Myocardial fibrosis is a pivotal pathophysiological step of various cardiovascular diseases, which
eventually leads to heart failure and death. Cardiac fibroblasts activation and subsequently differentiate into
myofibroblasts are pivotal pathophysiological step in myocardial fibrosis. Phosphoglycerate mutase 1
(PGAM1) directly interacts with α-smooth muscle actin (ACTA2) and participate in fibrosis regulation.
Allosteric inhibitor of PGAM1 could attenuates fibrosis through break the interaction of PGAM1 and ACTA2.
In this study, we aimed to screen and identify novel ligand of PGAM1 in natural product library. Firstly,
various natural products were screened via DARTS assay and Carthamus tinctorius L. was identified as a target
pool for molecular docking. Then, in silico screening assay identified baicalein as a novel ligand. In addition,
baicalein could directly bind to the PGAM1 protein with a KD value of 34.6 μM. Molecular dynamics
simulation revealed that baicalin and PGAM1 interactions were stable. These findings indicate that PGAM1 is
a direct pharmacological target of baicalein. Immunoblot analysis further demonstrated that baicalin inhibits
the activation of fibroblasts in vitro. Finally, the anti-myocardial fibrosis effect of baicalein was verified in vivo.
Taken together, our findings suggest that baicalein is a novel PGAM1 templates for developing new
therapeutics against myocardial fibrosis.
