Shikonin Binds and Represses PPARγ Activity by Releasing Coactivators and Modulating Histone Methylation Codes.

ABSTRACT: Shikonin, a natural ingredient produced by Lithospermum erythrorhizon, has anti-inflammatory, anti-cancer, and anti-obesity effects. It also inhibits adipocyte differentiation; however, the underlying molecular and epigenetic mechanisms remain unclear. We performed RNA-sequencing of shikonin-treated 3T3-L1 cells. Gene ontology and gene set enrichment analysis showed that shikonin is significantly associated with genes related to adipogenesis, histone modification, and PPARγ. Shikonin treatment downregulated the mRNA expression of PPARγ-responsive genes and rosiglitazone-induced transcriptional activity of PPARγ. Microscale thermophoresis assays showed a K_D value 1.4 ± 0.13 μM for binding between shikonin and PPARγ. Glutathione S-transferase pull-down assays exhibited that

SUBMITTER: Park UH 

PROVIDER: S-EPMC10097191 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature