摘要：Phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors were isolated from the rhizome of Polygala tenuifolia W ILLD (PT, Polygalaceae), which has been used in traditional Chinese medicine for inflammation, dementia, amnesia, neurasthenia and cancer, by activity-guided fractionation. For the assay of PI3K/Akt pathway, cytoprotective Tat-transduced CHME5 cells, which are the cytoprotective phenotype against lypopolysaccharide (LPS)/cycloheximide (CHX), were used. We isolated 4 anti-cytoprotective compounds, clionasterol ( 1 ), ethyl cholestan-22-enol ( 2 ), 3- O -β- D -glucosyl ethyl cholestan-22-enol ( 3 ), and 3- O -β- D -glucopyranosyl clionasterol ( 4 ) from EtOAc fraction of PT against Tat-transduced CHME5 cells. Of them, ( 1 ) and ( 2 ) most potently abolished cytoprotective effect of Tat-transduced CHME5 cells. These constituents ( 1 ) and ( 2 ) inhibited the activation of 3-phosphoinositide-dependent kinase 1 (PDK1) and its downstream molecules, Akt/glycogen synthase kinase (GSK)3β, in PI3K/Akt cell survival signaling pathway, but did not suppress the activation of PI3K. Based on these finding, ( 1 ) and ( 2 ) may abolish the cytoprotective phenotype of Tat-transduced CHME5 cells by inhibiting PDK1 phosphorylation in PI3K/Akt pathway.
