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

Authors

DOI:

https://doi.org/10.24959/nphj.26.211

Keywords:

lingonberry; fruit; inflammation; in silico; extract; carrageenan model.

Abstract

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.

References

  1. Nesci, S., Spagnoletta, A., & Oppedisano, F. (2023). Inflammation, mitochondria and natural compounds together in the circle of trust. International Journal of Molecular Sciences, 24(7), 6106. https://doi.org/10.3390/ijms24076106
  2. Al-Khayri, J. M., Sahana, G. R., Nagella, P., Joseph, B. V., Alessa, F. M., & Al-Mssallem, M. Q. (2022). Flavonoids as potential anti-inflammatory molecules: a review. Molecules, 27(9), 2901. https://doi.org/10.3390/molecules27092901
  3. Azab, A., Nassar, A., & Azab, A. (2016). Anti-Inflammatory Activity of Natural Products. Molecules, 21(10), 1321. https://doi.org/10.3390/molecules21101321
  4. Lu, Z., Wang, X., Lin, X., Mostafa, S., Zou, H., Wang, L., & Jin, B. (2024). Plant anthocyanins: classification, biosynthesis, regulation, bioactivity, and health benefits. Plant Physiology and Biochemistry, 217, 109268. https://doi.org/10.1016/j.plaphy.2024.109268
  5. Maslov, O. Y., Komisarenko, M. A., Kolisnyk, S. V., Antonenko, O. V., Kolisnyk, O. V., & Kostina, T. A. (2021). The study of the qualitative composition and the quantitative content of phenolic compounds in dietary supplements with lingonberry. Journal of Organic and Pharmaceutical Chemistry, 19(4/76), 40–46. https://doi.org/10.24959/ophcj.21.243782
  6. Ștefănescu, B.-E., Călinoiu, L. F., Ranga, F., Fetea, F., Mocan, A., Vodnar, D. C., & Crișan, G. (2020). Chemical composition and biological activities of the nord-west romanian wild bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea L.) leaves. Antioxidants, 9(6), 495. https://doi.org/10.3390/antiox9060495
  7. Kowalska, K. (2021). Lingonberry (Vaccinium vitis-idaea L.) fruit as a source of bioactive compounds with health-promoting effects–a review. International Journal of Molecular Sciences, 22(10), 5126. https://doi.org/10.3390/ijms22105126
  8. Thorakkattu, P., Jain, S., Sivapragasam, N., Maurya, A., Tiwari, S., Dwivedy, A. K., Koirala, P., & Nirmal, N. (2025). Edible berries-an update on nutritional composition and health benefits-part II. Current Nutrition Reports, 14(1), 10. https://doi.org/10.1007/s13668-024-00608-x
  9. Urbonaviciene, D., Bobinaite, R., Viskelis, P., Viskelis, J., Petruskevicius, A., Puzeryte, V., Cesoniene, L., Daubaras, R., Klavins, L., & Bobinas, C. (2023). Nutritional and physicochemical properties of wild lingonberry (Vaccinium vitis-idaea L.)–effects of geographic origin. Molecules, 28(12), 4589. https://doi.org/10.3390/molecules28124589
  10. Tsemenko, K. V., Kireiev, I. V., Komisarenko, M. A., & Koshovyi, O. M. (2018). Diuretychna aktyvnist fitosubstantsii iz lystia brusnytsi zvychainoi. Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky, 11(3/28), 312–317. https://doi.org/10.14739/2409-2932.2018.3.145276
  11. She, J., Hu, X., Deng, J., Fan, S., Zhang, Q., Nie, F., Zhang, J., Christian, M., Wang, Z., & Dai, X. (2024). Anthocyanin-rich lingonberry extract improves intestinal homeostasis based on intestinal stem cells in high-fat-diet-fed mice via gut microbiota-mediated Wnt/PPAR signaling. Food Bioscience, 62, 105411. https://doi.org/10.1016/j.fbio.2024.105411
  12. Huang, H., Luo, Y., Wang, Q., Zhang, Y., Li, Z., He, R., Chen, X., & Dong, Z. (2023). Vaccinium as potential therapy for diabetes and microvascular complications. Nutrients, 15(9), 2031. https://doi.org/10.3390/nu15092031
  13. Approximation of laws, regulations and administrative provisions of the member states regarding the protection of animals used for experimental and other scientific purposes. (2013, May 9). Council Directive № 86/609/EEC.
  14. Stefanov, O. V. (Red). (2001). Doklinichni doslidzhennia likarskykh zasobiv: metod. rek. Avitsena.
  15. Morris, G. M., Huey, R., & Olson, A. J. (2008). Using autodock for ligand‐receptor docking. Current Protocols in Bioinformatics, 24(1). https://doi.org/10.1002/0471250953.bi0814s24
  16. Burley, S. K., Bhatt, R., Bhikadiya, C., Bi, C., Biester, A., & Biswas, P. (2025). Updated resources for exploring experimentally-determined pdb structures and computed structure models at the RCSB protein data bank. Nucleic Acids Res, 53(D1), 564–574. https://doi.org/10.1093/nar/gkae1091
  17. Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., & He, S. (2025). PubChem 2025 update. Nucleic Acids Res, 53(D1), 1516–1525. https://doi.org/10.1093/nar/gky473
  18. Tian, W., Chen, C., Lei, X., Zhao, J., & Liang, J. (2018). CASTp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res, 46(W1), 363–367. https://doi.org/10.1093/nar/gkae1059
  19. Kondža, M., Brizić, I., & Jokić, S. (2024). Flavonoids as CYP3A4 inhibitors in vitro. Biomedicines, 12(3), 644. https://doi.org/10.3390/biomedicines12030644
  20. Vilkickyte, G., Raudone, L., & Petrikaite, V. (2020). Phenolic fractions from Vaccinium vitis-idaea L. and their antioxidant and anticancer activities assessment. Antioxidants, 9(12), 1261. https://doi.org/10.3390/antiox9121261
  21. Ibrahim, M. M., Elsaman, T., & Al-Nour, M. Y. (2018). Synthesis, anti-inflammatory activity, and in silico study of novel diclofenac and isatin conjugates. International Journal of Medicinal Chemistry, 2018, 1–11. https://doi.org/10.1155/2018/9139786

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Published

2026-03-31

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Vol. 111 No. 1 (2026): News of Pharmacy

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