Lignan Glucosides Research Articles

α-Keto tetrahydrofuran lignan glucosides from the Bangladeshi medicinal plant Terminalia citrina inhibit estradiol (E2) induced proliferation in cancer cells

EtOAc extract from the leaves of Terminalia citrina collected in Bangladesh were separated, and seven previously undescribed α-keto tetrahydrofuran lignan glucosides (terminalosides Q to W) were isolated and characterized. NOESY analysis of 1H NMR spectra and ECD spectroscopic data analysis revealed the absolute stereochemistry of the tetrahydrofuran ring of the isolated constituents as being a (7S,8R,8′S)- configuration in terminalosides Q to U and a (7R,8R,8′S)- configuration in terminalosides V and W. All of the isolated compounds were evaluated for their estrogenic and anti-estrogenic properties using two types of estrogen-responsive human breast cancer cell lines (MCF-7 and T47D). Terminaloside R, which has a dioxymethylene group in its aromatic ring, inhibited 90% of estradiol-enhanced cell proliferation in T47D and MCF-7 cells at concentrations of 0.01 μM and 0.1 μM, respectively. On the other hand, terminaloside T, the analogous compound which has two oxymethyl groups in place of dioxymethylene, suppressed 90% of cell proliferation selectively in T47D cells at a concentration of 0.01 μM. However, terminaloside W, the 7R-stereoisomer of terminaloside R, only showed moderate activity.

A New Lignan Glucoside from Cyclea racemosa

A new lignan glucoside 1, along with two known lignans (2, 3), was isolated from Cyclea racemosa Oliv. Its structure was elucidated as (+)-7′-methoxylariciresinol 4-O-β-D-glucopyranoside on the basis of extensive spectroscopic analyses.

A New Insecticidal Lignan Glucoside from Galium verum

A new lignan glucoside, galiveroside A (1), and seven known compounds (2–8), were isolated from Galium verum L. The structure of 1 was elucidated on the basis of extensive spectroscopic analyses. Compound 1, at the concentration of 5 mg/mL, showed insecticide activity to 3 age cotton bollworm with a mortality of 16.3% through stomach poisoning. When combined with a recombinant scorpion toxin rLqh IT-1, a better stomach toxicity was shown, and the corrected mortality rate increased to 36.6%.

Structures of minor glucosides from the Far Eastern high-mountain endemic plant Ligularia alticola Worosch. Screening of bioactivity for some glycosides from L. alticola

Two new minor eremophilane-type sesquiterpene glucosides, alticolosides H (1) and I (2) along with known earlier lignan glucosides (−)-pinoresinol-4′-O-β-d-glucoside, plucheoside D1 and tortoside F were isolated from aerial parts of the endemic Far Eastern species Ligularia alticola Worosch. (Family Asteraceae). Structures of the glycosides were elucidated by 2D NMR spectroscopy and HRESIMS. The absolute stereochemistry of 1 and 2 was determined by comparison of experimental and calculated ECD spectra. The screening of biological activities of the compounds earlier found in L. alticola including the influence on the biofilm formation by Yersinia pseudotuberculosis, cytotoxic activities against different cancer cell lines and the ability to reduce ROS levels in the macrophages pre-stimulated with pro-inflammatory LPS from E. coli was carried out.

Furofuran lignan glucosides from the leaves of Vitex negundo var. cannabifolia

Two new furofuran lignan glucosides, cannabilignin (1) and isocannabilignin (2), together with four known compounds (3–6), were isolated from the leaves of Vitex negundo var. cannabifolia. The structures of the isolates were elucidated by analysis of spectroscopic data. Compound 3 exhibited weak inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 69.1 ± 5.8 μM.

Acyl flavone and lignan glucosides from Leontopodium leontopodioides

Two new acyl flavone glucosides, luteolin-4⿲-O-(6-p-hydroxybenzoyl)-β-d-glucopyranoside (leontopodioside A, 1) and luteolin-4⿲-O-[6-(2-methylbutyryl)]-β-d-glucopyranoside (leontopodioside B, 2), and a new acyl lignan glucoside, lariciresinol-9-angeloyl-4-O-β-d-glucopyranoside (leontopodiosideC, 3) were isolated from the whole plants of Leontopodium leontopodioides (Asteraceae). Their structures were determined by spectroscopic and chemical methods. Compounds 1⿿3 exhibited α-glucosidase inhibitory activity with the half maximal inhibitory concentration (IC50) values of 55.6, 39.7, and 474.9μM, respectively, in comparison with acarbose (626.3μM).

