In silico prediction of in vivo toxicity - the first steps of the e-Tox consortium

2010 ◽  
Vol 196 ◽  
pp. S250-S251
Author(s):  
T. Steger-Hartmann ◽  
F. Pognan ◽  
F. Sanz ◽  
C. Diaz ◽  
A. Sutter ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Yushi Ding ◽  
Suyun Yu ◽  
Zhonghong Wei ◽  
Rui Deng ◽  
Peng Chen ◽  
...  

Relieving Sore Throat Formula (RSTF) is a formula approved by the China Food and Drug Administration and has been used for the treatment of pharyngitis in clinic for many years. However, the potential pharmacological mechanism still remains unknown. We combined multiple methods including bioinformatics data digging, network pharmacology analysis, and pathway analysis to predict the potential target of RSTF. We verified our in silico prediction results with an in vivo/vitro antibacterial effect test, mouse phagocytic index test, proliferation, transformation, and migration of mouse spleen lymphocytes. Alteration of NF-κB pathway was determined by Western blotting, immunofluorescence, and PCR. The in vivo experiments demonstrated that the RSTF could significantly relieve the symptoms of pharyngitis. A rat saliva secretion test showed that RSTF can effectively relieve the xerostomia symptom. A phenol red excretion test showed that RSTF has an eliminating phlegm effect. A hot plate method and granuloma experiment proved that RSTF also have analgesic and anti-inflammatory effects. In silico prediction demonstrates that 70 active compounds of RSTF were filtered out through ADME screening and 84 putative targets correlated with different diseases. Pathway enrichment analysis showed that the candidate targets were mostly related to the response to bacteria and immunity signalling pathways, which are known contributors to pharyngitis. Experimental results confirmed that RSTF exerted therapeutic effects on pharyngitis mainly by antibacterial effect and downregulation of NF-κB activities. It is demonstrated both in silico and in vivo/vitro that RSTF exerted therapeutic effects on pharyngitis mainly through an antibiotic effect and downregulation of NF-κB signalling pathway.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 459
Author(s):  
Guiqiu Zhang ◽  
Kaijing Guo ◽  
Pengfei Wang ◽  
Yingbo Shan ◽  
Chen Ma

Ilaprazole is a proton pump inhibitor used to treat digestive diseases. In this study, blood samples were collected after oral administration of ilaprazole and prepared by liquid–liquid extraction. The metabolites of ilaprazole were detected by liquid chromatography–high-resolution mass spectrometry (LC-HRMS) and LC-MSn. A total of twelve in vivo metabolites were detected in rat plasma and six new metabolites of ilaprazole, including one reductive metabolite with sulfide (M3), two hydroxylated metabolites with sulfoxide (M7 and M8), and three oxidative metabolites with sulfone (M9, M11, and M12), were identified. The possible metabolic pathways of ilaprazole and the fragmentation behaviors of its metabolites were elucidated. The result of the in silico prediction indicates that all the new metabolites showed the potential ability to inhibit H+/K+-ATPase activity.


2017 ◽  
Vol 41 (8) ◽  
pp. 688-697 ◽  
Author(s):  
Camilla Montesano ◽  
Gabriele Vannutelli ◽  
Federico Fanti ◽  
Flaminia Vincenti ◽  
Adolfo Gregori ◽  
...  

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e83708 ◽  
Author(s):  
Shuai Chen ◽  
Garrett J. McKinney ◽  
Krista M. Nichols ◽  
Maria S. Sepúlveda

2016 ◽  
Vol 133 ◽  
pp. 202-210 ◽  
Author(s):  
Paolo Cocci ◽  
Matteo Mozzicafreddo ◽  
Mauro Angeletti ◽  
Gilberto Mosconi ◽  
Francesco Alessandro Palermo

2009 ◽  
Vol 189 ◽  
pp. S258 ◽  
Author(s):  
Thomas Steger-Hartmann ◽  
Francois Pognan ◽  
Ferran Sanz ◽  
Carlos Acedo Diaz

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