Schisarisanlactones A and B: A new class of nortriterpenoids from the fruits of Schisandra arisanensis

Two novel highly oxygenated nortriterpenoids, schisarisanlactones A (1) and B (2), have been isolated from the fruits of Schisandra arisanensis, an endemic plant of Taiwan. Compounds 1 and 2 possess an unprecedented 5/5/7/5/5-fused pentacyclic ring system. The structures of both compounds were determined on the basis of spectroscopic analyses, especially 2D NMR and MS. A plausible biogenetic pathway of 1 was proposed. Schisarisanlactone A (1) showed significant anti-HIV activity.     

Ursolic acid analogues: non-phenolic functional food components in Jamaican raspberry fruits

The Rubus genus produces numerous species that are known for their medicinal properties. Rubus rosifolius, called the red raspberry, grows wild in elevated regions in Jamaica. Phytochemical examination of the ethyl acetate extract of the fruit yielded eight compounds of the 19-α-hydroxyursane type: euscaphic acid (1), 1-β-hydroxyeuscaphic acid (2), hyptatic acid B (3), 19α-hydroxyasiatic acid (4), trachelosperogenin (5), 4-epi-nigaichigoside F1 (6), nigaichigoside F1 (7), and trachelosperoside B-1 (8), as confirmed by NMR spectroscopy. Inhibition of cell proliferation by these compounds were determined by using MCF-7 (breast), SF-268 (CNS), NCI H460 (lung), HCT-116 (colon) and AGS (gastric) human tumour cells. Among the human tumour cell lines assayed, only compounds 3 and 6 displayed significant growth inhibition and was specific to colon tumour cells by 56% and 40%, respectively. These ursolic acid analogues were also tested for anti-inflammatory activity using in vitro cycloxegenase-1 (COX-1) and cycloxegenase-2 (COX-2) enzyme inhibitory assays. Compounds 1, 2 and 3 showed selective COX-1 enzyme inhibitory activity (13%, 25% and 35%) at 25 μg/ml. In the lipid peroxidation (LPO) inhibitory assays, compounds 2, 4, 7 and 6 inhibited LPO by 62%, 60%, 53% and 68%, respectively, at 25 μg/ml.     

Phenolic compounds isolated from Zingiber officinale roots inhibit cell adhesion

Inhibitors of cell adhesion molecule-mediated cell adhesion might be novel therapeutic agents for the treatment of various inflammatory diseases. In this study, nine phenolic compounds were isolated from the methanol extracts of Zingiber officinale roots by bioactivity-guided fractionation. The structures of the compounds were determined by spectroscopic analysis (¹H, ¹³C NMR and MS), to be 6-gingerol (1), 8-gingerol (2), 10-gingerol (3), 6-shogaol (4), 8-shogaol (5), 10-shogaol (6), dehydro-6-gingerdione (7), dehydro-10-gingerdione (8) and 6-paradol (9). Compounds 3, 4, 5 and 7 inhibited direct binding between sICAM-1 and LFA-1 of the THP-1 cells in a dose-dependent manner with IC₅₀ values of 57.6, 27.1, 65.4 and 62.0 μM, respectively. Compounds 4 and 7 had an inhibitory effect on direct binding between sVCAM-1 and VLA-4 of THP-1 cells. These results suggest that the phenolic compounds from Z. officinale roots are good candidates for therapeutic strategies aimed at inflammation.     

Norditerpenoids from Agathis macrophylla

Three new norditerpenoids, (4S,5R,9S,10R)-methyl 19-hydroxy-15,16-dinorlabda-8(17),11E-dien-13-oxo-18-oate (1), (4R,5R,9R,10R,13S/R)-13-hydroxypodocarp-8(14)-en-19-oic acid (2/3) were isolated from Agathis macrophylla, together with 11 known diterpenoids. The structures of these compounds, 1-14, were established, mainly by spectroscopic analysis. The inactivation of protein tyrosine phosphatase 1B (PTP1B) by compounds 5-9 and 11-13 was tested and the cytotoxicity of compounds 1-14 against HL60 cell and SMMC-7721 cell were evaluated. Biological screening studies indicated that compounds 5, 7/8 and 9 were mild inactivators of PTP1B, whilst compounds 1, 4, 6, 7/8, and 10-12 exhibited moderate activity against both of the tested cell lines.     

