New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production.

A new isopropyl chromone (1) and a new flavanone glucoside (2) together with eleven known compounds (3-13) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one (1), 5,7-dihydroxyflavanone 7-O-ß-D-(6''-O-galloylglucopyranoside) (2), strobopinin (3), demethoxymatteucinol (4), pinocembrin-7-O-ß-D-glucopyranoside (5), (2S)-hydroxynaringenin-7-O-ß-D-glucopyranoside (6), afzelin (7), quercetin (8), kaplanin (9), endoperoxide G3 (10), grasshopper (11), vomifoliol (12), litseagermacrane (13) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1, 2, 5, 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC50 values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 µM, respectively, while the IC50 values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 µM, compared to that of the positive control, NG -monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 32.50±1.00 µM.

Four New Flavonoid C-Glycosides Isolated from Achyranthes aspera and Their Nitric Oxide Production Inhibitory Activities.

A chemical study of the methanol extract of the aerial parts of Achyranthes aspera led to the isolation of four new flavonoid C-glycosides (1-4) along with eight known analogs (5-12). Their structures were elucidated by a combination of spectroscopic data analysis, HR-ESI-MS, 1D and 2D NMR spectra. All the isolates were evaluated their NO production inhibitory activity in LPS-activated RAW264.7 cells. Compounds 2, 4, and 8-11 showed significant inhibition with IC50 values ranging from 25.06 to 45.25 µM, compared to that of the positive control compound, L-NMMA, IC50 value of 32.24 µM, whereas the remaining compounds were weak inhibitory activity with IC50 values over 100 µM. This is the first report of 7 from Amaranthaceae family, and 11 from the genus Achyranthes.

Undescribed Phenolic Glycosides from Syzygium attopeuense and Their Inhibition of Nitric Oxide Production.

Four undescribed phenolic glycosides including three stilbene derivatives (1 and 3) and sodium salt of 3 (2), and a chalcone glycoside (4), together with thirteen known compounds (5-17) were isolated from the leaves of Syzygium attopeuense (Gagnep.) Merr. & L.M.Perry. Their chemical structures were elucidated to be (Z)-gaylussacin (1), 6''-O-galloylgaylussacin sodium salt (2), 6''-O-galloylgaylussacin (3), 4'-O-[ß-D-glucopyranosyl-(1→6)-glucopyranosyl]oxy-2'-hydroxy-6'-methoxydihydrochalcone (4), gaylussacin (5), pinosilvin 3-O-ß-D-glucopyranoside (6), myricetin-3-O-(2''-O-galloyl)-α-L-rhamnopyranoside (7), myricetin-3-O-(3''-O-galloyl)-α-L-rhamnopyranoside (8), myricetin-3-O-α-L-rhamnopyranoside (9), quercitrin (10), myricetin-3-O-ß-D-glucopyranoside (11), myricetin-3-O-ß-D-galactopyranoside (12), quercetin 3-O-α-L-arabinopyranoside (13), myricetin-3-O-2''-O-galloyl)-α-L-arabinopyranoside (14), (+)-gallocatechin (15), (-)-epigallocatechin (16), and 3,3',4'-trimethoxyellagic acid 4-O-ß-D-glucopyranoside (17) by the analysis of HR-ESI-MS, 1D and 2D NMR spectra in comparison with the previously reported data. Compounds 1-3, 5, and 6 significant inhibition of NO production in LPS-activated RAW264.7 cells, with IC50 values ranging from 18.37±1.38 to 35.12±2.53 µM, compared to a positive control (dexamethasone) with an IC50 value of 15.37±1.42 µM.

Four New Pentacyclic Triterpene Glycosides Isolated from the Fruits of Cryptolepis buchananii R.Br. ex Roem. & Schult and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells.

From the methanol extract of the Cryptolepis buchananii fruits, four undescribed pentacyclic triterpenene glycosides (1-4) and five known pentacyclic triterpenenes (5-9) were isolated. Their structures were determined to be uncargenin C 28-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl ester (1), 3-O-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl ester (2), 3-O-ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl ester (3), 3-O-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosylasiatic acid 28-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl ester (4), asiatic acid (5), 2α,3ß,23-trihydroxyoleana-11,13(18)-dien-28-oic acid (6), arjunolic acid (7), 6ß-hydroxyarjunolic acid (8), and actinidic acid (9) based on analyses of their HR-ESI-MS, 1D and 2D NMR spectra. All the isolates showed significantly NO production inhibition in LPS-activated RAW264.7 cells with the IC50 values ranging from 18.79 to 37.57 µM, compared to that of the positive control compound, dexamethasone, which showed IC50 value of 14.05 µM.

