Six New Polyhydroxysteroidal Glycosides,Anthenosides S1 – S6, from the Starfish Anthenea sibogae

Six new polyhydroxysteroidal glycosides, anthenosides S1  –  S6 ( 1  –  6 ), along with a mixture of two previously known related glycosides, 7 and 8 , were isolated from the methanolic extract of the starfish Anthenea sibogae. The structures of 1  –  6 were established by NMR and HR‐ESI‐MS techniques as well as by chemical transformations. All new compounds have a 5α‐cholest‐8(14)‐ene‐3α,6β,7β,16α‐tetrahydroxysteroidal nucleus and differ from majority of starfish glycosides in positions of carbohydrate moieties at C(7) and C(16) ( 1  –  4 , 6 ) or only at C(16) ( 5 ). The 4‐O‐methyl‐β‐d ‐glucopyranose residue ( 2 ) and Δ²⁴‐cholestane side chain ( 3 ) have not been found earlier in the starfish steroidal glycosides. The mixture of 7 and 8 slightly inhibited the proliferation of human breast cancer T‐47D cells and decreased the colony size in the colony formation assay.     

New phenanthrene glycosides from Dendrobium denneanum and their cytotoxic activity

Five new phenanthrene glycosides, denneanosides A–E (1–5), and one new 9,10-dihydrophenanthrene glycoside, denneanoside F (6) were isolated from the stem of Dendrobium denneanum. The chemical structures of the new compounds were established on the basis of extensive spectroscopic data. The isolated compounds were evaluated for their in vitro cytotoxic activity against SNU387 hepatocellular carcinoma cell line. Compounds 1–3 showed moderate cytotoxic activities while compounds 4–6 showed weak activities.     

Structures of the novel diterpene glycosides from Stevia rebaudiana

From the commercial extract of the leaves of Stevia rebaudiana, two new diterpenoid glycosides were isolated besides the known steviol glycosides including stevioside, rebaudiosides A–F, rubusoside, and dulcoside A. The structures of the two new compounds were identified as 13-[(2-O-6-deoxy-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (1), and 13-[(2-O-6-deoxy-β-d-glucopyranosyl-3-O-β-d-glucopyranosyl-β-d-glucopyranosyl)oxy] ent-kaur-16-en-19-oic acid β-d-glucopyranosyl ester (2), on the basis of extensive NMR and MS spectral data as well as chemical studies.     

Novel Secoiridoid Glucosides in Olea europaea Leaves Suffering from Boron Deficiency

From the methanol extract of boron deficient Olea europaea leaves, two secoiridoid glycosides, not detected in leaf extracts of untreated plants, 6′-E-p-coumaroyl-secologanoside and 6′-O-[(2E)-2,6-dimethyl-8-hydroxy-2-octenoyloxy]-secologanoside, were isolated together with three known secoiridoid glycosides, oleuropein, oleoside dimethyl ester, and secologanoside. The structures of the isolated compounds were established by means of NMR and MS spectral analyses. The above novel secoiridoids were synthesized by the plant as a physiological response to nutrient stress.     

Two new lathyrane-type diterpenoid glycosides with IL-6 production inhibitory activity from the roots of Euphorbia kansui

As part of our ongoing search for anti-inflammatory compounds from higher plants, we isolated and elucidated two new diterpenoid glycosides, kansuingol A (1) and kansuingol B (2), from the roots of Euphorbia kansui. These structures were elucidated by extensive spectroscopic methods such as NMR and MS. Compounds were assessed for their IL-6 production inhibitory activity in PMA?+?A23187-stimulated HMC-1 cells. As a result, compounds 1 and 2 exerted inhibitory activities in the production of IL-6 with IC₅₀ values of 2.96, and 1.94?μM, respectively. Further, kansuingol A (1) decreased mRNA expressions of TNF-α and IL-6.     