Biguaiascorzolides A and B: Two novel dimeric guaianolides with a rare skeleton,from Scorzonera austriaca

The root of Scorzonera austriaca has been used in indigenous cuisines as a delicious food and in the Tibetan traditional medicine in northwestern China. Two novel dimeric guaianolides linked by a carbon–carbon bond with a rare carbon skeleton, termed biguaiascorzolides A (1) and B (2), respectively, have been isolated from roots of S. austriaca. Acetylation of 1 gave 1a. The structures of 1, 1a and 2 were characterised by HR-ESI-MS, EI-MS, UV, IR, and 1D- and 2D-NMR techniques (¹H and ¹³C NMR, ¹H-¹H COSY, HMQC, HMBC, and NOESY experiments). The cytotoxicity of 1a was assayed against selected cancer cell lines, including the human erythroleukaemia adriamycin-resistant subline (K562/ADM) and human stomach carcinoma (MGC-803) cell lines. Compound 1a exhibits a moderate activity against K562/ADM cell lines (IC₅₀ 39.8 μm) and is inactive towards MGC-803 cell lines.     

Antioxidants of therapeutic relevance in COPD from the neotropical blueberry Anthopterus wardii

Four flavone C-glycosides, isoorientin (1), orientin (2), vitexin (3), and isovitexin (4), were isolated from the neotropical blueberry of Anthopterus wardii, a so-called “superfruit”, using antioxidant activity-guided fractionation. A dose-response relationship of compounds 1-4 was determined for their anti-inflammatory activity against interleukin-8 (IL-8) and for the inhibition of matrix metalloproteinase-1 (MMP-1) expression, an inflammatory marker for chronic obstructive pulmonary disease. The four flavone C-glycosides exhibited inhibitory activity against IL-8 production and MMP-1 expression, with compounds 1, 3, and 4 having the most potent inhibitory activities in both assays at 100 μg/ml. The structures of compounds 1-4 were determined by spectroscopic methods. These flavone C-glycosides are reported for the first time in the Anthopterus genus.     

Phenolic constituents from the flower buds of Lonicera japonica and their 5-lipoxygenase inhibitory activities

Thirteen phenolic constituents, luteolin (1), protocatechuic acid (2), caffeic acid (3), flavoyadorinin-B (4), 4,5-dicaffeoylquinic acid (5), luteolin 7-O-β-d-glucopyranoside (7), 3,5-dicaffeoylquinic acid methyl ester (8), methyl chlorogenate (9), quercetin 3-O-β-d-glucopyranoside (10), 3,5-dicaffeoylquinic acid (11), rhoifolin (12), chlorogenic acid (13), and a novel phenolic glucoside benzoate, vanillic acid 4-O-β-d-(6-O-benzoylglucopyranoside) (6), were isolated from the flower buds of Lonicera japonica. Flavoyadorinin-B (4) was isolated for the first time from a Caprifoliaceae plant. The structures of 1–13 were determined on the basis of chemical and spectroscopic evidence. These compounds were screened for their 5-lipoxygenase inhibitory activity. Only luteolin (1) showed significant inhibitory activity against 5-LOX-catalysed leukotriene production.     

A new benzoquinone and a new benzofuran from the edible mushroom Neolentinus lepideus and their inhibitory activity in NO production inhibition assay

The fruiting bodies or mycelia of mushrooms have been used as food and food-flavoring material for centuries due to their nutritional and medicinal value and the diversity of their bioactive components. The present research is the first to investigate the bioactive secondary metabolites from the solid culture of the edible mushroom Neolentinus lepideus. Two new secondary metabolites, 5-methoxyisobenzofuran-4,7(1H,3H)-dione (1) and 1,3-dihydroisobenzofuran-4,6-diol (2), as well as seven known compounds including one benzoquinone derivative (3) and six cinnamic acid derivatives (4–9) were obtained. Their structures were established by means of spectroscopic methods, including 1D and 2D NMR. The bioactivity on the nitric oxide production in lipopolysaccharide-induced macrophages was evaluated for all metabolites (1–9) isolated. Compound 1 showed strong NO inhibitory activity with the IC₅₀ value of 6.2 μM. Compound 2 displayed moderate NO inhibitory activity with the IC₅₀ value of 88.8 μM. In the DPPH scavenging assay, compound 2 displayed antioxidant activity with IC₅₀ of 68.6 μM. The discovery of new NO production inhibitors from N. lepideus expands its usage as a functional food.     

