MECHANISM OF 15-LIPOXYGENASE INHIBITION BY DIOSMIN
DOI:
https://doi.org/10.11603/2312-0967.2023.2.14053Keywords:
diosmin, flavonoids, 15-lipoxygenase, inflammation, active pharmaceutical ingredient, molecular mechanismAbstract
The aim of the work. Study of the anti-inflammatory properties of diosmin using the method of evaluating the mechanism of inhibition of 15-lipoxygenase from soybeans (15-sLOX).
Materials and Methods. The study of inhibition of 15-sLOX by diosmin was performed by recording the formation of the conjugate at 234 nm using the spectrophotometric method. Linoleic acid was used as a substrate. The processing of experimental data included the calculation of steady-state velocities and kinetic parameters of inhibition and was carried out according to standard methods, the kinetics of the studied process were evaluated in the SigmaPlot 14.0 data analysis and visualization program.
Results and Discussion. It was established that diosmin inhibits 15-lipoxygenase with IC50=244.75±19.91 µM. When studying the mechanism of inhibition by diosmin 15-sLOX, it was found that the most suitable according to the criterion of the value of the correlation coefficient (R2=0.97106) is the Mixed (Partial) model, that is, a mixed (partial) type of inhibition. The kinetic constants for diosmin calculated according to the selected model have the following values: Ki=66.14±18.34 μM; Km=55.54±5.86 μM; Vmax=0.98±0.04 μM/sec.
Conclusions. It has been established that diosmin is a dose-dependent inhibitor of 15-lipoxygenase. The obtained results make it possible to consider the study of in vitro inhibition of 15-sLOX by diosmin and substances of a similar chemical structure as an effective way of studying the anti-inflammatory properties of substances at the stage of preclinical studies. The obtained data on the mechanism of inhibition can be used in the planning of pharmacological studies of flavonoids and in the initial stages of pharmaceutical development of new anti-inflammatory drugs.
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