Butanolides and clerodane diterpenes from the twigs of Casearia grewiifolia and their effects on adiponectin secretion

Abstract

Three butanolides derivatives, grewiifolides A-C, and nine clerodane diterpenes, grewiifolins M-U, as well as a known sterol were isolated from the twigs of Casearia grewiifolia. The chemical structures and configurations of all isolates were established by various spectroscopic means and chemical derivatization. In a cell-based phenotypic assay using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs), grewiifolide B significantly promoted adiponectin-secretion with EC50 value of 24.8 mu M. In target identification studies, butanolide derivatives were selectively bound to PPAR gamma with Ki values of 4.65, 0.55, and 17.8 mu M, respectively. Further functional analysis and molecular modeling revealed that grewiifolide B promotes adiponectin-secretion through PPAR gamma full agonism.