Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitors from Morinda citrifolia (Noni) and Their Insulin Mimetic Activity

Abstract

As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.

Morinda citrifolia Linn. (Noni) and Its Potential in Obesity-Related Metabolic Dysfunction

“…The most important lignans isolated from noni fruit are americanin A, americanol A, episesamin 2,6-dicatechol, isoprincepin, lirioresinol, lirioresinol B dimethyl ether, morindolin, and 3,3’-bisdemethypinoresinol. These lignans improve parameters in obesity and associated disorders/diseases [58,59,61,76]. …”

“…Ursolic acid and related triterpene compounds, such as oleanolic acid, betulinic acid, uvaol, and α- and β-amyrin are widespread in many plants [77,78]. The most abundant triterpenoid from noni is ursolic acid, which has been widely investigated because of its hypoglycemic property [61,67,68]. …”

“…Intensive research efforts have evaluated the positive effects of Morinda citrifolia on glucose homeostasis in models of T2DM [49,61,73,76]. Nguyen et al [61] observed that methanolic Morinda citrifolia extract (part not identified) showed an anti-diabetic effect in vitro.…”

“…Nguyen et al [61] observed that methanolic Morinda citrifolia extract (part not identified) showed an anti-diabetic effect in vitro. The extract exhibited stimulatory effects on glucose uptake using a fluorescent-tagged glucose probe (2-NBDG) in 3T3-L1 adipocyte cells.…”

Protein tyrosine phosphatase 1B inhibitory activities of compounds isolated from Polygonum cuspidatum

“…Protein tyrosine phosphatase 1B (human recombinant) was purchased from Biomol International LP, Plymouth Meeting, PA, USA, and the inhibitory activities of the isolated anthraquinones were evaluated using p-nitrophenyl phosphate (p-NPP) as substrate. [3,4] Briefly, to each of 96 wells (final volume: 200 μL) was added 2 mM pNPP and PTP1B (0.05-0.1 μg) 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. Following incubation at 37 °C for 30 min, the reaction was terminated with 10 N NaOH.…”