Amenyunnaosides A-C, Three New Neolignans Isolated from Amentotaxus yunnanensis and Their Anti-inflammatory Activities.

Phytochemical study on the leaves of Amentotaxus yunnanensis led to the isolation of seventeen phenolic compounds including sixteen neolignans and lignans, and one flavone glycoside. Three among the isolates were previously unreported neolignans and named as amenyunnaosides A-C, respectively. Their structures were elucidated by extensive analyses of HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The isolated neolignans potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values ranging from 11.05 to 44.07 µM, compared to that of the positive control compound, dexamethasone, IC50 value of 16.93 µM. Additionally, amenyunnaoside A dose-dependently reduced production of IL-6 and COX-2 but did not effect to that of TNF-α at concentrations of 0.8, 4, and 20 µM.

Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells.

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values from 21.4 to 30.3 µM.

Synthesis and Biological Evaluation of Diversified Hamigeran B Analogs as Neuroinflammatory Inhibitors and Neurite Outgrowth Stimulators.

We describe the efficient synthesis of a series of new simplified hamigeran B and 1-hydroxy-9-epi-hamigeran B norditerpenoid analogs (23 new members in all), structurally related to cyathane diterpenoid scaffold, and their anti-neuroinflammatory and neurite outgrowth-stimulating (neurotrophic) activity. Compounds 9a, 9h, 9o, and 9q exhibited moderate nerve growth factor (NGF)-mediated neurite-outgrowth promoting effects in PC-12 cells at the concentration of 20 µm. Compounds 9b, 9c, 9o, 9q, and 9t showed significant nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, of which 9c and 9q were the most potent inhibitors, with IC50 values of 5.85 and 6.31 µm, respectively. Two derivatives 9q and 9o as bifunctional agents displayed good activities as NO production inhibitors and neurite outgrowth-inducers. Cytotoxicity experiments, H2O2-induced oxidative injury assay, and ELISA reaction speculated that compounds may inhibit the TNF-α pathway to achieve anti-inflammatory effects on nerve cells. Moreover, molecular docking studies provided a better understanding of the key structural features affecting the anti-neuroinflammatory activity and displayed significant binding interactions of some derivatives (like 9c, 9q) with the active site of iNOS protein. The structure-activity relationships (SARs) were also discussed. These results demonstrated that this structural class compounds offered an opportunity for the development of a new class of NO inhibitors and NGF-like promotors.

Cryptobuchanosides A-G: seven previously undescribed triterpene glycosides from Cryptolepis buchananii R.Br. ex Roem. and Schult. with nitric oxide production inhibition activity.

In this study, nine triterpene glycosides including seven previously undescribed compounds (1-7), were isolated from leaves of Cryptolepis buchananii R.Br. ex Roem. and Schult. using various chromatographic methods. The chemical structures of the compounds were elucidated to be 3-O-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (1), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (2), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosyluncargenin C 28-O-ß-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (3), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosylhederagenin 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (4), 3-O-ß-D-glucopyranosylarjunolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (5), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß- D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (6), 3-O-ß-D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (7), asiatic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (8), and 3-O-ß-D-glucopyranosylasiatic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (9), through infrared, high-resolution electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance spectral analyses. The isolates inhibited nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 18.8-58.5 µM, compared to the positive control compound, dexamethasone, which exhibited an IC50 of 14.1 µM.

Undescribed (2-7')-neolignans and polyoxygenated cyclohexene glycosides from the aerial parts of Piper mutabile C. DC. and their inhibitory effects on nitric oxide production.

A phytochemical study of the aerial parts of Piper mutabile C. DC. revealed seven undescribed compounds [two (2-7')-neolignans and five polyoxygenated cyclohexene glycosides] and six known propenylcatechol derivatives. The chemical structures of the isolated compounds were elucidated by extensive HR-ESI-MS and NMR analyses, as well as comparison with the literature. The absolute configurations of the (2-7')-neolignans were confirmed by GIAO 13C NMR calculations with a sorted training set strategy and TD-DFT calculation ECD spectra. The (2-7')-neolignans and polyoxygenated cyclohexene glycosides are unusual in natural sources. Undescribed neolignans 1 and 2 inhibited NO production in RAW 264.7 cells, with respective IC50 values of 14.4 and 9.5 µM.

