Inokosterone Is a Potential Drug Target of Estrogen Receptor 1 in Rheumatoid Arthritis Patients:Analysis from Active Ingredient of Cyathula Officinalis

Objective:To elucidate the active compounds and the molecular mechanism of Cyathula Off/c/na//s as a drug treatment for rheumatoid arthritis(RA).Methods:The target genes of active ingredients from Cyathula Officinalis were obtained from bioinformatics analysis tool for the molecular mechanism of traditional Chinese medicine.The protein-protein interaction between the target genes were analyzed using STRING and Genemania.The transcriptome of RA patients compared to healthy people(GSE121894)were analyzed using R program package Limma.The relative expression of the target genes was obtained from the RNA-seq datasets.The molecular docking analyses were processed based on the molecular model of estrogen receptor 1(ESR1)binding with estradiol(PDB ID:1A52).The binding details were analyzed by SYBYL.Results:Inokosterone,ecdysterone,and cyaterone were the 3 active ingredients from Cyathula Officinalis that bind to target genes.Of all the significantly changed genes from RA patients,ESR1,ADORA1,and ANXA1 were significantly increased in mRNA samples of RA patients.Conclusion:ESR1,the transcription factor that binds inokosterone in the molecular binding analysis,is the target protein of Cyathula Officinalis.