Macrocarpal C isolated from Eucalyptus globulus inhibits dipeptidyl peptidase 4 in an aggregated form

Abstract

Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A–C were isolated from Eucalyptus globulus through activity-guided fractionation and shown to be DPP-4 inhibitors. Of these, macrocarpal C showed the highest inhibitory activity, demonstrating an inhibition curve characterised by a pronounced increase in activity within a narrow concentration range. Evaluation of macrocarpal C solution by turbidity, nuclear magnetic resonance spectroscopy and mass spectrometry indicated its aggregation, which may explain the characteristics of the inhibition curve. These findings will be valuable for further study of potential small molecule DPP-4 inhibitors.

NMR Fingerprints of Formyl Phloroglucinol Meroterpenoids and Their Application to the Investigation of Eucalyptus gittinsii subsp. gittinsii

“…Likewise, acyclic diformyl phloroglucinols with NMR data reported in CD 3 OD also have C-6 carbons that are 7 ppm more deshielded compared to macrocarpal A ( 148 , Figure S11). Since NMR data for macrocarpals A–E ( 148 – 152 , Figure S11) ,, have been reported in both CD 3 OD and pyridine- d 5 , a comparison of this data suggests that C-1, C-2, C-4, and C-6 are slightly more deshielded (∼0.7 to 1.7 ppm) in pyridine- d 5 , while C-5 is approximately 2 ppm more deshielded in CD 3 OD. The chemical shifts of the two other phloroglucinol ring carbons are less than 0.5 ppm different in both NMR solvents, while C-1 and C-2 are approximately 2 ppm more deshielded and C-3 is 3 ppm more deshielded in pyridine- d 5 and CD 3 OD compared with CDCl 3 .…”

“…Likewise, acyclic diformyl phloroglucinols with NMR data reported in CD 3 OD also have C-6 carbons that are 7 ppm more deshielded compared to macrocarpal A (148, Figure S11). Since NMR data for macrocarpals A−E (148−152, Figure S11) 16,69,70 6).…”

Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans 

“…The inhibition of product formation is a way of controlling or modulating substrate ux through a metabolic pathway. If enzymes are sensitive to product inhibition, the output of the pathway will be suppressed [58][59][60][61][62].…”

Natural products from plants targeting key enzymes for the future development of antidiabetic agents

“…These compounds were generally less active than flavonoids, and no kinetic analysis has been performed. The active compounds are listed in Table 3, 100–109 and so far, boswelic acid derivative ( 151 ) showed the best activity level among terpenoids.…”