Dual high-resolution α-glucosidase/PTP1B bioassays coupled with HPLC-HRMS-SPE-NMR for investigation of 'Insulin plants' (Myrcia sp.) as new medicines for type 2 diabetes

Myrcia species or 'insulin plants' are used by indigenous communities in Brazil to treat type 2 diabetes [1]. Therapeutic targets for T2D include α-glucosidase- and protein tyrosine phosphatase 1B (PTP1B) inhibitors [2]. Herein, we report the screening of six Myrcia species for α-glucosidase and PTP1B inhibitory activity – M. guianensis (IC_50AG= 7.80 µg/mL; IC_50PTP1B= 3.26 µg/mL), M. rubella (IC_50AG= 4.36 µg/mL; IC_50PTP1B= 9.84 µg/mL), M. torta (IC_50AG= 5.80 µg/mL; IC_50PTP1B= 27.00 µg/mL), M. variabilis (IC_50AG= 3.17 µg/mL; IC_50PTP1B= 1.10 µg/mL), M. vestita (IC_50AG= 13.60 µg/mL; IC_50PTP1B= 2.83 µg/mL), and M. virgata (IC_50AG= 6.30 µg/mL; IC_50PTP1B= 3.00 µg/mL). M. rubella was chosen for further analyses, and the crude ethyl acetate extract was submitted to dual high-resolution α-glucosidase and PTP1B profiling for identification of bioactive constituents. Extensive analyses using HPLC-HRMS-SPE-NMR [3] led to the identification of 36 compounds including the α-glucosidase inhibitors – 4,5-dicaffeoylquinic acid (IC50AG = 1.98µM), isoquercitrin (IC50AG = 22.4µM), quercetin 3-O-β-D-glucuronide (IC₅₀AG = 21.30µM), and quercetin 3-O-(6''-malonylglucoside) (IC₅₀AG = 6.60µM). PTP1B inhibition was associated with triterpenes such as arjunolic acid and 3,4,3'-tri-O-methylellagic acid.

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[1] Cascaes MM, Guilhon GMSP, Andrade EHA, Zoghbi MGB, Santos LS. Int J Mol Sci 2015; 16: 23881 – 23904.

[2] Zhang S, Zhang Z-Y. Drug Discov Today 2007; 12: 373 – 381.

[3] Wubshet SG, Tahtah Y, Heskes AM, Kongstad KT, Pateraki I, Hamberger B, Møller BL, Staerk D. J Nat Prod 2016; 79: 1063 – 1072.