Potential α-glucosidase inhibitors from thermal transformation of (+)-catechin

Thermal transformation of the (+)-catechin (1) with heating processing afforded a new oxidation product, gambiriin D (2), along with catechin [6′–8]-catechin (3), and (+)-epicatechin (4). The structure of a new catechin dimer with C–C linkage was determined on the basis of spectroscopic data interpretation. The catechin dimers 2 and 3 exhibited significantly improved inhibitory activities against α-glucosidase, with IC₅₀ values of 0.16 ± 0.2 and 0.14 ± 0.2 μM, respectively, when compared to parent (+)-catechin. Kinetic analysis showed that the two effective compounds 2 and 3 have noncompetitive modes of action.     

Chemical constituents from Oncocalyx glabratus and their biological activities

Chemical investigation of the aerial parts of Oncocalyx glabratus resulted in the isolation of three new flavan derivatives, 5,3′,4′-trihydroxyflavan 7-O-gallate (1), 5,4′-dihydroxyflavan 7-3′-O-digallate (2) and 5,3′-dihydroxyflavan 7-4′-O-digallate (3), named oncoglabrinol A, B and C, respectively, together with four known flavonols, (+)-catechin (4), (+)-catechin-7-O-gallate (5), catechin-7-4′-O-digallate (6A) and catechin-7-3′-O-digallate (6B). The structures of the compounds were established by 1D, 2D NMR and ESI-HRMS spectral analyses. The biological activity of the compounds was tested through a series of in vitro assays designed for determining cytotoxicity, antiviral activity against hepatitis B virus, and antidiabetic activity. All compounds were found non-toxic and showed moderate anti-HBV activity. Compounds 3 and 6 showed dual PPAR agonistic activity while others were not effective.     

Chemical constituents from the stems of Tripterygium regelii

Phytochemical investigation on the stems of Tripterygium regelii resulted in the isolation of fourteen compounds, including six flavonoids (1–6), seven lignans (7–13), and one cyanogenic glycoside (14). This is the first report of the four dimeric flavonoids bis-8, 8′-catechinylmethane (2), bis (8-epicatechinyl) methane (3), bis-6, 8′-catechinylmethane (4) and montahomobisflavan B (5) from a species of Tripterygium. Previously, these dimeric flavonoids have been mainly identified from species of gymnosperms. This research has shown that the main secondary metabolisms identified in T. regelii were flavonoids and lignans. These data enable this species to be differentiated from T. wilfordii and T. hypoglaucum that contain the triptolide-resembling diterpenoids.     

Phenolic constituents from the roots of Rosa laevigata (Rosaceae)

Chemical investigation of the root of Rosa laevigata led to the isolation of sixteen phenolic compounds, including seven flavonoids (1–7), five condensed tannins (8–12), two stilbenes (13 and 14) and two benzoic acid derivatives (15 and 16). Their structures were identified as (+)-catechin (1), (+)-gallocatechin (2), (2R, 3S, 4S)-cis- leucocyanidin (3), (2R, 3S, 4S)-cis-leucofisetinidin (4), (2S, 3R, 4R)-cis- leucofisetinidin (5), dehydrodicatechin A (6), phloridzin (7), procyanidin B3 (8), fisetinidol-(4α, 8)-catechin (9), guibourtinidol- (4α, 8)-catechin (10), ent- isetinidol -(4α, 6)-catechin (11), fisetinidol-(4β, 8)-catechin (12), (Z)-3-methoxy-5-hydroxy- stilbene (13), (Z)-piceid (14), gallic acid (15) and 4-hydroxybenzoic acid- 4-O-β-D-glucopyranoside (16). Among them, compounds 3–7, 9–14, and 16 were isolated from R. laevigata for the first time, and compounds 3–7, 9, 10, 12–14 and 16 were reported for the first time from the genus Rosa. The chemotaxonomic significance of these compounds was summarized.     

Pyranocoumarins from Glehnia littoralis inhibit the LPS-induced NO production in macrophage RAW 264.7 cells

A new dihydropyranocoumarin, (+)-cis-(3′S,4′S)-diisobutyrylkhellactone (1), together with five known compounds, 3′-senecioyl-4′-acetylkhellactone (2), 3′-isovaleryl-4′-acetylkhellactone (3), 3′,4′-disenecioylkhellactone (4), 3′-isovaleryl-4′-senecioylkhellactone (5), and 3′,4′-diisovalerylkhellactone (6), was isolated from Glehnia littoralis. Their chemical structures were elucidated based on the spectroscopic data interpretation, particularly 1D and 2D NMR data including HMQC and HMBC. All the isolated compounds showed the potential to inhibit LPS-induced nitric oxide production in RAW 264.7 cells with IC₅₀ values ranging from 7.4 to 44.3 μM.     