Melanogenesis‐Inhibitory Saccharide Fatty Acid Esters and Other Constituents of the Fruits of Morinda citrifolia (Noni)

Five new saccharide fatty acid esters, named nonioside P ( 3 ), nonioside Q ( 4 ), nonioside R ( 8 ), nonioside S ( 10 ), and nonioside T ( 14 ), and one new succinic acid ester, butyl 2‐hydroxysuccinate (=4‐butoxy‐3‐hydroxy‐4‐oxobutanoic acid) ( 31 ), were isolated, along with 26 known compounds, including eight saccharide fatty acid esters, 1, 2, 5, 6, 7, 9, 12 , and 13 , three hemiterpene glycosides, 15, 17 , and 18 , six iridoid glycosides, 21 – 25 , and 27 , and nine other compounds, 20, 28, 29 , and 32 – 37 , from a MeOH extract of the fruit of Morinda citrifolia (noni). Upon evaluation of these and five other glycosidic compounds, 11, 16, 19, 26 , and 30 , from M. citrifolia fruit extract for their inhibitory activities against melanogenesis in B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), most of the saccharide fatty acid esters, hemiterpene glycosides, and iridoid glycosides showed inhibitory effects with no or almost no toxicity to the cells. These compounds were further evaluated with respect to their cytotoxic activities against two human cancer cell lines (HL‐60 and AZ521) and their inhibitory effects on Epstein? Barr virus early antigen (EBV‐EA) activation induced with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cells.     

New lignan glycosides from the root barks of Litsea glutinosa

An investigation on the chemical constituents in the root barks of Litsea glutinosa was performed for the first time. Three new lignan glycosides named Litseasins A–C (1–3), together with a known one (4), were obtained. The structures of the new compounds were established through extensive spectroscopic analyses including HR-ESI–MS, NMR, and circluar dichroism (CD). The new compounds were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induce nitric oxide (NO) production in RAW264.7 murine macrophage cells. However, these compounds showed no inhibition on LPS-induced NO productions.     

Four new glycosides from the seeds of Cassia obtusifolia

Four new glycosides, including one anthraquinone glycoside (1), one naphthalene glycoside (2), and two naphthopyrone glycosides (3–4), with 10 known compounds (5–14) were isolated from the seeds of Cassia obtusifolia L. The new structures were determined by spectroscopic analysis and chemical transformations.     

New Acylated Flavonol Glycosides and a Phenolic Profile of Pritzelago alpina,a Forgotten Edible Alpine Plant

Thirteen acylated flavonoid glycosides, 1 – 13 , including eleven new congeners, 3 – 13 , were isolated from the aerial parts of Pritzelago alpina (Brassicaceae) by a combination of column chromatography on Sephadex LH‐20, and preparative and semi‐preparative HPLC. The structures were established by extensive NMR and MS experiments in combination with acid hydrolysis and sugar analysis by GC/MS. The new compounds were shown to be kaempferol and quercetin glycosides acylated for most of them by a branched short chain fatty acid or a hydroxycinnamic acid residue on the sugar portion. As shown by a HPLC‐DAD analysis of a MeOH extract, these compounds are the main phenolic constituents in the aerial parts of the plant.     

Phytochemical Profiling and Compound Isolation of Cissus rhombifolia Vahl. Leaves Aqueous Methanolic Extract with the Evaluation of Its Anti-Inflammatory Effect Using Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells

The inflammatory disorders represent a serious health issue. Certain Cissus species possess anti-inflammatory effect. Cissus rhombifolia Vahl. leaves’ anti-inflammatory activities and phytoconstituents are poorly characterized. In this study, 38 constituents were tentatively characterized in Cissus rhombifolia Vahl. leaves’ aqueous methanolic extract (CRLE) using high-performance liquid chromatography combined with mass spectrometry (HPLC/MS) and Proton Nuclear Magnetic Resonance (¹H-NMR). Myricetin, β-amyrin, and alliospiroside A, were isolated from CRLE using column chromatography. The anti-inflammatory effect of CRLE and its isolated compounds were studied in lipopolysaccharide (LPS)-induced RAW 264.7 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT assay) was used to assess how CRLE and its isolated compounds affected cell viability. Further, its effects on the production of intracellular NO, and inflammatory cytokines cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) were assessed by the Griess test, and cytokine enzyme-linked immunosorbent assays, respectively. CRLE and its isolated compounds, myricetin, β-amyrin, and alliospiroside A decreased the NO production. Western blotting was performed to assess the protein expression levels of the inflammatory cytokines inducible nitric oxide synthase (iNOS). Alliospiroside A downregulated IL-6, TNF-α, and COX-2 and inhibited the expression of iNOS. CRLE and its compounds represent effective alternative candidate to treat inflammatory diseases.     

