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

摘要

Abstract Context: Despite phytochemical studies of Agrimonia pilosa Ledeb. (Rosaceae), the antidiabetic effects of this plant are unknown. Objective: This study characterizes the isolated compounds from the aerial parts of A. pilosa and evaluates their PTP1B and α-glucosidase inhibitory properties. Materials and methods: Ethanol extract of A. pilosa was found to inhibit 64% PTP1B activity at 30?μg/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 α-glucosidase enzyme. Results: Compounds 1 – 11 were identified as apigenin-7-O-β- d -glucuronide-6″-methyl ester, triliroside, quercetin-7-O-β- d -glycoside, quercetin-3-O-β- d -glycoside, kaempferol, kaempferol-3-O-α- l -rhamnoside, β-sitosterol, ursolic acid, tormentic acid, methyl 2-hydroxyl tricosanoate, and palmitic acid. Compounds 8 , 9 , and 11 displayed inhibitory effects on PTP1B activity with IC₅₀ values of 3.47?±?0.02, 0.50?±?0.06, and 0.10?±?0.03?μM, respectively. Compounds 3 , 4 , 6 , and 9 exhibited inhibition of the α-glucosidase activity with IC₅₀ values of 11.2?±?0.2, 29.6?±?0.9, 28.5?±?0.1, and 23.8?±?0.4?μM, 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 α-glucosidase enzyme. This result suggested the potential of these compounds for developing antidiabetic agents.