Five furofuranone lignan glucosides from Terminalia citrina inhibit in vitro E2-enhanced breast cancer cell proliferation

Five new polyalkoxylated furofuranone lignan glucosides, terminalosides L–P (1–5), were isolated from EtOAc extracts of the leaves of Terminalia citrina, a Bangladeshi medicinal plant. The structures of the isolates were deduced primarily by NMR spectroscopy, and four of the isolates were found to contain rare tetraoxygenated aryl groups in their structures. The absolute configurations and conformations of the furofuranone ring were confirmed by ECD spectroscopy. All of the isolates were evaluated for their estrogenic and/or antiestrogenic properties using two estrogen responsive breast cancer cell lines, T47D and MCF-7. At a concentration of 10nM, terminaloside L (1) suppressed E2-enhanced T47D cell proliferation by 90%, while terminaloside M (2) showed 90% antiestrogenic activity against MCF-7 cells. Compared to 2, the antiestrogenic activity of terminaloside O (4) and P (5) was weak, possibly due to the different attachment positions of the sugar moiety that they share in common. This is the first report of furofuranone lignans from any Terminalia species, and also of their antiestrogenic activity.

Lignan Glucosides from the Stem Barks of Illicium difengpi.

In this study, four new lignan glucosides, named difengpiosides A–D (1–4), were isolated from the stem barks of Illicium difengpi, together with seven known compounds 5–11. Their structures were identified on the basis of spectroscopic analyses (1D and 2D NMR, HRESIMS, CD) and a comparison with literature data. All the compounds were evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells.

Furofuran Lignan Glucosides with Estrogen-Inhibitory Properties from the Bangladeshi Medicinal Plant Terminalia citrina.

Extracts from the leaves of the Bangladeshi medicinal plant Terminalia citrina were prepared, and 13 new furofuran lignan glucosides, terminalosides A-K (1-4, 6-12), 2-epiterminaloside D (5), and 6-epiterminaloside K (13), were characterized using various spectroscopic techniques. Twelve of the isolates were found to contain rare tetraoxygenated aryl groups in their structures. Analysis of the NMR chemical shifts for the oxymethine signals in the furofuran ring suggested a pragmatic approach to determining the relative configuration of these compounds. The ECD and NOESY spectroscopic data obtained allowed for the deduction of the absolute configurations and conformations of the compounds. The isolates were tested for their estrogenic/antiestrogenic activity using the MCF-7 and T47D estrogen-responsive human breast cancer cell lines. Terminalosides B (2) and G (8) exhibited inhibitory effects for both cell lines, and estradiol-enhanced cell proliferation was suppressed by 90% at concentrations lower than 10 μM. Terminaloside E (6) showed inhibitory activity against the T47D cell line, whereas terminalosides C (3), F (7), and I (10) and 6-epiterminaloside K (13) displayed antiestrogenic activity against MCF-7 cells.

Three new lignan glucosides from the roots of Scutellaria baicalensis

Three new lignan glucosides, baicalensinosides A–C (1–3), were isolated from the roots of Scutellaria baicalensis. The structural elucidation was achieved by in-depth spectroscopic examinations and qualitative chemical test. Structurally, these compounds belong to the 3,4-dibenzyltetrahydrofuran-type lignan glycoside with a mono-hydroxyl substitution at the 7′-position of benzylidene group on the numbering system of lignans being one of their shared critical features. The anti-osteoporotic activity of the isolated compounds was assessed in an in vitro osteoprotegerin (OPG) transcriptional activity assay using dual luciferase reporter detection. At 10μmol/L, compounds 1–3 increased the relative activating ratio of OPG transcription to 1.83, 0.84 and 0.98 times that of the control group, respectively.

Officinalioside, a new lignan glucoside from Borago officinalis L.

