Triterpene glycosides from the aerial parts of Elsholtzia penduliflora W. W. Smith and their cytotoxic activity.

Bio-guided fractionation of the 80% ethanol extract of the aerial parts of Elsholtzia penduliflora W. W. Smith (Lamiaceae) led to the isolation of seven new triterpene glycosides, i.e., pendulosides A-G (1-7), and one known compound (8). Their structures were determined based on extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, and the results of hydrolytic cleavage. Compounds 1, 3-5, and 7-8 were tested for cytotoxic activity against two human cancer cell lines in vitro using the MTT assay method. Among them, two compounds (3 and 7) displayed significant cytotoxicities against human lung cancer (A549) cells with IC50 values of 9.01 ± 1.52 µM and 6.18 ± 1.06 µM, respectively, and human breast cancer (MCF-7) cells with IC50 values of 10.98 ± 1.76 µM and 6.82 ± 1.09 µM, respectively. The results suggest that compounds 3 and 7 might be useful for the therapeutic study of cancer.

Poligapolide, a PI3K/Akt inhibitor in immunodeficiency virus type 1 TAT-transduced CHME5 cells, isolated from the rhizome of Polygala tenuifolia.

The rhizome of Polygala tenuifolia WILLD (PT, family Polygalaceae) has been used in traditional Chinese medicine for inflammation, dementia, amnesia, neurasthenia and cancer. The phosphoinositide 3-kinase (PI3K)/Akt inhibitor(s) was isolated from PT by using the cytoprotective phenotype of human immunodeficiency virus type 1 (HIV-1) Tat-transduced CHME5 cells against lipopolysaccharide/cycloheximide. We isolated 9 constituents (1)-(9) from ethyl acetate fraction of PT, which potently showed anti-cytoprotective effect against HIV-1 TAT-transduced cells. Of them, (9R)-(-)-9-peptandecanolide (2), a new compound named poligapolide, most potently abolished the cytoprotective effect of HIV-1 Tat-transduced CHME5 cells. The compound (2) inhibited the phosphorylation of Akt and its downstream molecule, glycogen synthase kinase-3 beta (GSK3ß) in PI3K/Akt cell survival signaling pathway, but did not suppress the phosphorylation of PI3K and pyruvate dehydrogenase lipoamide kinase isozyme 1. Based on these finding, poligapolide may abolish the cytoprotective phenotype of HIV-1 Tat-transduced CHME5 cells by inhibiting Akt phosphorylation in PI3K/Akt pathway.

Clionosterol and ethyl cholestan-22-enol isolated from the rhizome of Polygala tenuifolia inhibit phosphatidylinositol 3-kinase/Akt pathway.

Phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors were isolated from the rhizome of Polygala tenuifolia WILLD (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-ß-D-glucosyl ethyl cholestan-22-enol (3), and 3-O-ß-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)3ß, 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.