Effects of Amelanchier fruit isolates on cyclooxygenase enzymes and lipid peroxidation

Bioassay-directed isolation and purification of the ethyl acetate and methanol extracts of Amelanchier canadensis resulted in 1,3-dilinoleoyl 2-olein (1), 1,3-dioleoyl 2-linolein (2), 5-hydroxymethyl-2-furfural (3), 5-(sorbitoloxymethyl)-furan-2-carboxaldehyde (4), 5-(mannitoloxymethyl)-furan-2-carboxaldehyde (5), and 5-(α-d-glucopyranosyloxymethyl) furan-2-carboxaldehyde (6). Four compounds, oleanolic acid (7), ursolic acid (8), kaempferol-3-O-α-l-rhamnopyranosyl (1 ← 2) rhamnopyranoside (9), and kaempferol-3-O-α-l-rhamnopyranoside (10) were isolated from the ethyl acetate extract of fresh fruits of Amelanchier arborea. The compounds were isolated and purified by various chromatographic techniques and characterized by NMR and GC/MS methods. The isolated compounds inhibited lipid peroxidation (by 85%) at 100 ppm when compared to 89%, 87%, and 98% for the commercial antioxidants butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), and tert-butylhydroxyquinone (TBHQ) at 1.67, 2.2, and 1.67 ppm, respectively. Although not selective, some of these compounds inhibited cyclooxygenase (COX)-1 and -2 enzymes. Compounds 3–6 were isolated for the first time from A. canadensis and compounds 7–10 were isolated for the first time from A. arborea fruits.     

Sesquiterpenes from the rhizome of Curcuma longa with inhibitory activity on superoxide generation and elastase release by neutrophils

Six new sesquiterpenes, curculonone A (1), curculonone B (2), curculonone C (3), curculonone D (4), 6α-hydroxycurcumanolide A (5), and 1,10-dehydro-10-deoxy-9-oxozedoarondiol (6), have been isolated from the rhizome of Curcuma longa, together with 19 known compounds. The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 2, 5, 12, 15, 16, and 23 exhibited inhibition (IC₅₀ ? 18.22 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 5, 12–16, and 23 inhibited fMLP/CB-induced elastase release with IC₅₀ values ? 14.28 μM.     

Glycosidase inhibitory phenolic compounds from the seed of Psoralea corylifolia

The seeds of Psoralea corylifolia were extracted into five different polar solvents: chloroform, 50% ethanol in water, ethanol, methanol and water. All extracts were evaluated for glycosidase inhibitory activity. The chloroform extract (CE) showed the lowest IC₅₀ values against α-glucosidase (82.9 μg/ml) and α-mannosidase (132 μg/ml). Chromatography of CE yielded nine phenolic compounds which were identified as isovabachalcone (1), 4′-O-methylbavachalcone (2), isobavachromene (3), corylifolin (4), bavachinin (5), psoralidin (6), neobavaisoflavone (7), corylifol A (8), and bakuchiol (9). All isolated compounds, apart from compound 5, possessed α-glucosidase inhibitory activities. Among them, compounds 6–8 exhibited potent inhibition with IC₅₀s of 13.7, 27.7 and 11.3 μM, respectively. Furthermore, compounds 2 and 6 showed α-mannosidase inhibitory activity. Mechanistic analysis of their inhibition modes against α-glucosidase showed that compounds (6 and 7) were noncompetitive, whereas compound 8 was mixed. Furthermore, the most active glycosidase inhibitors (2, 6–8) were proven to be present in the native seed in high quantities by an HPLC chromatogram.     

New alkaloids from Capparis spinosa: Structure and X-ray crystallographic analysis

Fruits of Capparis spinosa contain a significant amount of compounds with many health benefits. Three new alkaloids, capparisine A (1), capparisine B (2), capparisine C (3), and two known alkaloids, 2-(5-hydroxymethyl-2-formylpyrrol-1-yl) propionic acid lactone (4), and N-(3′-maleimidy1)-5-hydroxymethyl-2-pyrrole formaldehyde (5) were isolated from the fruits of C. spinosa L. The five compounds were purified by solvent separation, column chromatography, and preparative HPLC, consecutively. The chemical structures of compounds 1–5 were established on the basis of a spectroscopic analysis, and the stereochemistries of compounds 1 and 2 were proved by X-ray crystallographic analysis. Nevertheless, the five compounds had no inhibitory effect on the human hepatocyte cell line HL-7702 apoptosis induced by Act D (200 ng/ml) and TNF-α (20 ng/ml) with high content screening assay.     

