Phytochemical profile and angiotensin I converting enzyme (ACE) inhibitory activity of Limonium michelsonii Lincz

Members of the genus Limonium are widely used as medicinal herbs due to their health-promoting effects, such as an ability to improve blood circulation by inhibiting angiotensin I converting enzyme (ACE). While the potential of L. michelsonii Lincz. (a medicinal plant endemic to Kazakhstan) to inhibit ACE has been demonstrated, the inhibitory activities of its secondary metabolites have not been explored. In this work, the principal phenolic compounds (1–20) among these metabolites were isolated to determine the components responsible for ACE inhibition. The natural abundances of the active constituents within the target plant were characterized by UPLC-Q-TOF/MS analysis. All of the isolated compounds except for gallates 10–12 were found to significantly inhibit ACE, with IC₅₀ values of between 7.1 and 138.4 μM. Unexpectedly, the flavonol glycosides 16–20 were observed to be more potent than the corresponding aglycones 4 and 5. For example, quercetin (4) had IC₅₀ = 30.3 μM, whereas its glycosides (16, 17) had IC₅₀ = 10.2 and 14.5 μM, respectively. A similar trend was observed for myricetin (5) and its glycosides (18–20). In a kinetic study, the flavonols 3–5 and 16–20 and the dihydroflavonols 8 and 9 behaved as competitive inhibitors, whereas other flavones (1, 2, 13–15) and flavanones (6, 7) performed noncompetitive inhibition.