Chemotaxonomic significance of lignans from Serissa japonica (Thunb.) Thunb

Sixteen known lignans were isolated from the 95% alcohol extract of the whole plant of Serissa japonica (Thunb.) Thunb., including nine furofurans (1–9), three tetrahydrofurans (10–12) and four arylnaphthalenes (13–16). In the present report, compounds (+)-epipinoresinol (1), (+)-1-hydroxy-6-epipinoresinol 4,4″-di-O-methyl ether (3), (−)-pinoresinol (4), (+)-8-hydroxypinoresinol (6), pseuderesinol (7), (+)-1-hydroxysyringaresinol (8), (−)-(7′S,8S,8′R)-4,4′-dihydroxy-3,3′,5,5′-tetramethoxy-7′,9-epoxylignan-9′-ol-7-one (10), wikstrone (11), 7'-(+)-oxomatairesinol (12), (+)-cycloolivil (13), (+)-isolariciresinol (14), 5-methoxy-(+)-isolariciresinol (15) and cyclolignans (16) were reported from the Serissa genus for the first time, and compounds (+)-lirioresinol A (2) and (−)-lirioresinol B (5) were firstly isolated from the plant. Their structures were elucidated on the basis of extensive spectroscopic and chemical analyses. Moreover, the chemotaxonomic significance of the isolated compounds is discussed.     

A furan-2-carbonyl C-glucoside and an alkyl glucoside from the parasitic plant,Dendrophthoe pentandra

A new furan-2-carbonyl C-(6′-O-galloyl)-β-glucopyranoside (scleropentaside F, 1) and a new alkyl glucoside [butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside, 2] were isolated from the entire hemi-parasitic plant, Dendrophthoe pentandra growing on Tectona grandis together with ten known compounds including, benzyl-O-β-d-glucopyranoside (3), benzyl-O-α-l-rhamnopyranosyl-(1 → 6)-β-d-glucopyranoside (4), benzyl-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranoside (5), methyl gallate 3-O-β-d-glucopyranoside (6), methyl gallate 3-O-(6′-O-galloyl)-β-d-glucopyranoside (7), (+)-catechin (8), procyanidin B-1 (9) and procyanidin B-3 (10), bridelionoside A (11), and kiwiionoside (12). In addition, compounds 1, 3–9 were isolated from this species growing on the different host, Mangifera indica. The structure elucidations were based on physical data and spectroscopic evidence including 1D and 2D experiments.     

Biflavonoids from the bark roots of Poincianella pyramidalis (Fabaceae)

Poincianella pyramidalis (Fabaceae) is an endemic tree that grows in semiarid regions of Brazil. Phytochemical investigations on the bark roots of this plant led to the isolation of four new biflavonoids named (+)-5-hydroxy-7,4′-dimethoxyflavone-3α-2′′′-hydroxy-4′′′,4′′-dimethoxydihydrochalcone (1), (+)-5,7-dihydroxy-4′-methoxyflavone-3α-2′′′-hydroxy-4′′′,4′′-dimethoxydihydrochalcone (2), (−)-7-hydroxy-4′-methoxyflavone-3α-2′′′,4′′′-dihydroxy-4′′-methoxydihydrochalcone (3), (−)-7,4′-dihydroxy-flavanone-3,8-5′′,6′′,4′′-trihydroxy-flavone (4), and the previously identified compound 4,2′,4′,4′′,2′′′,4′′′-hexahydroxy-3,5′′′-bichalcone (rhuschalcone VI, 5). Their structures were determined by HR-ESI-MS and extensive analyses of NMR spectroscopic data.     

Tetraoxygenated xanthones and biflavanoids from the twigs of Garcinia merguensis

One new tetraoxygenated xanthone, merguensinone (1), along with one known xanthone, 1,5,6-trihydroxy-2-prenyl-6′,6′-dimethyl-2H-pyrano(2′,3′:3,4)xanthone (2) and five known biflavanoids, (?)-GB-1a (3), (?)-GB-2a (4), (+)-morelloflavone (5), (+)-volkensiflavone (6), and amentoflavone (7) were isolated from the methanol extract from the twigs of Garcinia merguensis. Their antibacterial activity against the standard Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus and antioxidation activity with DPPH assay were examined.     

