[A new benzopyran glycoside from Gentiana macrophylla].

Thirteen compounds were isolated and identified from 70% ethanol extract of the roots of Gentiana macrophylla by multi-chromatographic methods, including microporous resin, silica gel, and C_(18) reversed-phase column chromatography, as well as HPLC as follows: macrophylloside G(1), macrophylloside D(2), 5-formyl-2,3-dihydroisocoumarin(3),(+)-medicarpin(4),(+)-syringaresinol(5), liquiritigenin(6),(3R)-sativanone(7),(3R)-3'-O-methylviolanone(8), 4,2',4'-trihydroxychalcone(9), latifolin(10), gentioxepine(11), 6α-hydroxycyclonerolidol(12), and ethyl linoleate(13). Compound 1 was a new benzopyran glycoside. Compounds 4, 6-10, 12, and 13 were isolated for the first time from Gentiana plants. Compounds 1 and 2 showed promising hepatoprotective activity against D-GalN-induced AML12 cell damage at the concentration of 10 µmol·L~(-1), and compound 2 exhibited more significant activity than silybin at the same concentration.

Lignan glucosides from Gentiana macrophylla with potential anti-arthritis and hepatoprotective activities.

Ten lignans, including six previously undescribed phenolic ester glycosyl lignans (1-6), were isolated from a well-known traditional Chinese medicine, Qin-Jiao, which is the dry root of Gentiana macrophylla Pall. (Gentianaceae). Their structures were determined by spectroscopic and chemical methods, especially 2D NMR techniques. Quantum chemical calculations of theoretical ECD spectra allowed the determination of their absolute configurations. Refer to its traditional applications for the treatment of rheumatic arthralgia and hepatopathy, these compounds were evaluated on a TNF-α induced MH7A human synoviocyte inflammation model and a D-GalN induced AML12 hepatocyte injury model. Compounds 1, 2, 5, and 6 significantly reduced the release of proinflammatory cytokine IL-1ß in MH7A cells at 15 µM and they also could strongly protect AML12 cells against D-GalN injury at 30 µM. Flow cytometry and Western blot analysis showed that compound 5 ameliorated D-GalN induced AML12 cell apoptosis by upregulating the expression of anti-apoptotic Bcl-2 protein and down-regulating the expression of pro-apoptotic Bax protein.

Terpenoid Glucosides from Gentiana macrophylla That Attenuate TNF-α Induced Pulmonary Inflammation in A549 Cells.

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1ß and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.

Enantiomeric N-acetyldopamine trimers from Cicadae Periostracum and their absolute configurations.

Six previously undescribed N-acetyldopamine (NADA) trimmer racemates, percicamides A-F (1-6), were isolated from a 70% ethanol extract of Cicadae Periostracum. Subsequent chiral-phase separation afforded six pairs of enantiomers, (+)- and (-)-percicamides A-F (1a/1b-6a/6b). Their structures including absolute configurations were elucidated by combined extensive spectroscopic data and quantum chemical calculations. Compounds 1-6 represent the first examples of NADA trimmers with a cis-relationship of H-7'/H-8' or H-7''/H-8''. Bioassays verified that all isolated compounds showed weak inhibitory effects on nitric oxide production in RAW 264.7 cells.

α-Pyrones with glucose uptake-stimulatory activity from the twigs of Cryptocarya wrayi.

Five new α-pyrones, cryptowratones A-E (1-5), and five known congeners (6-10), together with four other known compounds 11-14 were isolated from the twigs of Cryptocarya wrayi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic data analysis and ECD calculations. All α-pyrones except 6 were evaluated for their stimulatory effects on glucose uptake in vitro with CHO-K1/GLUT4 cells. The positive control insulin displayed an approximate 42 ± 0.14% promotion on glucose uptake at 25 µM, compared with the CHO-K1/GLUT4 group. Compounds 1a/2a, 2, 3, and 10 showed a more significant stimulation of glucose uptake than insulin (25 µM) by 36 ± 0.08%, 27 ± 0.12%, 28 ± 0.12%, and 25 ± 0.12% at 1.5 µM, respectively. Immunofluorescence assays indicated the glucose uptake-stimulatory activity of α-pyrones might be correlated with increased GLUT4 translocation.

Two new isoquinoline alkaloids from Cryptocarya wrayi and their biological activities.

Two new isoquinoline alkaloids, cryptowrayines A (1) and B (2), along with one known pavine alkaloid (-)-12-hydroxyeschscholtzidine (3), were isolated from the twigs of Cryptocarya wrayi. The structures of new compounds were elucidated by extensive spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Both compounds 1 and 2 exhibited moderate quinone reductase inducing activity in Hepa 1c1c7 cells.

