The study of the anti-inflammatory activity of a thick lingonberry fruit extract in the carrageenan-induced rat paw edema model and molecular docking

Aim. To assess the anti-inflammatory activity of a concentrated lingonberry fruit extract using the carrageenan-induced rat paw edema model, complemented by the molecular docking analysis. Materials and methods. The study object was a concentrated lingonberry fruit extract. Molecular docking analyses were conducted using AutoDockTools 1.5.6, and the anti-inflammatory activity was evaluated using the carrageenan-induced paw edema model in rats. Results. The theoretical assessment of the anti-inflammatory activity of the lingonberry fruit extract showed that lingonberry anthocyanins, such as cyanidin-3-galactoside, cyanidin-3-arabinoside, blocked three of them highly selectively, such as cyclooxygenase (COX-2), phospholipase A2 and 5-lipoxygenase (5-LOX), and medium-selective nuclear factor kappa B (NF-kB). No highly selective inhibitor was found among anthocyanins of NF-kB. At the same time, сyanidin-3-glucoside blocked three out four targets, such as COX-2, phospholipase A2, 5-LOX. Although the widely used reference compounds in medicine and research – the synthetic drug diclofenac sodium and the natural flavonoid quercetin – demonstrated the inhibitory activity against pro-inflammatory enzymes, their binding affinities were moderate to low. The molecular docking analysis showed the following binding energy values (kcal/mol) for diclofenac sodium and quercetin: COX-2 (–5.76 and –4.59), phospholipase A2 (–7.65 and –6.79), 5-LOX (–6.00 and –6.45), and NF-κB (–3.00 and –3.61), respectively. Experimental studies have shown a thick lingonberry fruit extract in the dose of 13.0 mg/kg (calculated with reference to the total anthocyanins expressed as cyanidin-3-glycoside) reduces edema in 1, 2, 3 and 4 hours by 45 %, 35 %, 25 % and 24 %compared to the control group, respectively. Conclusions. A comprehensive theoretical and experimental study of the anti-inflammatory properties of the lingonberry fruit extract has been conducted using the molecular docking analysis and the carrageenan-induced rat paw edema model in vivo. The results in silico demonstrated that lingonberry anthocyanins exhibited a strong binding affinity toward key pro-inflammatory targets, including COX-2, phospholipase A2, 5-LOX, and NF-κB. The findings in vivo showed that administration of a thick lingonberry fruit extract in the dose of 13.0 mg/kg (calculated with reference to the total anthocyanins expressed as cyanidin-3-glycoside) significantly inhibited inflammatory responses in all phases of the carrageenan-induced paw edema.