A new lignan glucoside, officinalioside (1), was isolated from n-BuOH fraction of the aerial parts of Borago officinalis L., together with four known compounds: actinidioionoside (2), roseoside (3), crotalionoside C (4) and kaempferol 3-O-β-D-galactopyranoside (5). The structure of the new compound was established by means of spectroscopic and chemical analyses. Compounds 1 and 2 showed a moderate DPPH radical scavenging activity (IC50: 52.6 ± 1.70 and 41.3 ± 0.25 μM, respectively) comparable with that of the standard trolox (16.6 ± 2.2 μM) without any significant cytotoxicity towards human cell line A549 (IC50 > 100 μM).

Schisandrosides A-D, Dibenzocyclooctadiene Lignan Glucosides from the Roots of Schisandra chinensis.

Four new dibenzocyclooctadiene lignan glucosides, schisandrosides A-D (1-4), as well as two known rare nortriterpenoids, micrandilactone C (5) and propindilactone Q (6), were isolated from the roots of Schisandra chinensis BAILLON (Schisandraceae). The structure of compounds 1-4 were elucidated by physical and spectroscopic data interpretation. To the best of our knowledge, schisandrosides A-D (1-4) represent the first example of a dibenzocyclooctadiene lignan glycoside.

Hepatoprotective activity of twelve novel 7'-hydroxy lignan glucosides from Arctii Fructus.

Twelve novel 7'-hydroxy lignan glucosides (1-12), including two benzofuran-type neolignans, two 8-O-4' neolignans, two dibenzylbutyrolactone lignans, and six tetrahydrofuranoid lignans, together with six known lignan glucosides (13-18), were isolated from the fruit of Arctium lappa L. (Asteraceae), commonly known as Arctii Fructus. Their structures were elucidated using spectroscopy (1D and 2D NMR, MS, IR, ORD, and UV) and on the basis of chemical evidence. The absolute configurations of compounds 1-12 were confirmed using rotating frame nuclear overhauser effect spectroscopy (ROESY), the circular dichroic (CD) exciton chirality method, and Rh2(OCOCF3)4-induced CD spectrum analysis. All of the isolated compounds were tested for hepatoprotective effects against D-galactosamine-induced cytotoxicity in HL-7702 hepatic cells. Compounds 1, 2, 7-12, and 17 showed significantly stronger hepatoprotective activity than the positive control bicyclol at a concentration of 1 × 10(-5) M.

Caragiside D, a New Isoflavone Glucoside from Caragana conferta

Caragiside D (1), a new isoflavone glucoside, has been isolated from the n-BuOH soluble subfraction of the MeOH soluble extract of the whole plant of Caragana conferta along with one known isoflavone glucoside, caragiside A (2), and two lignan glucosides, pinoresinol 4-O-glucoside (3) and syringaresinol 4-O-glucoside (4). The structures of these compounds were elucidated through spectroscopic techniques including MS and 2D NMR. The purity of compound 1 was confirmed by HPLC.

Brachysides A and B, New Lignan Glucosides from Caragana Brachyantha

Brachysides A and B, new lignan glucosides, have been isolated from the n-butanol soluble fraction of Caragana brachyantha, along with four known lignan glucosides, acanthoside B, tortoside B, lariciresinol 4'- O-β-D-glucopyranoside and pinoresinol 4,4'-di-O-β-D-glucopyranoside, reported for the first time from the genus Caragana. Antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay.

Lyoniresinol 3α-O-β-D-Glucopyranoside-Mediated Hypoglycaemia and Its Influence on Apoptosis-Regulatory Protein Expression in the Injured Kidneys of Streptozotocin-Induced Mice

