Serrulatane diterpenoids from the leaves of Eremophila glabra and their potential as antihyperglycemic drug leads. (April 2022)

• Record Type: Journal Article
• Authors: Petersen, Malene J.; Liang, Chao; Kjaerulff, Louise; Ndi, Chi; Semple, Susan; Buirchell, Bevan; Coriani, Sonia; Møller, Birger Lindberg; Staerk, Dan
• Is Part Of: Phytochemistry. Volume 196(2022)
• Publication Date: 2022-04
• Subjects: Eremophila glabra -- Scrophulariaceae -- High-resolution inhibition profiling -- Serrulatane diterpenoids -- Flavonoids -- Protein-tyrosine phosphatase 1B -- α-Glucosidase; Bis-Tris bis(2-hydroxyethyl)amino-tris(hydroxymethyl)methane -- COSY correlation spectroscopy -- DMSO dimethyl sulfoxide -- DTT dithiothreitol -- ECD electronic circular dichroism -- EDTA N, N, N′, N′-ethylenediaminetetraacetate -- HMBC heteronuclear multiple-bond correlation -- HPLC high-performance liquid chromatography -- HRMS high-resolution mass spectrometry -- HSQC heteronuclear single quantum coherence -- NMR nuclear magnetic resonance -- NOE nuclear Overhauser effect -- PDA photodiode array -- p-NPG p-nitrophenyl α-D-glucopyranoside -- p-NPP p-nitrophenyl phosphate -- PTP1B protein-tyrosine phosphatase 1B -- ROESY rotating frame Overhauser effect spectroscopy -- T2D type 2 diabetes -- Tris tris(hydroxymethyl)-aminomethane; Botanical chemistry -- Periodicals; Biochemistry -- Periodicals; Botany -- Periodicals; Chimie végétale -- Périodiques; 572.2
• DOI: 10.1016/j.phytochem.2021.113072
• Languages: English
• ISSNs: 0031-9422

Abstract

Abstract: Eremophila (Scrophulariaceae) is a genus of Australian desert plants, which have been used by Australian Aboriginal people for various medicinal purposes. Crude extracts of the leaf resin of Eremophila glabra (R.Br.) Ostenf. showed α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with IC50 values of 19.3 ± 1.2 μg/mL and 11.8 ± 2.1 μg/mL, respectively. Dual α-glucosidase/PTP1B high-resolution inhibition profiling combined with HPLC-PDA-HRMS and NMR were used to isolate and identify the compounds providing these activities. This resulted in isolation of seven undescribed serrulatane diterpenoids, eremoglabrane A-G, together with nine previously identified serrulatane diterpenoids and flavonoids. Three of the serrulatane diterpenoids showed PTP1B inhibitory activities with IC50 values from 63.8 ± 5.8 μM to 104.5 ± 25.9 μM. Graphical abstract: Image 1 Highlights: Acetonitrile extract of Eremophila glabra resin inhibit PTP1B and α-glucosidase. Dual high-resolution inhibition profiling was used to pinpoint bioactive compounds. Seven undescribed serrulatane diterpenoids were isolated and structure elucidated. Three serrulatane diterpenoids exhibited PTP1B inhibition. One serrulatane diterpenoid exhibited α-glucosidase inhibition.