Dipasperoside A, a Novel Pyridine Alkaloid-Coupled Iridoid Glucoside from the Roots of <i>Dipsacus asper</i>

Abstract

A new pyridine alkaloid-coupled iridoid glucoside, dipasperoside A (1), and 20 known compounds (2-21) were isolated from a water extract of Dipsacus asper roots. Compound 1 possessed a unique structural feature with a nicotinic acid nucleus coupled through C-5 with C-7 of a secoiridoid/iridoid glucoside dimer, and esterified with a C-7 hydroxyl group of an iridoid glucoside monomer. All isolates were evaluated for their inhibitory activity against nitric oxide (NO) production in a lipopolysaccharide (LPS)-activated murine macrophage cell line, RAW264.7.

Anticancer Effect of the Iridoid Glycoside Fraction from Dipsacus fullonum L. Leaves

“…The second major peak obtained for fraction 9-11 (compound 2) was identified as sylvestroside III-(IV) diethyl acetal, with the molecular formula C 31…”

“…[23][24][25][26][27][28] To date, about 30 iridoids have been isolated from D. asper, D. laciniatus, D. fullonum, D. japonicus, and D. ferox, 16,29 but their cytotoxic effect has been evaluated by only a few researchers. 30,31 The wide distribution and remarkable pharmacological activities of Dipsacus species indicate their potential for the discovery and development of new natural drugs. Previously, the leaves and root extract of D. fullonum were investigated only for the inhibition of α-amylase, 32 while the descriptions of its therapeutic properties can mostly be found in encyclopedias.…”

A New Monoterpenoid Glucoindole Alkaloid From Dipsacus asper

“…These activities are very similar to that of the positive control L-NMMA (22.6 µM), a non-selective NO synthase (NOS) inhibitor, 19 but weaker than those of dipasperoside A (IC 50 = 15.2 µM) and akebia saponin D (IC 50 = 12.7 µM), both of which are obtained from the water extract of D. asper roots. 14,15 Furthermore, an MTT assay revealed that compounds 1 and 2 exhibit no significant cytotoxicity against LPS-activated macrophage RAW264.7 cells at concentrations of up to 50 µM.…”

“…12,13 In a previous study on the anti-inflammatory constituents of traditional medicinal plants, we analyzed the water extract of D. asper roots, which showed significant half-maximal inhibitory activity (IC 50 = 45.1 µg/mL) against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells. Through bioassay-guided fractionation of the water extract, we isolated a new pyridine alkaloid-coupled iridoid glucoside (dipasperoside A), a new trisiridoid glucoside (dipasperoside B), and a known monoterpene indole alkaloid (3β,5α-tetrahydrodesoxycordifoline lactam), as well as 8 known iridoids (cantleyoside, dipsanosides A and B, loganic acid, loganin, sweroside, sylvestroside I, triplostoside A), 4 phenolics (3,4-dihydroxybenzaldehyde, 3,4-dihydroxybenzoic acid, caffeic acid, and vanillic acid), 3 known quinic acid derivatives (3,4- 14,15 Thereafter, we analyzed their NO production inhibitory activity against LPS-activated RAW264.7 cells and identified dipasperoside A (IC 50 = 15.2 µM) and akebia saponin D (IC 50 = 12.7 µM) as active constituents. 14 In the present study, as part of our ongoing phytochemical investigation of this plant, we isolated 2 monoterpenoid glucoindole alkaloids from the methanol (MeOH) extract of D. asper roots and identified therein a new alkaloid, (3R,5S)-5carboxyvincosidic acid 22-loganin ester (1), and the known alkaloid, (3S,5S)-5-carboxystrictosidic acid 22-loganin ester (dipsaperine 16 ) (2) (Figure 1).…”

Dipasperoside B, a New Trisiridoid Glucoside from Dipsacus asper

“…In our screening for the anti-inflammatory activity of traditional medicinal plants, we found that a water extract of D. asper roots showed significant inhibitory activity against the production of NO in LPS-activated murine macrophage RAW264.7 cells (IC 50 , 45.1 μg/mL). Through bioassay-guided fractionation, we isolated 21 compounds including a new pyridine alkaloid-coupled iridoid glucoside, dipasperoside A, and identified dipasperoside A (IC 50 , 15.2 μM) and akebia saponin D (IC 50 , 12.7 μM) as active constituents [14]. In a continuing study, we recently isolated a new iridoid glucoside trimer named dipasperoside B (1).…”