RESUMO
Protein tyrosine phosphatase (PTP) 1B is a potential therapeutic target for type 2 diabetes. Phosphotyrosine (pTyr) mimetics still dominate the currently available PTP1B inhibitors. The phenoxyacetic acid moiety was taken as a pTyr mimetic herein and phenoxyacetic acid-based compounds 2a-2g and 3a-3c were designed. Among them, compounds 2a-2g exhibited potent inhibition against PTP1B, and compound 2g showed an IC50 of 0.42 μmol·L-1 against PTP1B. Compound 2f exhibited pharmacological profiles similar to that of rosiglitazone, and could improve the insulin sensitivity and the serum total cholesterol level. The results suggest that PTP1B inhibitors might be effective in treating type 2 diabetes as well as associated metabolic syndromes.
RESUMO
Objective: To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine. Methods: Water extracts of 18 plants were prepared through reflux and examined (25 mg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B (PTP1B). The determination of IC50 values was performed for the samples possessing more than 80% inhibition. Meanwhile, those exhibiting IC50 values more than 7.0 mg/mL were further profiled for their chemical constituents through nuclear magnetic resonance (NMR) measurement. Results: About 44% (8) of the examined samples showed more than 80% inhibition against PTP1B. The water extracts of Elephantopus scaber, Helicteres isora aerial parts, Elaeocarpus grandiflorus (E. grandiflorus) fruits, Melaleuca leucadendron leaves, and Quercus infectoria gum had IC50 values ranging from 2.05 to 6.90 mg/mL. Meanwhile, Andropogon nardus and Centella asiatica were at the area of d 3.0–4.0 ppm. Further, the 13C NMR observation of samples possessing the most intensive signals in their proton NMR Cinnamomum burmannii and E. grandiflorus showed the peaks at the area of d 60–90 ppm as the supportive evidence for sugar group signals. Intriguingly, a disaccharide from E. grandiflorus could be an active inhibitor towards PTB1B. Conclusions: In contrast to the mainstream solvents currently used in modern herbal manufactures especially Jamu medicine in Indonesia, pure-water-extracted materials should be reconsidered and could be reemerged for future studies and for the manufacture of herbal medicines. In addition, the activity of Jamu components should be confirmed that their antidiabetes and antiobesity activities could be through the inhibition of PTP1B.
RESUMO
Objective: To examine the potent of water as a solvent agent in the preparation of traditional herbal medicine. Methods: Water extracts of 18 plants were prepared through reflux and examined (25 μg/mL) to evaluate their possibility for inhibiting protein tyrosine phosphatase 1B (PTP1B). The determination of IC