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

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-ß-d-glucuronide-6″-methyl ester, triliroside, quercetin-7-O-ß-d-glycoside, quercetin-3-O-ß-d-glycoside, kaempferol, kaempferol-3-O-α-l-rhamnoside, ß-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.

Protein tyrosine phosphatase 1B (PTP1B) inhibitory constituents from the aerial parts of Tradescantia spathacea Sw.

Inhibitors of protein tyrosine phosphatase 1B (PTP1B) are promising agents for the treatment of type 2 diabetes and obesity. The bioactivity-guided isolation led to the separation of two new compounds, (±)-tradescantin (13) and tradescantoside (16), along with fourteen known compounds (1-12, 14, and 15) from the aerial parts of Tradescantia spathacea Sw. (Commelinaceae). Their chemical structures were elucidated by spectroscopic methods as well as by comparing with those reported in the literature. The isolated compounds (1-16) were then examined for their inhibitory activity toward PTP1B. The results indicated that compounds 2, 6, 8, and 12 possessed potent inhibition with IC50 values of 7.82±0.79, 6.80±0.89, 4.55±0.92, and 6.38±0.14 µM, respectively. Kinetic study of compounds 2, 6, 8, 12, 13, and 16 was conducted and the structure-activity relationships of the isolated compounds (1-16) were also discussed herein. To the best of our knowledge, all the isolates were separated for the first time from this plant.