Virtual screening-molecular docking-activity evaluation of Ailanthus altissima (Mill.) swingle bark in the treatment of ulcerative colitis

Abstract

Background: The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening-Molecular Docking-Activity Evaluation technology.

Methods: By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski's rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound's properties was achieved through in vitro experiments.

Results: Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were - 8.7, - 8.0, - 9.2, - 7.7, and - 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide.

Conclusion: Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential.

Keywords: Ailanthus altissima (Mill.) Swingle Bark; Evaluation; Molecular Docking; Ulcerative Colitis; Virtual screening.

Fig. 1

Binding pattern of the highest scoring compounds to human EGFR, IL-1R, TGFR, TLR, and Wnt8 proteins. The colored curly structure represents the amino acid spatial sequence of the target protein, and the yellow structure in the protein cavity represents small molecules. The free energies of binding to the active cavities of human EGFR, IL-1R, TGFR, TLR1 and Wnt proteins of the highest scoring compounds dehydrocrebanine (006315), ailanthone (006284), kaempferol (000422), ailanthone (006284), and ailanthone (006284) are − 8.7, − 8.0, − 9.2, − 7.7, and − 8.5 kcal/mol, respectively

Fig. 2

Microscopic binding of the highest scoring compound to amino acid residues near the active site of the target protein. Green circles and lines represent conventional hydrogen bonds; light blue circles and lines represent carbon hydrocarbon bonds; orange circles and lines represent π–cation interactions; pink circles and lines represent alkyls; and light pink circles and lines represent π–alkyl interactions. The letter and the number under the amino acid represent the abbreviated name and the primary structure of theamino acid sequence

Fig. 3

Inhibitory effect of ailanthone on cell proliferation. (A) The relative inhibition rate of ailanthone was tested on NCM460 cells by CCK-8 experiment. (B) The relative inhibition of ailanthone was tested on RAW264.7 cells by CCK-8 experiment. N = 6

Fig. 4

Ailanthone can inhibit the activity of TNF-α, IL-6, and IL-1β. The activity of the pro-inflammatory cytokines was observed in an ELISA experiment on RAW264.7 cells. N = 6. **P < 0.01