Four New Acylated Iridoid Glycosides from the Aerial Part of Veronicastrum sibiricum and Their Antioxidant Response Element‐Inducing Activity

Four new ( 1 – 4 ) and one known ( 5 ) acylated iridoid glycosides were isolated from the aerial parts of Veronicastrum sibiricum (L.) Pennell . The chemical structures of the isolated compounds were determined to be 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosyl‐10‐O‐bergaptol‐5,7‐bisdeoxycynanchoside ( 1 ), 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylpaulownioside ( 2 ), 2″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylcatalpol ( 3 ), 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylaucubin ( 4 ), and 3″,4″‐dicinnamoyl‐6‐O‐rhamnopyranosylcatalpol ( 5 ) using spectroscopic techniques. Among these compounds, compound 5 increased antioxidant response element (ARE) luciferase activity.     

Anti-inflammatory iridoid glycosides from fruits of Cornus officinalis

Three undescribed iridoid glycosides, cyc(7β-O-6′)-morroniside (1), 6′-methyl succinate-7β-O-methylmorroniside (2), and 7β-O-methyl phenyllactate morroniside (3) were isolated from 50% ethanol extract of Cornus officinalis fruits. The structures of the isolated compounds were determined by HRESIMS, ¹D NMR, ²D NMR, UV and IR spectroscopic methods. Compounds 1-3 exhibited moderate anti-inflammatory activities in vivo in a CuSO₄-induced zebrafish inflammation model (when evaluated at 50 μM).     

Tyrosinase Inhibitors from the Aerial Parts of Wulfenia carinthiaca Jacq.

Activity guided isolation of a MeOH extract of the aerial plant parts of Wulfenia carinthiaca Jacq . (Plantaginaceae), using a mushroom tyrosinase assay, resulted in the isolation of five phenylethanoid glucosides and four iridoid glycosides. Two of them, 2′‐O‐acetylisoplantamajoside and 2′,6″‐O‐diacetylisoplantamajoside, represent new natural products. Evaluation of the inhibitory activity of all isolated compounds revealed that the observed activity is not related to the isolated phenylethanoid glycosides but mainly due to the presence of the iridoid glycoside globularin (IC₅₀ 41.94 μm ; CI_95% ± 16.61/11.89 μm ). Interestingly, structurally close related compounds (globularicisin, baldaccioside, and isoscrophularioside) showed no or only a weak tyrosinase inhibitory activity.     

Investigation of chemical constituents from Spiraea prunifolia var. simpliciflora and their biological activities

Quantum mechanics (QM)-based calculations for elucidating full structures of natural compounds are growing in importance and reliability. Two new phenolic glycosides (1 and 2) and 11 known compounds were isolated from the twigs of Spiraea prunifolia var. simpliciflora. The chemical structures of the new compounds (1 and 2) were initially established through different NMR techniques (¹H and ¹³C NMR, COSY, HSQC, and HMBC), HRMS data analysis, and chemical hydrolysis. These structure assignments were further verified by QM-based NMR chemical shift calculations. All of the purified compounds (1–13) were evaluated for their cytotoxicity against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and BT549). Those phytochemicals were also evaluated for both anti-inflammatory activity through the measurement of nitric oxide (NO) production levels in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cell lines and neuroprotective effects via induction of nerve growth factor (NGF) in C6 glioma cells.     

Minor diterpenoid glycosides from the leaves of Stevia rebaudiana

From the commercial extract of the leaves of Stevia rebaudiana, three new diterpenoid glycosides were isolated besides eight known steviol glycosides including stevioside, rebaudiosides A–F and dulcoside A. The structures of the three compounds were identified as 13-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]-kaur-16-en-18-oic acid-(6-O-β-d-xylopyranosyl-β-d-glucopyranosyl) ester (1), 13-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]-17-hydroxy-kaur-15-en-18-oic acid β-d-glucopyranosyl ester (2), and 13-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]-17-oxo-kaur-15-en-18-oic acid β-d-glucopyranosyl ester (3) on the basis of extensive NMR and MS spectral studies. Another known diterpenoid glycoside, 13-[(2-O-β-d-glucopyranosyl-β-d-glucopyranosyl) oxy]-kaur-15-en-18-oic acid β-d-glucopyranosyl ester (4) was also isolated and its complete NMR spectral assignments were made on the basis of COSY, HSQC and HMBC spectral data.     

