Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal medicines and constituents of Cinnamomum burmannii and Zingiber aromaticum

We screened water and methanol extracts of 28 Indonesian medicinal plants for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activities. Nine water extracts, i.e., Alstonia scholaris leaf, Blumea balsamifera, Cinnamomum burmannii, Cymbopogon nardus, Melaleuca leucadendra, Phyllanthus niruri, Piper nigrum, Syzygium aromaticum, and Sy. polyanthum, exhibited a parts per thousand yen70 % inhibition at 25 mu g/mL, whereas 11 methanol extracts, i.e., Als. scholaris, Andrographis paniculata, B. balsamifera, Ci. burmannii, Curcuma heyneana, Glycyrrhiza glabra, M. leucadendra, Punica granatum, Rheum palmatum, Sy. polyanthum, and Z. aromaticum, exhibited a parts per thousand yen70 % inhibition at 25 mu g/mL. Water extracts of B. balsamifera (IC50, 2.26 mu g/mL) and M. leucadendra (IC50, 2.05 mu g/mL), and methanol extracts of Ci. burmannii (IC50, 2.47 mu g/mL), Pu. granatum (IC50, 2.40 mu g/mL), and Sy. polyanthum (IC50, 1.03 mu g/mL) exhibited strong inhibitory activity, which was comparable with that of the positive control, RK-682 (IC50, 2.05 mu g/mL). The PTP1B inhibitory activity of the constituents of Ci. burmannii and Z. aromaticum was then evaluated. 5'-Hydroxy-5-hydroxymethyl-4aEuro(3),5aEuro(3)-methylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene (2; IC50, 29.7 mu M) and trans-cinnamaldehyde (5; IC50, 57.6 mu M) were the active constituents of Ci. burmannii, while humulatrien-5-ol-8-one (21; IC50, 27.7 mu M), kaempferol-3,4'-di-O-methyl ether (32; IC50, 17.5 mu M), and (S)-6-gingerol (33; IC50, 28.1 mu M) were those of Z. aromaticum. These results suggest that these medicinal plants may contribute to the treatment and/or prevention of type II diabetes and/or obesity through PTP1B inhibition.