Caelastrol and pristimerin derived from Leigongteng inhibit promoter activity of HLA-B~*2705 gene / 中国病理生理杂志

ABSTRACT

AIM:To screen the effective chemicals,which can suppress the promoter activity of the HLA-B2705 gene as potential therapeutic agents.METHODS:The HeLa-HLA-B27,293T-HLA-B27 stable transfectants were used to monitor the effect of 12 264 chemicals through high throughput screening(HTS).Chemicals which regulates HLA-B*2705 promoter activity more than 150% or less than 60% were picked out for the further IC50/EC50 and cell viability detection.RESULTS:(1)The primary screening used by 293T-HLA-B27 stable transfectant yielded about 5.1% hits which either suppressed(556 chemicals)or enhanced(68 chemicals)the HLA-B*2705 promoter activity.(2)A reconfirmation screening was carried out with these 624 of the candidates using transfected HeLa-HLA-B27 cells.Seventy hits were confirmed.(3)Based on the bioinformatics of those positive hits,40 chemicals were selected for in-depth analysis by dose-response experiment and IC50/EC50 detection.Six suppressors showed potential pharmacological activities.Interestingly,two suppressors(celastrol and pristimerin)are derived from Leigongteng,a herbal medicine already used for several decades for treatment of immune regulatory and inflammatory diseases.Four active chemicals were computer designed with no relevance to the above structures.CONCLUSION:Chinese traditional herb Nansheteng and Leigongteng might be the potential drugs for HLA-B27 positive patients.These results provide new direction for research in both the therapeutics and the pathogenesis of spondyloarthritis.