Significance of Astragaloside IV from the Roots of Astragalus mongholicus as an Acetylcholinesterase Inhibitor-From the Computational and Biomimetic Analyses to the In Vitro and In Vivo Studies of Safety

Katarzyna Stępnik; Wirginia Kukula-Koch; Wojciech Plazinski; Kinga Gawel; Katarzyna Gaweł-Bęben; Daariimaa Khurelbat; Anna Boguszewska-Czubara

doi:10.3390/ijms24119152

Significance of Astragaloside IV from the Roots of Astragalus mongholicus as an Acetylcholinesterase Inhibitor-From the Computational and Biomimetic Analyses to the In Vitro and In Vivo Studies of Safety

Int J Mol Sci. 2023 May 23;24(11):9152. doi: 10.3390/ijms24119152.

Authors

Katarzyna Stępnik¹, Wirginia Kukula-Koch², Wojciech Plazinski^{3

4}, Kinga Gawel⁵, Katarzyna Gaweł-Bęben⁶, Daariimaa Khurelbat⁷, Anna Boguszewska-Czubara⁸

Affiliations

¹ Department of Physical Chemistry, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Skłodowska University in Lublin, Pl. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland.
² Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, 1 Chodzki Str., 20-093 Lublin, Poland.
³ Department of Biopharmacy, Medical University of Lublin, Chodźki Str. 4a, 20-093 Lublin, Poland.
⁴ Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek Str. 8, 30-239 Kraków, Poland.
⁵ Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego Str. 8b, 20-090 Lublin, Poland.
⁶ Department of Cosmetology, University of Information Technology and Management in Rzeszów, Sucharskiego 2, 35-225 Rzeszów, Poland.
⁷ Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, Mongolian National University of Medical Sciences, Zorig Str., Ulaanbaatar 14210, Mongolia.
⁸ Department of Medical Chemistry, Medical University of Lublin, Chodźki 4A, 20-093 Lublin, Poland.

Abstract

The main aim of the study was to assess the acetylcholinesterase-inhibitory potential of triterpenoid saponins (astragalosides) found in the roots of Astragalus mongholicus. For this purpose, the TLC bioautography method was applied and then the IC₅₀ values were calculated for astragalosides II, III and IV (5.9 μM; 4.2 μM, and 4.0 μM, respectively). Moreover, molecular dynamics simulations were carried outto assess the affinity of the tested compounds for POPC and POPG-containing lipid bilayers, which in this case are the models of the blood-brain barrier (BBB). All determined free energy profiles confirmed that astragalosides exhibit great affinity for the lipid bilayer. A good correlation was obtained when comparing the logarithm of n-octanol/water partition coefficient (logPow) lipophilicity descriptor values with the smallest values of free energy of the determined 1D profiles. The affinity for the lipid bilayers changes in the same order as the corresponding logPow values, i.e.,: I > II > III~IV. All compounds exhibit a high and also relatively similar magnitude of binding energies, varying from ca. -55 to -51 kJ/mol. Apositive correlation between the experimentally-determined IC₅₀ values and the theoretically-predicted binding energies expressed by the correlation coefficient value equal 0.956 was observed.

Keywords: IC50; SH-SY5Y; acetylcholinesterase; free energy; lipophilicity; molecular docking; safety; zebrafish.

MeSH terms

Acetylcholinesterase / metabolism
Astragalus propinquus / chemistry
Biomimetics
Cholinesterase Inhibitors / metabolism
Cholinesterase Inhibitors / pharmacology
Lipid Bilayers / metabolism
Saponins* / chemistry
Triterpenes* / chemistry

Substances

astragaloside A
Acetylcholinesterase
Cholinesterase Inhibitors
Lipid Bilayers
Triterpenes
Saponins

Grants and funding

The paper was partially supported by BS/WCh/KChF-2023, Maria Curie-Skłodowska University in Lublin as well as by DS448, DS24, Medical University of Lublin.