Protective effects of triterpenoids from Ganoderma resinaceum on H2O2-induced toxicity in HepG2 cells

Ganoderma resinaceum Boud. (Polyporeseae) has long been used for antioxidant, immunoregulation and liver protection. From the fruiting bodies of G. resinaceum, eight new lanostanoids, lucidones D–G (1–4), 7-oxo-ganoderic acid Z₂ (5), 7-oxo-ganoderic acid Z₃ (6), ganoderesin A (7), and ganoderesin B (8), together with six known lanostanoids (9–14) were isolated. The structures of new compounds were elucidated through extensive spectroscopic analysis. In an in vitro model, ganoderesin B (8), ganoderol B (10) and lucidone A (11) showed inhibitory effects against the increase of ALT and AST levels in HepG2 cells induced by H₂O₂ compared to a control group in the range of their maximum non-toxic concentration (MNTC). However, compounds 8, 10 and 11 displayed no anti-oxidant activities by DPPH assay. Meanwhile, activation for PXR (Pregnane X Receptor) of ganoderesin B (8), ganoderol B (10) and lucidone A (11) was evaluated; ganoderol (10) exhibited a vital activation for PXR-induced CYP3A4 expression. These results suggested that GTs (Ganoderma triterpenoids) exhibited hepatoprotective activities by lowering ALT and AST levels.     

Immunoprecipitation coupled with HPLC–MS/MS to discover the aromatase ligands from Glycyrrhiza uralensis

Affinity chromatography, applied to discover the enzyme inhibitors, needs special column with target protein and its carrier. Selection of stationary phase and mobile phase needs careful considerations due to the characteristics of proteins. In this study, a method immunoprecipitation (IP) coupled with HPLC-DAD–MS was developed to discover the aromatase ligands from Glycyrrhiza uralensis. An SB-C18 column was employed to separate target compounds without special consideration in mobile phase. Twenty-one compounds, including isolated compounds 4, 7, 8, 10, 11, 13, 15, 18–20, 23 and non-isolated compounds A-J, were found to have good affinity to aromatase by LC–MS. Seven of them (7, 15, 18, 19, 23, D, E) were detected to bind with aromatase in MCF-7 cells by IP coupled with HPLC–MS/MS. Bioassays disclosed aromatase inhibitory activities of the isolated compounds mentioned above, verifying the efficiency of IP coupled with HPLC–MS/MS as a method to screen aromatase ligands.     

Spirostane,furostane and cholestane saponins from Persian leek with antifungal activity

A phytochemical investigation of the seeds of Persian leek afforded the isolation of two new spirostane glycosides, persicosides A (1) and B (2), four new furostane glycosides, isolated as a couple of inseparable mixture, persicosides C1/C2 (3a/3b) and D1/D2 (4a/4b), one cholestane glycoside, persicoside E (5), together with the furostane glycosides ceposides A1/A2 and C1/C2 (6a/6b and 7a/7b), tropeosides A1/A2 and B1/B2 (8a/8b and 9a/9b), and ascalonicoside A1/A2 (10a/10b), already described in white onion, red Tropea onion, and shallot, respectively. Structure elucidation of the compounds was carried out by comprehensive spectroscopic analyses, including 2D NMR spectroscopy and MS spectrometry, and by chemical evidences. The chemical structure of new compounds were identified as (25S)-spirostan-2α,3β,6β-triol 3-O-[β-d-glucopyranosyl-(1 → 3)] [β-d-xylopyranosyl-(1 → 2)]-β-d-glucopyranosyl-(1 → 4)-β-d-galactopyranoside (1), (25S)-spirostan-2α,3β,6β-triol 3-O-[β-d-xylopyranosyl-(1 → 3)] [α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranosyl-(1 → 4)-O-β-d-galactopyranoside (2), furosta-1β,3β,22ξ,26-tetraol 5-en 1-O-β-d-glucopyranosyl (1 → 3)-β-d-glucopyranosyl (1 → 2)-β-d-galactopyranosyl 26-O-α-l-rhamnopyranosyl (1 → 2)-β-d-galactopyranoside (3a,3b), furosta-2α,3β,22ξ,26-tetraol 3-O-β-d-glucopyranosyl (1 → 3)-β-d-glucopyranosyl (1 → 2)-β-d-galactopyranosyl 26-O-β-d-glucopyranoside (4a,4b), (22S)-cholesta-1β,3β,16β,22β-tetraol 5-en 1-O-α-l-rhamnopyranosyl 16-O-α-l-rhamnopyranosyl (1 → 2)-β-d-galactopyranoside (5).     