Undescribed 2,9-deoxyflavonoids and flavonol-diamide [3+2] adduct from the leaves of Aglaia odorata Lour. Inhibit nitric oxide production.

Phytochemical study on the methanol extract of Aglaia odorata leaves resulted in the isolation of four previously undescribed compounds, including three 2,9-deoxyflavonoids and one flavonol-diamide [3 + 2] adduct, and 13 known compounds. The chemical structures of the four undescribed compounds were elucidated on the basis of their IR, HR-ESI-MS, 1D and 2D NMR, and ECD spectra. The results revealed an unprecedented 2,9-deoxyflavonoid framework, which was confirmed by TD-DFT, ECD, and GIAO 13C-NMR calculations using sorted training set methods. The 17 compounds were examined for their ability to inhibit NO production activity in cultured lipopolysaccharide-activated RAW264.7 cells with aglaodoratas A-C, odorine, and epi-odorine inhibiting NO production, with IC50 values in the range of 16.2-24.3 µM. The other investigated compounds had either weak or no activity.

Polypunctosides E-K: seven new steroidal saponins from Polygonatum punctatum Royle ex Kunth and their nitric oxide production inhibitory activities.

Polygonatum punctatum Royle ex Kunth is a high-value medicinal plant found in old natural forests. A phytochemical study on the roots of this plant led to the isolation of seven new steroidal saponins including four furostans (1-4) and three furospirostans (5-7). Their structures were elucidated as (25R)-26-O-(ß-D-glucopyranosyl)-furost-5-ene-3ß,17α,22α,26-tetraol 3-O-α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)-ß-D-galactopyranoside (1), (25R)-26-O-(ß-D-glucopyranosyl)-furost-5-ene-3ß,14α,17α,22α,26-pentaol 3-O-α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)-ß-D-galactopyranoside (2), (25R)-26-O-(ß-D-glucopyranosyl)-furost-5-ene-22α-methoxy-3ß,17α,26-triol 3-O-α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)-ß-D-galactopyranoside (3), (25R)-26-O-(ß-D-glucopyranosyl)-furost-5-ene-22α-methoxy-3ß,17α,26-triol 3-O-[α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)]-[acetoxy-(→ 6)]-ß-D-galactopyranoside (4), 26-O-(ß-D-glucopyranosyl)-14α,17α-dihydroxynuatigenin 3-O-α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)-ß-D-galactopyranoside (5), 26-O-(ß-D-glucopyranosyl)-17α-hydroxynuatigenin 3-O-α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)-ß-D-galactopyranoside (6), and 26-O-(ß-D-glucopyranosyl)-14α-hydroxynuatigenin 3-O-α-L-arabinopyranosyl-(1 → 2)-ß-D-glucopyranosyl-(1 → 4)-ß-D-galactopyranoside (7) by extensive spectroscopic analyses, including infrared, high-resolution electrospray ionization mass spectrometry, and one- and two-dimensional nuclear magnetic resonance spectroscopy. Compounds 1-7 inhibited nitric oxide production in lipopolysaccharide activated RAW264.7 cells with IC50 values ranging from 41.5 ± 3.2 to 62.2 ± 3.7 µM, compared to 33.8 ± 2.6 µM for the positive control compound L-NMMA.

Two new chlorinated sesquiterpenes from Sigesbeckia orientalis.

Two new chlorinated guaianane-type sesquiterpenes (named chlosigesolides A and B) together with eight known compounds were isolated from the leaves and twigs of Sigesbeckia orientalis. Their structures were determined by analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data as well as comparison with the literature. Absolute configurations of new compounds were elucidated by NOESY and ECD methods. Chlosigesolide A inhibited NO production in LPS-stimulated RAW264.7 macrophages with IC50 value of 10.9 ± 0.8 µM. Other compounds exhibited inhibitory activity at IC50 in range of 26.5 to 49.7 µM.

New nitric oxide production inhibitors from Syzygium bullockii.

