| Int J Mol Sci. 2018 May 22;19(5). pii: E1542. |
| Protein Tyrosine Phosphatase 1B Inhibition and Glucose Uptake Potentials of Mulberrofuran G, Albanol B, and Kuwanon G from Root Bark of Morus alba L. in Insulin-Resistant HepG2 Cells: An In Vitro and In Silico Study.[Pubmed: 29786669] |
Type II diabetes mellitus (T2DM) is the most common form of diabetes and has become a major health problem across the world. The root bark of Morus alba L. is widely used in Traditional Chinese Medicine for treatment and management of diabetes.
METHODS AND RESULTS:
The aim of the present study was to evaluate the enzyme inhibitory potentials of three principle components, mulberrofuran G (1), albanol B (2), and Kuwanon G (3) in M. alba root bark against diabetes, establish their enzyme kinetics, carry out a molecular docking simulation, and demonstrate the glucose uptake activity in insulin-resistant HepG2 cells. Compounds 1⁻3 showed potent mixed-type enzyme inhibition against protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase. In particular, molecular docking simulations of 1⁻3 demonstrated negative binding energies in both enzymes. Moreover, 1⁻3 were non-toxic up to 5 μM concentration in HepG2 cells and enhanced glucose uptake significantly and decreased PTP1B expression in a dose-dependent manner in insulin-resistant HepG2 cells.
CONCLUSIONS:
Our overall results depict 1⁻3 from M. alba root bark as dual inhibitors of PTP1B and α-glucosidase enzymes, as well as insulin sensitizers. These active constituents in M. alba may potentially be utilized as an effective treatment for T2DM. |
| Eur J Med Chem. 2018 Jan 20;144:277-288. |
| Naturally occurring Diels-Alder-type adducts from Morus nigra as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B.[Pubmed: 29275228 ] |
Mycobacterium tuberculosis (Mtb) protein tyrosine phosphatases A and B (PtpA and PtpB) have been recognized as potential molecular targets for the development of new therapeutic strategies against tuberculosis (TB). In this context, we have recently reported that the naturally occurring Diels-Alder-type adduct Kuwanol E is an inhibitor of PtpB (Ki = 1.6 ± 0.1 μM).
METHODS AND RESULTS:
Here, we describe additional Diels-Alder-type adducts isolated from Morus nigra roots bark that inhibit PtpB at sub-micromolar concentrations. The two most potent compounds, namely Kuwanon G and Kuwanon H, showed Ki values of 0.39 ± 0.27 and 0.20 ± 0.01 μM, respectively, and interacted with the active site of the enzyme as suggested by kinetics and mass spectrometry studies. Molecular docking coupled with intrinsic fluorescence analysis and isothermal titration calorimetry (ITC) further characterized the interaction of these promising PtpB inhibitors. Notably, in an Mtb survival assay inside macrophages, Kuwanon G showed inhibition of Mtb growth by 61.3%.
CONCLUSIONS:
All these results point to the common Diels-Alder-type adduct scaffold, and highlight its relevance for the development of PtpB inhibitors as candidate therapeutics for TB. |
| J Ethnopharmacol. 2003 Feb;84(2-3):181-5. |
| Kuwanon G: an antibacterial agent from the root bark of Morus alba against oral pathogens.[Pubmed: 12648813] |
Kuwanon G was isolated from the ethyl acetate fraction of methanol extract of Morus alba and its structure was elucidated by 13C-NMR, 1H-NMR and FAB-MS.
METHODS AND RESULTS:
Antibacterial activity of Kuwanon G was investigated by the minimum inhibitory concentration (MIC) test and the viable cell count method. MIC of Kuwanon G against Streptococcus mutans causing dental caries was determined to be 8.0 microg/ml.
CONCLUSIONS:
The bactericidal test showed that Kuwanon G completely inactivated S. mutans at the concentration 20 microg/ml in 1 min. Kuwanon G also significantly inhibited the growth of other cariogenic bacteria such as Streptococcus sobrinus and Streptococcus sanguis, and Porpyromonas gingivalis causing periodontitis.
Transmission electron microscopy (TEM) of Kuwanon G treated cells demonstrated remarkable morphological damage of the cell wall and condensation of the cytoplasm. |
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