Sterols from Centaurea pumilio L. with cell proliferative activity: In vitro and in silico studies
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Date
2023-04
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Series Info
De Gruyte;
Doi
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Abstract
Numerous studies highlighted the impact of
natural products, particularly phytosterols, in wound
healing while providing less expensive alternatives to che-
mically synthesized drugs, with less side effects. Centaurea
pumilio L. (family Asteraceae) is a rare and endangered
species of genus Centaurea with few reports concerning
its chemistry. Our phytochemical investigation for the
non-polar fraction of its aerial parts led to the isolation
and identification of the new compound (6) identified as
stigmast-1,5-dien-3-O-β-D-glucopyranoside along with five
known sterols and triterpenes (1–5) identified as taraxas-
terol, β-sitosterol, stigmasterol, β-sitosterol glucoside,
and stigmasterol-3-O-β-D-glucopyranoside. Structures of
the isolated compounds have been characterized using
1D, 2D NMR, and mass spectral analyses. The cell viability
and proliferative activity of the isolated compounds were
evaluated using an MTT assay on cultured human primary
umbilical vein endothelial cells (HUVEC). None of the com-
pounds exhibited any sign of cytotoxicity. Nonetheless, com-
pounds 5 and 6 moderately enhanced the HUVEC cell
growth by 14 and 16%, respectively, at the maximal tested
dose (50 µg/mL). As inhibition of glycogen synthase kinase
3-β (GSK3-β) enzyme is important to enhance the wound
healing process; therefore, molecular docking was per-
formed to understand the possible interactions between
bioactive compounds 5 and 6 and GSK-3β binding pocket
active amino acid residues. Both compounds were able to
bind to the substrate‑binding site of GSK-3β and poten-
tially interact with the key active site residues, forming
strong π and hydrogen interactions with the catalytic site
residues, revealing lower binding energy (−7.185 and
−6.303 kcal/mol, respectively) than that of indirubin-3-
monooxime (−5.303 kcal/mol); thereby representing strong
natural replacements candidates for GSK-3β inhibitors
Description
Keywords
Centaurea pumilio,, sterols,, triterpenes,, HUVEC,, growth stimulatory activity