[A new phenylethanol glycoside from Baphicacanthis Cusiae Rhizoma et Radix].

The 95% ethanol extract of Baphicacanthis Cusiae Rhizoma et Radix was purified by multi-chromatographic methods including microporous resin, silica gel, Sephadex LH-20, and C_(18) reversed-phase column chromatography. Fourteen compounds were isolated and structurally identified, including five phenylethanoid glycosides, five phenylpropanoids, one lupinane triterpene, two alkaloids, and one flavonoid, listed as follows: 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol B(1), threo-2,3-bis-(4-hydroxy-3-methoxybenzene)-3-methoxypropanol(2), 2-(3-hydroxy-4-methoxyphenyl)-ethanol-1-O-[3,4-O-di-acetyl-(1→3)-O-α-L-rhamnopyranosyl]-ß-D-glucopyranoside(3), verbascoside(4), 2″,3″-di-O-acetyl martynoside(5),(+)-pinore-sinol(6), diospyrosin(7), daidzein(8), wiedemannioside B(9), buddlenol A(10), 2″-O-acetyl martyonside(11), lupeol(12), indirubin(13), and tryptanthrin(14). Compound 3 was a new phenylethanoid glycoside, and the other 10 compounds were isolated for the first time from Baphicacanthis Cusiae Rhizoma et Radix except compounds 12, 13, and 14.

Pseudosterins A-C, Three 1-Ethyl-3-formyl-ß-carbolines from Pseudostellaria heterophylla and Their Cardioprotective Effects.

Pseudostellaria heterophylla is used in China not only as a functional food but also as an herb to tonify the spleen, enhance immunity, and treat palpitation. Our previous investigation showed that a fraction enriched in glycosides obtained from the roots of P. heterophylla possessed pronounced protective effects on H9c2 cells against CoCl2-induced hypoxic injury. However, the active compounds responsible for the observed effects were still unknown. In the current investigation, pseudosterins A-C (1-3), three new alkaloids with a 1-ethyl-3-formyl-ß-carboline skeleton, together with polydatin, have been isolated from the active fraction. Their structures were elucidated on the basis of spectroscopic analysis and quantum chemical calculations. The four compounds showed cardioprotective effects against sodium hydrosulfite-induced hypoxia-reoxygenation injury in H9c2 cells, with the three alkaloids being more potent. This is also the first report of alkaloids with a ß-carboline skeleton isolated from P. heterophylla as cardioprotective agents.

[A new spirocyclic cycloartane triterpenoid from Souliea vaginata].

The 70% ethanol extract of the whole plant of Souliea vaginata was purified by multi-chromatographic methods including macroporous resin,silica gel,Sephadex LH-20,and C18-reversed-phase column chromatography. A new spirocyclic cycloartane triterpenoid was isolated and identified as( 16 R*,20 R*,23 S*,24 R*,25 S*)-16,23: 23,26-diepoxy-15α,24,25-trihydroxy-9,19-cycloart-3ß-O-ß-D-xylopyranoside( 1),and named as soulieoside S. Its planar structure and relative configuration were determined by spectroscopic techniques including 2 D NMR and HRESI-MS. As one of the main components of S. vaginata,compound 1 was evaluated for its anti-inflammatory activity by a lipopolysaccharide( LPS)-stimulated NO production model in RAW264. 7 macrophages,but it didn't show NO production inhibitory effect.

Benzofurans from Eupatorium chinense enhance insulin-stimulated glucose uptake in C2C12 myotubes and suppress inflammatory response in RAW264.7 macrophages.

Fourteen acetylbenzofuran derivatives, including three undescribed carbon skeletons with a newly formed hexane or benzene ring on the other side of the benzofuran ring, (±)-eupatonin A (1), (±)-eupatonin B (2), and eupatonin C (3), two new benzofurans (-)-12ß-hydroxygynunone (4) and (+)-12-hydroxyl-13-noreuparin (5), as well as 9 known ones (6-14), were isolated from 95% ethanol extract of the roots of Eupatorium chinense. Their structures were determined by spectroscopic methods and quantum chemical DFT and TDDFT calculations of the NMR chemical shifts and ECD spectra, which helped in the determination of the relative configurations of 1 and 2 and the absolute configurations of 4 and 5, respectively. 1 and 2 were further identified to be racemic mixtures by chiral HPLC analysis. All compounds were evaluated for insulin-stimulated glucose uptake in differentiated C2C12 myotubes. Compounds 1, 3, 4, 5, 11, 12, and 13 markedly enhanced insulin-mediated glucose uptake. (±)-Eupatonin A (1) activated the IRS-1/Akt/GSK-3ß signaling pathway and enhanced insulin stimulated GLUT4 membrane translocation in C2C12 myotubes. On LPS stimulated RAW264.7 macrophages, several compounds exhibited significant inhibitory effect on NO production with IC50 values ranging from 4.94 to 9.70 µΜ. (±)-Eupatonin A (1) again dose-dependently suppressed LPS-induced NO production and decreased the expression of inducible NO synthase (iNOS), through inhibiting NF-κB activity.

