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

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.

[Ruyi Jinhuang Plaster suppresses BPH by reducing the expressions of P38, JNK2, NF-кBP65 and STAT3 in the prostate tissue of rats].

OBJECTIVE: To investigate the effect of Ruyi Jinhuang Plaster (RJP) on testosterone propionate-induced BPH in the rat model and its action mechanisms. METHODS: Forty-eight SD male rats were randomly divided into six groups of equal number: normal control, BPH model control, finasteride, and high-, medium- and low-dose RJP. The BPH model was made in the latter five groups by hypodermic injection of testosterone propionate. From the first day of modeling, the rats of the normal control and BPH model control groups were treated with blank plasters and those of the high-, medium- and low-dose RJP groups with RJPs at 42.0, 21.0 and 10.5 cm2/kg applied to the dehaired area of the back, and those of the finasteride group by gavage of finasteride at 4.5 mg/kg, all once a day for 30 successive days. Then the prostates of the animals were harvested for observation of histopathological changes by HE staining, measurement of the areas of interstitial and epithelial cells and prostatic glandular cavity, and determination of the expressions of P38, JNK2, NF-кBP65 and STAT3 proteins in the prostate tissue by Western blot. RESULTS: Compared with the BPH model controls, the high-dose RJP group showed significantly decreased proliferation and area proportion of prostatic epithelial cells (P < 0.05), increased area proportion of the prostatic glandular cavity (P < 0.05), and reduced expressions of P38, p-P38, NF-кBP65, P-NF-кBP65, STAT3, P-STAT3 and JNK2 in the prostate tissue (P < 0.05); the medium-dose RJP group exhibited markedly down-regulated expressions of JNK2 and NF-кBP65 (P < 0.05) but an up-regulated level of p-JNK (P < 0.05); while the low-dose RJP group displayed a remarkably reduced expression of JNK2 (P < 0.05) but an elevated level of p-JNK (P < 0.05). CONCLUSIONS: RJP suppresses BPH in the model rat by down-regulating the expressions of P38, p-P38, NF-кBP65, P-NF-кBP65, STAT3, P-STAT3 and JNK2 or up-regulating that of p-JNK in the prostate tissue.