Further constituents from Caralluma negevensis

Two new megastigmane glycosides (1 and 2) and two new flavone glycosides (3 and 4) were isolated from the methanol extract of the whole plant of Caralluma negevensis Zohary (Asclepiadaceae). The structures of the isolated compounds were characterized as (9R)-2beta,9-dihydroxymegastigma-4,7-dien-3-one-9-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (1), 2beta,9-dihydroxymegastigma-4-en-3-one 9-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (2), luteolin 3'-O-beta-D-glucopyranoside-4'-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (3), and luteolin 3',4'-di-O-beta-D-glucopyranoside (4). The structures of the isolated compounds were established on the basis of spectral evidence and chemical transformation.     

Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria

Eight new cardiac glycosides/aglycones (antiaritoxiosides A–G, 1–7, and antiarotoxinin B, 8), two new coumarins (anticarins A–B, 41–42), and two new flavanones (antiarones L–K, 43–44) were isolated from trunk bark of Antiaris toxicaria together with 53 known compounds. The new structures were established by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3α-hydroxy) and compounds 3–6 (10-hydroxy) contain unique substituents that are rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9, CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all ten cancer cell lines, with notable potency at the ng/mL level against some cell lines, which merits further development as clinical trial candidates.     

New phenolic glycosides isolated from Penthorum chinense Pursh

A phytochemical investigation from 80% ethanol extract of Penthorum chinense Pursh (Saxifragaceae) resulted in the isolation of three new phenolic glycosides (1–3), together with three known phenolic glycosides (4–6). The structures of the new compounds were deduced from their comprehensive spectroscopic analysis including IR, HR-EI-MS, ¹H NMR, ¹³C NMR, DEPT, COSY, HMBC and HMQC. And the structures of known compounds 4–6 were identified by comparison of their spectral data with those reported in the literature.     

Phenolic metabolites from Pyruscalleryana and evaluation of its free radical scavenging activity

Investigation of the aqueous alcoholic extract of Pyruscalleryana Decne. leaves led to the isolation of two new phenolic acids glycosides, namely protocatechuoylcalleryanin-3-O-β-glucopyranoside (1) and 3′-hydroxybenzyl-4-hydroxybenzoate-4′-O-β-glucopyranoside (2), together with nine known compounds among them lanceoloside A and methylgallate, which have been isolated for the first time from the genus Pyrus. Structures of the isolated compounds were established by spectroscopic analysis, including UV, IR, HRESI-MS, and 1D/2D NMR. The total extract and some isolated compounds were determined against DPPH (2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazinyl radical, for their free radical scavenging activity, the total alcoholic extract showed strong antioxidant activity while the two new compounds showed weak antioxidant activity.     

Triterpene glycosides from red ginseng marc and their anti-inflammatory activities

Three new triterpene glycosides ursan-3β,19α,22β-triol-3-O-β-d-glucopyranosyl (2′→1″)-β-d-glucopyranoside (1), ursan-3α,11β-diol-3-O-α-d-glucopyranosyl-(6′→1″)-α-d-glucopyranosyl-(6″→1‴)-α-d-glucopyranosyl-(6‴→1‴′)-α-d-glucopyranoside (2) and lanost-5,24-dien-3β-ol-3-O-β-d-glucopyranosyl-(6′→1″)-β-d-glucopyranosyl-(6″→1‴)-β-d-glucopyranoside (3), together with one known compound were isolated and identified from the marc of red ginseng. Their structures were elucidated by spectroscopic data analysis. Compounds (1–3) were investigated for anti-inflammatory effects using the RAW 264.7 macrophage cell line. In the cell proliferation assay, lipopolysaccharide stimulation decreased cell proliferation of RAW 264.7 macrophage cells, but the suppression of cell proliferation was significantly protected by treatment with compounds 2 and 3. Compounds 2 and 3 had a suppressive effect on the production of nitric oxide (NO), and they inhibited mRNA expression of proinflammatory mediators such as inducible nitric oxide synthase, and cyclooxygenase-2, and proinflammatory cytokines such as two interleukins and tumor necrosis factor-α. These findings suggest that compounds 2 and 3 have potential anti-inflammatory activities.