Phenylethanoid Glycosides from Digitalis purpurea and Penstemon linarioides with PKCα-Inhibitory Activity

Abstract

In a continuation of our search for potential tumor inhibitors from plants, it was found that the CH2Cl2-MeOH (1:1) extracts from Digitalis purpurea and Penstemon linarioides both showed PKCalpha-inhibitory bioactivity. Bioassay-directed fractionation of the extract from D. purpurea yielded the new, weakly active phenylethanoid glycoside 2-(3-hydroxy-4-methoxy-phenyl)-ethyl-O-(alpha-L-rhamnosyl)-(1-->3) -O- (alpha-L-rhamnosyl)-(1-->6)-4-O-E-feruloyl-beta-D-glucopy ran oside (1) together with the four known compounds calceolarioside A (2), calceolarioside B (3), forsythiaside (4), and plantainoside D (5). The extract from P. linarioides yielded the three known glycosides leucosceptoside A (6), acteoside (7), and poliumoside (8), together with the iridoid plantarenaloside (9). All of the isolated compounds, except compound 9, showed inhibitory activity against PKCalpha with IC50 values (in microM) of 125 (1), 0.6 (2), 4.6 (3), 1.9 (4), 14.8 (5), 19.0 (6), 9.3 (7), and 24.4 (8).

A new phenylethanoid glycoside from the fruits of Callicarpa japonica Thunb. var. luxurians Rehd.

“…Compounds 2-6 were identified as forsythoside B (2) [5,6], brandioside (3) [7], poliumoside (4) [8], actioside (5) [9], and apigenin 7-galacturonide (6) [10], respectively, based on their spectral and physical data, although the 1 H-and 13 C-NMR spectral data of 6 have not been reported in the literature.…”

An LC-MS/MS method for determination of forsythiaside in rat plasma and application to a pharmacokinetic study

“…Pharmacological studies demonstrated that forsythiaside possesses strong antioxidant [8,9], antibacterial [8] and antiviral [10,11] activities, and also exhibits a slow relaxation effect against norepinephrine induced contraction of rat aorta [12]. Moreover, it is reported that forsythiaside could significantly protect DNA damage caused by hydroxyl radicals [13] and inhibit protein kinase C (PKC␣) with an IC 50 value of 1.9 M [14].…”

Screening of natural compounds and their derivatives as potential protein kinase C inhibitors

“…More than 500 natural and synthetic flavonoids have been shown to inhibit the growth of cancer cell lines [Ló pezLázaro et al, 2002]. The connection between cancer and PKC has stimulated a search for new potential PKC modulators among flavonoids and other natural compounds and products [Ferriola et al, 1989;Agullo et al, 1997;Nick et al, 1995;Mistry et al, 1997;Zhou et al, 1998]. Multiple mechanisms of action have been identified for the antiproliferative and cancer preventive effects of flavonoids [Birt et al, 2001].…”