Three undescribed triterpene glycosides syzybullosides A-C (1-3) along with fourteen known compounds were isolated from the leaves of Syzygium bullockii (Hance) Merr.& L.M. Perry, including six triterpene glycosides (1-6), four phenolics (7-9, 17), four megastigmanes (10-13), and three flavonoids (14-16). The structures of 1-17 were elucidated by extensive spectroscopic analysis, including IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1-10 and 12-17 inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW264.7 cells with IC50 values ranging from 1.30 to 13.70 µM, lower than that of the positive control compound, L-NMMA (IC50 = 33.8 µM).

New sesquiterpene and flavone arabinofuranoside derivative from the leaves of Fissistigma bicolor.

A new muurolane-type sesquiterpene, a new flavone arabinofuranoside derivative, and other five known flavone arabinofuranoside derivatives were isolated from the leaves of Fissistigma bicolor (Annonaceae family). Their chemical structures were determined to be (1S,6R,7S)-muurola-4,10(14)-diene-15-ol (1), quercetin 3-O-ß-D-apiofuranosyl-(1→2)-α-L-arabinofuranoside (2), quercetin 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinofuranoside (3), quercetin 3-O-α-L-arabinofuranoside (4), kaempferol 3-O-ß-D-apiofuranosyl-(1→2)-α-L-arabinofuranoside (5), kaempferol 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinofuranoside (6), and kaempferol 3-O-α-L-arabinofuranoside (7) by analyses of HR-ESI-MS and NMR spectral data. Compounds 4 and 7 containing monosaccharide, arabinofuranoside, potentially inhibited NO productions in LPS activated RAW264.7 cells (IC50 13.4 ± 0.5 and 12.6 ± 0.4 µM) in compared to disaccharide derivatives (IC50 ranging from 58.9 ± 3.3 to 65.6 ± 3.8 µM).

Pandatonkinosides A and B: two new phenolic glycosides from the roots of Pandanus tonkinensis and their nitric oxide production inhibitory activities.

Two new phenolic glycosides, 4-(3-hydroxypropyl)-2,6-dimethoxyphenol ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (1), trans-cinnamyl alcohol 9-O-(6'-O-ß-D-apiofuranosyl)-ß-D-glucopyranoside (2), together with nine known phenolic glycosides (3-11) were isolated from the roots of Pandanus tonkinensis. Their structures were determined by extensive analysis of HRESIMS and NMR spectral data, as well as by comparison of their spectral data (including CD spectra) with those reported in the literature. Compounds 1-4 and 6-11 inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 0.80 ± 0.06 µM to 43.38 ± 3.92 µM, whereas compound 5 was inactive. The NO production inhibitory activities of compounds 1, 4, 8, and 10 with IC50 values of 10.16 ± 1.05, 0.80 ± 0.06, 1.10 ± 0.13, and 2.79 ± 0.21 µM, respectively, are as potent as that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 9.80 ± 0.78 µM.

Kadsindutalignans A-C: three new dibenzocyclooctadiene lignans from Kasura induta A.C.Sm. and their nitric oxide production inhibitory activities.

Phytochemical study on the methanol extract of the stems and leaves of Kadsura induta led to the isolation of six dibenzocyclooctadiene lignans, including three new compounds named kadsindutalignans A-C (1-3), and three known ones, heteroclitalignan B (4), kadsuphilin C (5) and kadsulignan E (6). Their structures were elucidated based on extensive spectroscopic analyses, including HRESIMS, 1D- (1H NMR and 13C NMR), 2D-NMR (HSQC, HMBC, 1H-1H COSY and NOESY), and experimental circular dichroism (CD) spectra. All the isolates inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 5.67 ± 0.54 µM to 38.19 ± 2.03 µM, compared to that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA) with an IC50 value of 8.90 ± 0.48 µM. Interestingly, the new compound 2 showed potential inhibition of NO production with an IC50 value of 5.67 ± 0.54 µM, which was higher than that of the positive control.

A Review of Anti-inflammatory Terpenoids from the Incense Gum Resins Frankincense and Myrrh.

Frankincense and myrrh have been used as incense in religious and cultural ceremonies since the beginning of written history. Their common medicinal properties are used in the treatment for inflammatory conditions, some cancerous diseases, and wound healing. In the course of our characterization of the anti-inflammatory constituents from frankincense and myrrh, several terpenoid constituents were found to inhibit nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. Here we review the structure of those terpenoid constituents from the gum resins of frankincense and myrrh and evaluate their anti-inflammatory effects by their nitric oxide production inhibitory activity.