Phytochemical and chemotaxonomic study on Piper pleiocarpum Chang ex Tseng

The phytochemical study of Piper pleiocarpum Chang ex Tseng led to the isolation of eighteen compounds (1–18), including ten lignanoids, galbelgin (1), (+) sesamin (2), denudatin A (3), hancinone (4), (7S,8S, 3′R)-Δ^8'-3,3′,4-trimethoxy-3′,6′-dihydro-6′-oxo-7.0.4′,8.3′-lignan[(2S,3S,3aR)-2-(3,4-dimethoxyphenyl)-3,3a-dihydro-3a-methoxy-3-methyl-5-(2-propenyl)-6(2H))-benzofuranone] (5), (−)-(7R,8R)-machilin D (6), (1R,2R)-2-[2-methoxy-4-((E)-prop-1-enyl)phenoxy]-1-(3,4-dimethoxyphenyl)propyl acetate (7), piperbonin A (8), machilin D (9), 4-methoxymachilin D (10), one amide alkaloid, Δ^α,β-dihydropiperine (11), six polyoxygenated cyclohexenes, ent-curcuminol F (12), uvaribonol E (13), ellipeiopsol A (14), 1S,2R,3R,4S-1-ethoxy-2-[(benzoyloxy)methyl]cyclohex-5-ene-2,3,4-triol, 3-acetate (15), (+)-crotepoxide (16), (+)-senediol (17), and one benzoate derivative, 2-acetoxybenzyl benzoate (18). Their structures were established by spectroscopic data and by comparison with the literature. All the compounds were firstly isolated from P. pleiocarpum, while ten compounds 6–7, 9–10, 12–15, 17–18 were isolated from the genus Piper and the family Piperaceae for the first time. The chemotaxonomic significance of these compounds was also discussed. The isolation of compounds 6–7, 9–10 may be used as chemotaxonomic markers for the genus of Piper.     

New ellagitannin and galloyl esters of phenolic glycosides from sapwood of Quercus mongolica var. crispula (Japanese oak)

Two novel glycosides, 4,5-dimethoxy-3-hydroxyphenol 1-O-β-(6′-O-galloyl)-glucopyranoside (1) and (+)-2α-O-galloyl lyoniresinol 3α-O-β-d-xylopyranoside (2), as well as a novel ellagitannin named epiquisqualin B (3), were isolated from sapwood of Quercus mongolica var. crispula along with 19 known phenolic compounds. The structures of the novel compounds were elucidated on the basis of chemical and spectroscopic investigation. Compound 2 is the first example of a lignan galloyl ester, and 3 is the oxidation product of vescalagin, which is the major ellagitannin of this plant.     

Synthesis and antioxidant activity of a procyanidin B3 analogue

Proanthocyanidin, an oligomer of catechin, is a natural antioxidant and a potent inhibitor of lectin-like oxidized LDL receptor-1, which is involved in the pathogenesis of arteriosclerosis. We synthesized proanthocyanidin analogue 1, in which the geometry of one catechin molecule in procyanidin B3, a dimer of (+)-catechin, is constrained to be planar. The antioxidant activities of the compounds were evaluated in terms of their capacities to scavenge galvinoxyl radicals, and results demonstrate that while procyanidin was 3.8 times more potent than (+)-catechin, the radical scavenging activity of proanthocyanidin analogue 1 was further increased to 1.9 times that of procyanidin B3. This newly designed proanthocyanidin analogue 1 may be a promising lead compound for the treatment of arteriosclerosis and related cerebrovascular diseases.     

Two new glycosides and one new neolignan from the roots of Cynanchum stauntonii

Three new compounds including one C₂₁-steroidal glycoside, one methylglycoside, and one neolignan, named as Deoxyamplexicogenin A-3-O-yl-4-O-(4-O-α-l-cymaropyranosoyl-β-d-digitoxopyranosoyl)-β-d-canaropyranoside (1), Methyl-O-α-l-cymaropyranosoyl-(1 → 4)-β-D-digitoxopyranoside (2), and (+)-(7S, 8R, 7′E)-5-hydroxy-3, 5′-dimethoxy-4′, 7-epoxy-8, 3′-neolign-7′-ene-9, 9′-diol 9′-ethyl ether (3), respectively, were isolated from the roots of Cynanchum stauntonii. The structure elucidations were achieved by in-depth spectroscopic examination, mainly including the experiments and analyses of multiple 1D- and 2D-NMR and HRESIMS and CD analysis and qualitative chemical tests. Cytotoxicity activities of compounds 1–3 were evaluated against five tumor cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) in cell based assays where they were found to be inactive.     