Triterpenoids from Cyclocarya paliurus that Enhance Glucose Uptake in 3T3-L1 Adipocytes.

Four previously undescribed compounds, including three rarely occurring seco-dammarane triterpenoid glycosides and a pentacyclic triterpenic acid, were isolated from a 70% ethanol extract of the leaves of Cyclocarya paliurus (Juglandaceae), along with eleven known triterpenoids. Their structures were determined by spectroscopic techniques, including 2D NMR and HRESIMS, as well as chemical methods. Among them, several triterpenoids enhanced insulin stimulated glucose uptake in both 3T3-L1 adipocytes and C2C12 myotubes. Furthermore, compound 1 dose-dependently increased glucose uptake through activating AMP-activated protein kinase (AMPK)-p38 pathway. Collectively, triterpenoids from C. paliurus could be developed as insulin sensitizers, which might have therapeutic potential for insulin resistance and hyperglycemia.

New podolactones from the seeds of Podocarpus nagi and their anti-inflammatory effect.

Podolactones are a class of structural diverse diterpenoid lactones, mainly isolated from the Podocarpus species. Several bioactivities have been disclosed for podolactones, including cytotoxicity and anti-atherosclerosis. In this study, the seeds of P. nagi were isolated by comprehensive chromatographic methods to obtain three new podolatones, named nagilactone B 1-O-ß-D-glucoside (1), nagilactone N3 3-O-ß-D-glucoside (2), and 2-epinagilactone B (3), as well as a known compound, nagilactone B (4). Their structures were determined by analyses of NMR and HRESIMS data. Compounds 1 and 2 significantly inhibited nitric oxide (NO) production on LPS-stimulated RAW264.7 macrophages, with IC50 values of 0.18 ± 0.04 and 0.53 ± 0.03 µM, respectively. Indomethacin (IC50 4.21 ± 0.32 µM) was used as a positive control. Compound 1 suppressed the expression of inducible NO synthase (iNOS) in a concentration-dependent manner, mediating through inhibiting nuclear factor-κB (NF-κB) activity. This is the first report regarding the anti-inflammatory effect of podolactones, which could be potential anti-inflammatory agents.

Terpenoids from Curcuma wenyujin increased glucose consumption on HepG2 cells.

Thirty four terpenoids, including two new cadinane-type sesquiterpenoids containing conjugated aromatic-ketone moieties, curcujinone A (1) and curcujinone B (2), were isolated from 95% ethanol extract of the root tubers of Curcuma wenyujin. Their structures were determined by spectroscopic methods, especially 2D NMR and HRMS techniques. The relative and absolute configurations of 1 and 2 were identified by quantum chemical DFT and TDDFT calculations of the 13C NMR chemical shifts, ECD spectra, and specific optical rotations. All compounds and extracts were evaluated for their anti-diabetic activities with a glucose consumption model on HepG2 Cells. The petroleum fraction CWP (10µg/mL) and compounds curcumenol (4), 7α,11α-epoxy-5ß-hydroxy-9-guaiaen-8-one (5), curdione (17), (1S, 4S, 5S 10S)-germacrone (18), zederone (20), a mixture of curcumanolide A (25) and curcumanolide B (26), gajutsulactone B (27), and wenyujinin C (30) showed promising activities with over 45% increasing of glucose consumption at 10µM.

Cephalotanins A-D, Four Norditerpenoids Represent Three Highly Rigid Carbon Skeletons from Cephalotaxus sinensis.

Four polycyclic norditerpenoids, cephalotanins A-D (1-4) representing three unprecedented carbon skeletons with highly rigid ring systems, were isolated from Cephalotaxus sinensis and structurally characterized by a combination of various methods. Compounds 1 and 2 are new skeletal norditerpenoid trilactones, while 3 and 4 are two norditerpenoids featuring different new carbon skeletons. Biosynthetic pathways for 1-4 were proposed by involving diverse and very fascinating chemical events with the coexisting cephalotane troponoids as the precursors. Compound 1 exhibited good NF-κB inhibition with an IC50 value of 4.12±0.61 µΜ.

