Neuroprotective Properties of Oleanolic Acid—Computational-Driven Molecular Research Combined with In Vitro and In Vivo Experiments
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Published:2023-08-31
Issue:9
Volume:16
Page:1234
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ISSN:1424-8247
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Container-title:Pharmaceuticals
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language:en
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Short-container-title:Pharmaceuticals
Author:
Stępnik Katarzyna12, Kukula-Koch Wirginia2ORCID, Plazinski Wojciech34ORCID, Rybicka Magda5ORCID, Gawel Kinga6ORCID
Affiliation:
1. Department of Physical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie–Sklodowska University in Lublin, Pl. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland 2. Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, ul. Chodzki 1, 20-093 Lublin, Poland 3. Department of Biopharmacy, Medical University of Lublin, ul. Chodzki 4a, 20-093 Lublin, Poland 4. Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, ul. Niezapominajek 8, 30-239 Kraków, Poland 5. Department of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, ul. Abrahama 58, 80-307 Gdańsk, Poland 6. Department of Experimental and Clinical Pharmacology, Medical University of Lublin, ul. Jaczewskiego Str. 8b, 20-090 Lublin, Poland
Abstract
Oleanolic acid (OA), as a ubiquitous compound in the plant kingdom, is studied for both its neuroprotective and neurotoxic properties. The mechanism of acetylcholinesterase (AChE) inhibitory potential of OA is investigated using molecular dynamic simulations (MD) and docking as well as biomimetic tests. Moreover, the in vitro SH-SY5Y human neuroblastoma cells and the in vivo zebrafish model were used. The inhibitory potential towards the AChE enzyme is examined using the TLC-bioautography assay (the IC50 value is 9.22 μM). The CH-π interactions between the central fragment of the ligand molecule and the aromatic cluster created by the His440, Phe288, Phe290, Phe330, Phe331, Tyr121, Tyr334, Trp84, and Trp279 side chains are observed. The results of the in vitro tests using the SH-SY5Y cells indicate that the viability rate is reduced to 71.5%, 61%, and 43% at the concentrations of 100 µg/mL, 300 µg/mL, and 1000 µg/mL, respectively, after 48 h of incubation, whereas cytotoxicity against the tested cell line with the IC50 value is 714.32 ± 32.40 µg/mL. The in vivo tests on the zebrafish prove that there is no difference between the control and experimental groups regarding the mortality rate and morphology (p > 0.05).
Funder
UNION OF LUBLIN UNIVERSITIES Medical University of Lublin
Subject
Drug Discovery,Pharmaceutical Science,Molecular Medicine
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