Alkenylresorcinols and cytotoxic activity of the constituents isolated from Labisia pumila

Phytochemical investigation on the leaves of Labisia pumila (Myrsinaceae), an important medicinal herb in Malaysia, has led to the isolation of 1-O-methyl-6-acetoxy-5-(pentadec-10Z-enyl)resorcinol (1), labisiaquinone A (2) and labisiaquinone B (3). Along with these, 16 known compounds including 1-O-methyl-6-acetoxy-5-pentadecylresorcinol (4), 5-(pentadec-10Z-enyl)resorcinol (5), 5-(pentadecyl)resorcinol (6), (−)-loliolide (7), stigmasterol (8), 4-hydroxyphenylethylamine (9), 3,4,5-trihydroxybenzoic acid (10), 3,4-dihydroxybenzoic acid (11), (+)-catechin (12), (−)-epicatechin (13), kaempferol-3-O-α-rhamnopyranosyl-7-O-β-glycopyranoside (14), kaempferol-4′-O-β-glycopyranoside (15), quercetin-3-O-α-rhamnopyranoside (16), kaempferol-3-O-α-rhamnopyranoside (17), (9Z,12Z)-octadeca-9,12-dienoic acid (18) and stigmasterol-3-O-β-glycopyranoside (19) were also isolated. The structures of these compounds were established on the basis of 1D and 2D NMR spectroscopy techniques (¹H, ¹³C, COSY, HSQC, NOESY and HMBC experiments), mass spectrometry and chemical derivatization. Among the constituents tested 1 and 4 exhibited strongest cytotoxic activity against the PC3, HCT116 and MCF-7 cell lines (IC₅₀ values ⩽10 μM), and they showed selectivity towards the first two-cell lines relative to the last one.     

Phytochemical and chemotaxonomic study on Ziziphus Jujuba Mill. (Rhamnaceae)

Fourteen compounds were isolated from fruits of Ziziphus jujuba Mill., including two flavonoids (1–2), one phenolic glycosides (3), one lignan (4), four phenols (5–8), three alkaloid (9–10, 14), three sesquiterpenoid (11–13). The structures of all the compounds were established by the NMR techniques, as well as by comparison with previously reported data in literature. Compounds 2″-glucosyl-8-C-glucosyl-4′-O-methylapigenin (1), 3′, 4′, 5′-trimethoxycinnamyl alcohol (5), 2-{4-[(1E)-3-Hydroxyprop-1-en-1-yl]-2, 6-dimethoxy-phenoxy}propane-1, 3-diol (6), 1-(4-Hydroxyphenyl)ethane-1, 2-diol (8), (1S, 3S)-1-Methyl-l, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (9), (1R, 3S)-1-Methyl-l, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid (10), grasshopper ketone (12), methyl (3R, 5R)-5-methoxy-3-phenylisoxazolidine-5-carboxylate (14) were firstly reported from the genus Ziziphus and the family Rhamnaceae. Furthermore, the chemotaxonomic significance of the isolates was discussed.     

Neolignans from Aniba lancifolia

The branches of the shrub Aniba lancifolia Kubitzki et Rodrigues (Lauraceae) contain besides 2-hydroxy-4,5- dimethoxyallylbenzene and its dimer cyclohexan-2-allyl- 5-en-4,5-dimethoxy-4-O-(2′-allyl-4′,5′-dimethoxyphenyl)-1-one (lancilin, 2) 6 further novel neolignans: (4S,2′R)- and (4R,2′E)-cyclohexan-2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-guaiacyl)-propyl]-1-one (lancifolins A and B, 3a and 3b), (4S,2′R)- and (4R,2′R)-cyclohexan- 2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-veratryl)-propyl]-1-one (lancifolins C and D, 3c and 3d), (4S,2′R)-and (4R,2′R)-cyclohexan-2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-piperonyl)-propyl]-1-one (lancifolins E and F, 3e and 3f).     