Bioactive Phenanthrene and Bibenzyl Derivatives from the Stems of Dendrobium nobile.

A new enantiomeric pair of spirodiketones, (+)- and (-)-denobilone A (1 and 2), three new phenanthrene derivatives (3-5), and three new biphenanthrenes (22-24), along with 11 known phenanthrene derivatives (6-16), five known bibenzyl derivatives (17-21), and four known biphenanthrenes (25-28), were isolated from Dendrobium nobile. The structures of 1-5 and 22-24 were elucidated using comprehensive spectroscopic methods. (+)-Denobilone and (-)-denobilone A (1 and 2) were isolated as a pair of enantiomers by chiral HPLC. The absolute configurations of (+)- and (-)-denobilone A (1 and 2) were determined by comparing their experimental and calculated electronic circular dichroism spectra. The absolute configuration of denobilone B (3) was determined by X-ray crystallographic analysis. The inhibitory activities of all compounds against nine phytopathogenic fungi and three cancer cell lines were evaluated.

Ciliatonoids A and B, Two Limonoids from Toona ciliata.

Three new ring B-seco limonoids, ciliatonoids A-C (1-3), were isolated from Toona ciliate and structurally characterized by spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. Ciliatonoids A and B feature an unprecedented limonoid architecture, while ciliatonoid C belongs to a rare class of limonoids. Biological evaluation showed that compound 3 exhibited modest activities against the tested tumor cell lines.

Eucarobustols A-I, Conjugates of Sesquiterpenoids and Acylphloroglucinols from Eucalyptus robusta.

Nine new conjugates of sesquiterpenoids and acylphloroglucinols, named eucarobustols A-I (1-9), as well as 11 known analogues were isolated from the leaves of Eucalyptus robusta. The sesquiterpenoid motifs furnishing the new conjugates included four structural types of aristolane (1 and 2), guaiane (3), eudesmane (4), and aromadendrane (5-9) moieties. Compounds 1 and 2 were found to represent the first examples of conjugates of aristolane and acylphloroglucinol units. In turn, compound 3 features a new coupling model of guaiane and acylphloroglucinol via the C-4-C-7' bond. Compounds 1, 7, and 9 showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 1.3, 1.8, and 1.6 µM, respectively.

Antimalarial diterpenoid dimers of a new carbon skeleton from Aphanamixis grandifolia.

Chemical investigation into the minor constituents of Aphanamixis grandifolia yielded three new diterpenoid dimers, aphadilactones E-G (1-3) featuring a new carbon skeleton. Their structures and absolute configurations were fully established by comprehensive spectroscopic data analysis and ECD calculation. Discovery of another two new dimers (4 and 5) suggested the structure of recently reported aphanamene A to be re-investigated. Compounds 1-5 showed moderate antimalarial activities with low micromolar IC50 values.

Five new cycloartane triterpenoids from Beesia calthifolia.

Phytochemical study on rhizomes of Beesia calthifolia resulted in the isolation of five new (1-5) and three known (6-8) cycloartane triterpenoids possessing a hemiketal or ketal group at C-24 from the EtOAc fraction of 95% ethanol extract. Their structures were determined by spectroscopic and chemical methods, especially HRMS and 2D NMR techniques. Compounds 3 and 4 showed potential hepatoprotective activities against D-galactosamine induced human hepatic L02 cell damage.

Antibacterial Biphenanthrenes from the Fibrous Roots of Bletilla striata.

Four new 9',10'-dihydro-biphenanthrenes, including an unprecedented 1,2'-linked biphenanthrene, 4,7,3',5'-tetramethoxy-9',10'-dihydro(1,2'-biphenanthrene)-2,7'-diol (1), a new 1,3'-linked biphenanthrene, 4,7,7'-trimethoxy-9',10'-dihydro(1,3'-biphenanthrene)-2,2',5'-triol (2), and two new 1,1'-linked biphenanthrenes, 4,7,4'-trimethoxy-9',10'-dihydro(1,1'-biphenanthrene)-2,2',7'-triol (3) and 4,7,3',5'-tetramethoxy-9',10'-dihydro(1,1'-biphenanthrene)-2,2',7'-triol (4), as well as two known biphenanthrenes (5, 6), were isolated from a 95% ethanol extract of the fibrous roots of Bletilla striata. Their structures were determined by spectroscopic and spectrometric methods. Atropisomerism of these compounds was considered based on their chiral optical properties and potential energy surface scans at the ab initio HF/3-21G level, which revealed their racemic mixture form. Compounds 2-6 showed potent antibacterial activities against six Gram-positive bacterial strains.