OBJECTIVEPsoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptor γt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity.

METHODUsing molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay.

RESULTMolecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt; bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner.

CONCLUSIONDhd can selectively suppress RORγt transcriptional activity.

Digoxin ; analogs & derivatives ; pharmacology ; Humans ; Models, Chemical ; Molecular Docking Simulation ; Nuclear Receptor Subfamily 1, Group F, Member 1 ; antagonists & inhibitors ; genetics ; Transcription, Genetic

Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptorγt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. Method Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay. Result Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt;bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. Conclusion Dhd can selectively suppress RORγt transcriptional activity.

Objetive Psoriasis is an autoimmune-related chronic inflammatory skin disease strongly associated with the dysfunction of Th17 cells. Retinoic acid-related orphan nuclear receptorγt (RORγt) plays a critical role in the differentiation and maturation of Th17 cells and in cell-derived immunologic derangement. We conducted this study to investigate potential mechanism by which the derivative of digoxin selectively antagonizes RORγt transcriptional activity. Method Using molecular docking in combination with molecular electrostatic potential (MEP), we detected the interaction between the derivative of digoxin (Dhd) and ROR transcription factor (RORα,RORβ and RORγt), and the results were further confirmed by bioluminescent assay. Result Molecular docking demonstrated that Dhd could exclusively inhibit the conformation of RORγt;bioluminescent assay further indicated that RORγt was selectively antagonized by Dhd in a dose- and time-dependent manner. Conclusion Dhd can selectively suppress RORγt transcriptional activity.

Objective To establish the quality representation and correlation analysis method and the content of characteristic ingredients based on spectrum of medicinal system of Juemingzi (Semen Cassiae),in order to evaluate the quality of Semen Cassiae decocting pieces effectively and accurately. Methods HPLC-PDA method was established to characterize the quality of spectrum of Semen Cassiae medicinal system architecture;quality of 11 batches of Semen Cassiae decocting pieces was characterized based on the number and chemical type of peaks on characteristic spectrum. The content of 6 characteristic index components, naphthopyrones and anthraquinones were characterized by indexes in characteristic spectrum. Correlation analysis of quality of Semen Cassiae was then performed with reference to the standard reference pieces. Results Taken as the reference substance, characteristic spectrum of batch 10 Semen Cassiae altogether contains 12 characteristic peaks, all characteristic peaks appeared on the chromatograms of 11 batches of Semen Cassiae. In 11 batches of Semen Cassiae, No.5, 11, 8, 1, 2 pieces contained higher effective index components, while No. 5, 11, 2, 9, and 7 pieces had high relevance with the reference piece (No. 10). Consolidated quality characterization and correlation analysis,the quality of No. 5,11,8,1,2,9,and 7 were excellent and dominant. Conclusion The HPLC method to analyze quality and quantity of phenolic components spectrum of 11 batches of Semen Cassiae is simple and accurate. The evaluation mode of quantity and quality and their correalation based on Semen Cassiae medical system, including systemic correlation and appilication validity, as it can provide a reliable methodological basis for the comprehensive quality evaluation of Semen Cassiae.