Averrhoa carambola L. (Oxalidaceae) root (ACLR) has a long history of use in traditional Chinese medicine for treating diabetes and diabetic nephropathy (DN). (±)-Lyoniresinol 3α-O-β-D-glucopyranoside (LGP1, LGP2) were two chiral lignan glucosides that were isolated from the ACLR. The purpose of this study was to investigate the effect of LGP1 and LGP2-mediated hypoglycaemia on renal injury in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were administrated LGP1 and LGP2 orally (20, 40, 80 mg/kg body weight/d) for 14 days. Hyperglycaemia and the expression of related proteins such as nuclear factor-κB (NF-κB), caspase-3, -8, -9, and Bcl-associated X protein (Bax) were markedly decreased by LGP1 treatment. However, LGP2 treatment had no hypoglycaemic activity. Diabetes-dependent alterations in the kidney such as glomerular hypertrophy, excessive extracellular matrix amassing, and glomerular and tubular basement membrane thickening were improved after 14 days of LGP1 treatment. B cell lymphoma Leukaemia-2 (Bcl-2) expression was reduced in the STZ-induced diabetic mouse kidneys but was enhanced by LGP1 treatment. These findings suggest that LGP1 treatment may inhibit diabetic nephropathy progression and may regulate several pharmacological targets for treating or preventing diabetic nephropathy.

Lignan Glucosides fromSinomenium acutumRhizomes

The new lignan glucoside, acutumoside (1), was isolated from Sinomenium acutum rhizomes together with nine known compounds (2-10). The structure of 1 was elucidated on the basis of extensive spectroscopic analyses, including two-dimensional nuclear magnetic resonance and chemical reactions. Compounds 2, 7, 8, and 10 displayed potential antiproliferative activity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines, while compound 1 showed weak activity against these human tumor cells.

Isolation of new flavan-3-ol and lignan glucoside from Loropetalum chinense and their antimicrobial activities

Phytochemical and antimicrobial activity study on the ethanol extract of the leaves and stems of Loropetalum chinense led to the isolation of a new flavan-3-ol compounds, 8-[1-(3,4-dihydroxyphenyl)-3-methoxy-3-oxopropyl]-catechin (loropetaliside A) (1) and a new lignan glucoside, 1-(5-hydroxy-3-methoxyphenyl)-2-(2-β-glucopyranosyl-4-hydroxy-5-(1-(E)propen-3-ol)-phenyl)-propane-3-ol (loropetaliside B) (3) and several known compounds manglieside D (2), quercetin (4), kaempferol-3-O-D-glucopyranoside (5), quercetin-3-O-β-L-rhamnoside (6) and tiliroside (7). Their structures were elucidated on the basis of extensive spectroscopic analysis.

Phytochemical constituents of Mongolian traditional medicinal plants, Chamaerhodos erecta and C. altaica, and its constituents prevents the extracellular matrix degradation factors

Activity-guided isolation of the n-butanol fraction of Chamaerhodos erecta and water soluble fraction of C. altaica resulted in the isolation of 39 compounds, including new compounds identified as 4,5-dihydroxybenzaldehyde-3-O-β-D-glucopyranoside (1) from C. erecta and quercetin-3-O-β-D-glucuronopyranosyl-4'-O-β-D-glucopyranoside (2) from C. altaica. A total of 37 other compounds were identified based on physico-chemical properties and spectroscopic data. Antioxidative activity was evaluated using a DPPH radical-scavenging method, hyaluronidase inhibitory activity, and advanced glycation end products production inhibitory activity of isolated compounds. Some flavonols (4, 6, 9-11, 14, 15), catechins (18, 19), an amino acid (20), a lignan glucoside (23), and tannins (29-39) exhibited potential a free radical scavenging activity while the new compound (1) showed weak activity. A catechin (18) and some of the tannins (32, 33, 35, 36, 38) had moderate hyaluronidase inhibitory activity. Some of flavonoids and tannins prevented advanced glycation end products production, and the IC₅₀ of compounds 3, 9, 14-16, 33, 34, 36, 38, and 39 were determined.

Root tubers of Lactuca tuberosa as a source of antioxidant phenolic compounds and new furofuran lignans

From the root tubers of Lactuca tuberosa, a wild edible plant species, nine phenolic compounds were isolated, including two new furofuran lignan glucosides, named lactuberin A and lactuberin B. Their structures were elucidated by spectroscopic methods, especially HRESIMS and 2D NMR techniques. This is the first time that compounds belonging to the epi series of 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane type furofuran lignans have been found in Lactuca species. The total phenolic content of the root tuber extract was evaluated and its major phenolic constituents, caffeic acid, chlorogenic acid and 3,5 dicaffeoylquinic acid, known to possess antioxidant activity, were quantified. Additionally, the root tuber extract showed DPPH radical scavenging activity implying its potential as functional food.