Neural cell protective compounds isolated from Phoenix hanceana var. formosana

A platform for screening drugs for their ability to protect neuronal cells against cytotoxicity was developed. Nerve growth factor (NGF) differentiates PC12 cells into nerves, and these differentiated PC12 cells enter apoptosis when challenged with 6-hydroxydopamine (6-OHDA). A screening spectrophotometer was used to assay cytotoxicity in these cells; pretreatment with test samples allowed identification of compounds that protected against this neuronal cytotoxicity. The 95% ethanol extract of Phoenix hanceana Naudin var. formosana Beccari. (PH) showed potential neuroprotective activity in these assays. The PH ethanol extract was further fractionated by sequential partitioning with n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and water. Subsequent rounds of assaying resulted in the isolation of ten constituents, and their structures were characterized by various spectroscopic techniques and identified by comparison with previous data as: isoorientin (1), isovitexin (2), veronicastroside (3), luteolin-7-O-β-d-glucopyranoside (4), isoquercitrin (5), tricin-7-neohesperidoside (6), tricin-7-O-β-d-gluco-pyranoside (7), (+)-catechin (8), (−)-epicatechin (9), and orientin 7-O-β-d-glucopyranoside (10). Among these compounds, isovitexin (2), luteolin-7-O-β-d-glucopyranoside (4) and (+)-catechin (8) showed significant neuroprotective activity in cell viability (WST-8 reduction), anti-apoptosis (Annexin V-FITC/propidium iodide double-labeled flow cytometry), and cellular ROS scavenging assays (besides isovitexin (2)), as well as a decreased caspase-8 activity in 6-OHDA-induced PC12 cells. Hence, isovitexin (2), luteolin-7-O-β-d-glucopyranoside (4), and (+)-catechin (8) protected PC12 cells from 6-OHDA-induced apoptotic neurotoxicity.     

Minor phenolics from Angelica keiskei and their proliferative effects on Hep3B cells

A new coumarin, (?)-cis-(3′R,4′R)-4′-O-angeloylkhellactone-3′-O-β-d-glucopyranoside (1) and two new chalcones, 3′-[(2E)-5-carboxy-3-methyl-2-pentenyl]-4,2′,4′-trihydroxychalcone (4) and (±)-4,2′,4′-trihydroxy-3′-{2-hydroxy-2-[tetrahydro-2-methyl-5-(1-methylethenyl)-2-furanyl]ethyl}chalcone (5) were isolated from the aerial parts of Angelica keiskei (Umbelliferae), together with six known compounds: (R)-O-isobutyroyllomatin (2), 3′-O-methylvaginol (3), (?)-jejuchalcone F (6), isoliquiritigenin (7), davidigenin (8), and (±)-liquiritigenin (9). The structures of the new compounds were determined by interpretation of their spectroscopic data including 1D and 2D NMR data. All known compounds (2, 3, and 6–9) were isolated as constituents of A. keiskei for the first time. To identify novel hepatocyte proliferation inducer for liver regeneration, 1–9 were evaluated for their cell proliferative effects using a Hep3B human hepatoma cell line. All isolates exhibited cell proliferative effects compared to untreated control (DMSO). Cytoprotective effects against oxidative stress induced by glucose oxidase were also examined on Hep3B cells and mouse fibroblast NIH3T3 cells and all compounds showed significant dose-dependent protection against oxidative stress.     

Flavan-3-ols from the leaves of Malaysian Uncaria longiflora var. pteropoda (Miq.) Ridsd

A novel flavonoid, (?)-2R,3R-3,5,4′-trihydoxyflavan-[6,7:5″,6″]-2″-pyranone, named uncariechin (1), was isolated from the methanolic extract of the leaves of Uncaria longiflora var. pteropoda (Miq.) Ridsd. along with the known (?)-epiafzelechin (2) and (?)-epicatechin (3), methyl 4-hydroxybenzoate and 4-hydroxybenzaldehyde, four pentacyclic oxindole alkaloids, isopteropodine, pteropodine, uncarine F and isopteropodic acid, previously found in the stems, and two coumarins, scopoletin and 3,4-dihydroxy-7-methoxycoumarin. Structures of the compounds were elucidated by 1D and 2D NMR, FTIR, UV, MS, and experimental as well as calculated electronic circular dichroism (ECD) data. Compounds 2 and 3 were evaluated for their neurotoxic and neuroprotective properties against differentiated SH-SY5Y neuroblastoma cell lines using the MTS assay. Compounds 2 and 3 did not show any neurotoxic effects but showed strong protective potential against hydrogen peroxide-induced neurotoxicity with maximum cell viability at a concentration of 1 μM.     

Insulin mimetic lanostane triterpenes from the cultivated mushroom Ganoderma orbiforme

Two new lanostane triterpenes, ganorbifoins A and B (1-2), together with the known compound (25S,3′S)-(+)-12α-hydroxy-3α-(3′-hydroxy-4′-methoxycarbonyl-3′-methylbutiryloxy)-24-methyllanosta-824-(31)-dien-26-oic acid (3) were isolated from the cultivated fruiting bodies of Ganoderma orbiforme. The structures of isolates were determined by extensive analysis of NMR and HRESIMS. All compounds induced glucose uptake in zebrafish-based system at the concentration of 10 μM. And the best performing compound is ganorbifoin A. Compounds 2 and 3 exhibited an inhibitory effect on nitric oxide production in LPS-induced BV-2 microglia cells at the concentration of 20 μM.