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(BAA),which is a traditional Chinese medicine,is widely used in Chinese folklore for the treatment of ulcerative colitis.Consequently, the objective of this study was to explore the therapeutic basis of BAA for the treatment of ulcerative colitis (UC) based on Virtual Screening–Molecular Docking–Activity Evaluation technology. Methods:By searching the Traditional Chinese Medicine (TCM) Systems Pharmacology (TCMSP) Database and Analysis Platform, 89 compounds from the chemical components of BAA were obtained. 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 UC-related target proteins and their binding modes by scoring function to identify the best candidate compounds.Additionally,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 UC-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energy of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins was −8.7, −8.0, −9.2, −7.7, and −8.5 kcal/mol, respectively. Potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained by 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, while ailanthone (10 μM) reduced the level of proinflammatory factors caused by lipopolysaccharide (LPS). Conclusion:Among the active components of BAA, ailanthone plays a major role in its anti-inflammatory properties . The present study shows that ailanthone has advantages in cell proliferation and inhibition of inflammation, but further animal research is needed to confirm the pharmaceutical potential thereof in the future.