyviperidone, 5β-deoxyviperidone, and lathosterol had good scores against PTP1B and PPAR-γ, which could be a good combination of bio targets for the treatment of diabetes mellitus type 2. Well known antidiabetic sterols like fucosterol, lophenol and β-sitosterol have demonstrated in several studies their potential to regulate at different levels both PTP1B and/or PPAR proteins [61,216,217]. Although lophenol does not belong to the top 10 molecules with higher theoretical affinity, the Moldock score values for both PPAR-α and PPAR-γ proteins were -130.9 and -129.7, suggesting that the methodology used correctly predicts the biological activity.…”

A New Tannin from Fruits of Torreya Nucifera with Protein Tyrosine Phosphatase 1B Inhibitory Activity

“…The enzyme activity was measured using p-nitrophenyl phosphate (pNPP) as described previously [13]. Each 96 well (final volume: 100 l) was added 2 mM pNPP and PTP1B (0.05-0.1 g) in a buffer containing 50 mM citrate (pH 6.0), 0.1 M NaCl, 1 mM EDTA, and 1 mM dithiothreitol (DTT), with or without test compounds.…”