Novel acetylated flavonoid glycosides from the leaves of Allium ursinum

Seven flavonoid glycosides, kaempferol 3-O-α-L-rhamnopyranosyl (1→2)-[3-O-acetyl]-β-D-glucopyranoside (1), kaempferol 3-O-α-L-rhamnopyronosyl (1→2)-[6-O-acetyl]-β-D-glucopyranoside (2), kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (3), kaempferol 3-O-β-D-glucopyranoside (4), kaempferol 3,7-di-O-β-D-glucopyranoside (5), 7-O-β-D-glucopyranosyl kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (6), kaempferol 3-O-α-L-rhamnopyranosyl (1→2)-β-D-glucopyranoside-7-O-[2-O-(trans-p-coumaroyl)]-β-D-glucopyranoside (7) were isolated from the n-butanol fraction of Allium ursinum L. and the structures of these compounds were elucidated on the basis of mass spectrometry, ¹H NMR, ¹³C NMR, HMQC and HMBC data. Among them, 1 and 2 are novel compounds and compounds 4 and 5 were isolated from this plant species for the first time.     

Terpenoids from Stinking toe (Hymneae courbaril) fruits with cyclooxygenase and lipid peroxidation inhibitory activities

Stinking toe (Hymenaea courbaril), also called Jatoba and Kerosene tree, is a medicinal plant commonly found in the central and South American countries. In the Caribbean, Mexico and Brazil, the powdery sweet dust of its fruit is consumed for energy. The chemical examination of the yellowish sweet powder of the fruit yielded sucrose and linolenic acid as major compounds. The pods yielded the labdane diterpenoids crotomachlin (1), labd-13E-en-8-ol-15-oic acid (2), labdanolic acid (4), (13E)-labda 7, 13 dien-15-oic acid (5) and labd-8 (17), 13E- dien-15-oic acid (6), along with the sesquiterpene, spathulenol (7), as confirmed by ¹H and ¹³C NMR spectral studies. The methyl ester of labd-13E-en-8-ol-15-oic acid (3) was also characterized during the purification of compound 5. The total amount of these terpenoids in the fruit was about 0.1% (w/w) of the dried fruit. Compounds 1–5 and 7 were assayed for anti-inflammatory activity using cyclooxygenase-1 (COX-1) and -2 (COX-2) enzymes. At 100 ppm, compounds 3 and 4 showed selective COX-2 enzyme inhibition. Also, compounds 1, 2 and 5 inhibited lipid peroxidation by 46%, 48% and 75%, respectively, at 100 ppm. These compounds were isolated from this fruit and their COX and lipid peroxidation inhibitory activities are reported for the first time in this paper.     

Dicaffeoylquinic acid derivatives and flavonoid glucosides from glasswort (Salicornia herbacea L.) and their antioxidative activity

Two novel antioxidant compounds, isoquercitrin 6″-O-methyloxalate (6) and methyl 4-caffeoyl-3-dihydrocaffeoyl quinate (salicornate, 7), were isolated from Salicornia herbacea L.. Six known compounds were also identified as 3,5-dicaffeoylquinic acid (1), quercetin 3-O-β-d-glucopyranoside (2), 3-caffeoyl-4-dihydrocaffeoylquinic acid (3), methyl 3,5-dicaffeoyl quinate (4), 3,4-dicaffeoylquinic acid (5), and isorhamnetin 3-O-β-d-glucopyranoside (8). Their chemical structures were determined by spectroscopic data from ESI–MS and NMR. The isolated dicaffeoylquinic acid derivatives (1, 3, 4, 5, and 7) showed similar activities for scavenging 1,1-diphenyl-2-picrylhydrazyl radicals and inhibiting formation of cholesteryl ester hydroperoxide during copper ion-induced rat blood plasma oxidation. The two flavonol glucosides (2 and 6), which have no substitutions in the B ring of their aglycones, also had similar activity. However, compound 8, which has the same structure as 2 except for the presence of a methoxyl group in the C-3′ position of the B ring, showed predominantly lower antioxidant activity than the other isolated compounds.     

Isolation,characterization, and neuroprotective activities of sesquiterpenes from Petasites japonicus

Neuroprotective reagents to protect the nerve cells against oxidative stress and other damages are potentially effective for the medical treatment of Parkinson’s disease. Petasites japonicus, a wild vegetable, belongs to the family Compositae and its extract has shown the neuroprotective effects. A further phytochemical investigation of P. japonicus for neuroprotective substances led to the isolation of eight new (1–8) and two known (9 and 10) sesquiterpenes. Their structures were elucidated on the basis of extensive 1D and 2D NMR (HMQC, HMBC, ¹H–¹H COSY, and NOESY) spectroscopic data analyses, and the structure of 1 was confirmed by X-ray crystallography. The neuroprotective activities of these sesquiterpenes were evaluated against cobalt chloride (CoCl₂)-induced neuronal cell death in human dopaminergic SH-SY5Y cells. Five compounds showed a neuroprotective activity.