Search

Eremophila bignoniiflora is a shrub distributed throughout inland northern and eastern Australia, and it has been used in several medicinal applications by some Australian Aboriginal people. In our continued search for anti-diabetic constituents from natural resources, the crude ethyl acetate extract of E. bignoniiflora was found to have protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC 50 value of 23.9 ± 1.9 μg/mL. High-resolution PTP1B inhibition profiling combined with HRMS and NMR were subsequently used to investigate the individual compounds responsible for the observed bioactivity of the crude extract. This led to identification of five undescribed 2(5H)-furanone sesquiterpenes, together with 13 flavonoids and phenolic compounds. Dose-response curves of the isolated compounds revealed that two 2(5H)-furanone sesquiterpene cinnamates and three flavonoids exhibited moderate PTP1B inhibitory activity with IC 50 values from 41.4 ± 1.4 to 154.5 ± 8.9 μM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Type 2 diabetes (T2D) constituted 90% of the global 387 million diabetes cases in 2014. The enzyme protein-tyrosine phosphatase 1B (PTP1B) has been recognized as a therapeutic target for treatment of T2D and its adverse complications. With the aim of accelerating the investigation of complex natural sources, such as crude plant extracts, for potential PTP1B inhibitors, we have developed a bio-analytical platform combining high-resolution PTP1B inhibition profiling and high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HR-bioassay/HPLC-HRMS-SPE-NMR. Human recombinant PTP1B enzyme was used for the microplate-based PTP1B inhibition assay, which was optimized for pH and substrate concentration to be compatible with rate measurements within the 10 min incubation time. Subsequently, analytical-scale HPLC-based microfractionation followed by colorimetric microplate-based PTP1B bioassaying enabled construction of a high-resolution inhibition profile corresponding to the HPLC profile. The high-resolution PTP1B inhibition profiling was validated using an artificial mixture of known PTP1B inhibitors and non-inhibiting compounds as negative controls. Finally, a proof-of-concept study with a real sample was performed using crude ethyl acetate extract of the phytochemically hitherto unexplored plant Eremophila lucida. This led to the identification of the first viscidane type diterpene, i.e., 5-hydroxyviscida-3,14-dien-20-oic acid (9) as PTP1B inhibitor with an IC50 value of 42.0 ± 5.9 μM. In addition, a series of flavonoids, i.e., luteolin (1), dinatin (3a), tricin (3b), 3,6-dimethoxyapigenin (4), jaceidin (5), and cirsimaritin (6) as well as a cembrene diterpene, (3Z, 7E, 11Z)-15-hydroxycembra-3,7,11-trien-19-oic acid (8), were also identified for the first time from E. lucida., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Short syntheses of cuniloside B and cypellocarpin C, (+)-(R)-oleuropeic acid-containing carbohydrates, are reported. Also disclosed are syntheses of the noreugenin glycosides, undulatoside A and corymbosins K(1) and K(2). Leaf extracts of 28 diverse eucalypts revealed cuniloside B to be present in all, and cypellocarpin C to be present in most, of the species examined. The widespread occurrence of these carbohydrate monoterpenoid esters supports their roles in essential oil biosynthesis or mobilization from sites of synthesis to secretory cavity lumena., (Copyright 2010 Elsevier Ltd. All rights reserved.)