Phytoecdysteroids from Dianthus superbus L.: Structures and anti-neuroinflammatory evaluation.

Six undescribed C27-phytoecdysteroid derivatives, named superecdysones A-F, and ten known analogs were extracted from the whole plant of Dianthus superbus L. Their structures were identified by extensive spectroscopy, mass spectrometric methods, chemical transformations, chiral HPLC analysis, and the single-crystal X-ray diffraction analysis. Superecdysones A and B possess a tetrahydrofuran ring in the side chain and superecdysones C-E are rare phytoecdysones containing a (R)-lactic acid moiety, whereas superecdysone F is an uncommon B-ring-modified ecdysone. Notably, based on the variable temperature (from 333 K to 253 K) NMR experiments of superecdysone C, the missing carbon signals were visible at 253 K and assigned. The neuroinflammatory bioassay of all compounds were evaluated, and 22-acetyl-2-deoxyecdysone, 2-deoxy-20-hydroxyecdysone, 20-hydroxyecdysone, ecdysterone-22-O-benzoate, 20-hydroxyecdysone-20,22-O-R-ethylidene, and acetonide derivative 20-hydroxyecdysterone-20, 22-acetonide significantly suppressed the LPS-induced nitric oxide generation in microglia cells (BV-2), with IC50 values ranging from 6.9 to 23.0 µM. Structure-activity relationships were also discussed. Molecular docking simulations of the active compounds confirmed the possible mechanism of action against neuroinflammations. Furthermore, none compounds showed cytotoxicity against HepG2 and MCF-7. It is the first report about the occurrence and anti-neuroinflammatory activity of the phytoecdysteroids in the genus Dianthus. Our findings demonstrated that ecdysteroids may be used as potential anti-inflammatory drugs.

Chemical characterization and multifunctional neuroprotective effects of sesquiterpenoid-enriched Inula britannica flowers extract.

Dried flowers of Inula britannica commercially serve as pharmaceutical/nutraceutical herbs in the manufacture of medicinal products and functional tea that has been reported to possess extensive biological property. However, the neuroprotective constituents in I. britannica flowers are not known. In the current study, phytochemicals of sesquiterpenoid-enriched I. britannica flowers extract and their potential multifunctional neuroprotective effects were investigated. Nineteen structurally diverse sesquiterpenoids, including two new sesquiterpenoid dimers, namely, inubritanolides A and B (1, 2), and four new sesquiterpenoid monomers (3-6), namely, 1-O-acetyl-6-O-chloracetylbritannilactone (3), 6-methoxybritannilactone (4), 1-hydroxy-10ß-methoxy-4αH-1,10-secoeudesma-5(6),11(13)-dien-12,8ß-olide (5) and 1-hydroxy-4αH-1,10-secoeudesma-5(6),10(14),11(13)-trien-12,8ß-olide (6), as well as 13 known congeners (7-19) were isolated from this source. The structures of compounds 1-6 were elucidated by 1D- and 2D- NMR and HR-ESI-MS data, and their absolute configurations were discerned by electronic circular dichroism (ECD) data analysis and single crystal X-ray diffraction. Interestingly, inubritannolide A (1) is a new type [4 + 2] Diels-Alder dimer featuring a hepta-membered cycloether skeleton. Most of the compounds showed potential multifunctional neuroprotective effects, including antioxidative, anti-neuroinflammatory, and microglial polarization properties. Specifically, 1 and 6 displayed slight strong neuroprotective potency against different types of neuronal cells mediated by various inducers including H2O2, 6-hydroxydopamine (6-OHDA), and lipopolysaccharide (LPS). Overall, this is the first report on multifunctional neuroprotective effects of sesquiterpenoid-enriched I. britannica flowers extract, which supports its potential pharmaceutical/nutraceutical application in neurodegenerative diseases.

Triterpenoid saponins from the roots of Psammosilene tunicoides.

Seven oleanane-type triterpenoid saponins, tunicosaponins B-D (1-3), F-I (4-7), along with eight known triterpenoid saponins (8-15), were isolated from the roots of Psammosilene tunicoides. The structures of compounds 1-7 were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and chemical methods. Triterpene glycosides have been considered as major active constituents of P. tunicoides. This work provides a more complete insight into the saponin constituents of P. tunicoides.

Picrotoxane Sesquiterpene Glycosides and a Coumarin Derivative from Coriaria nepalensis and Their Neurotrophic Activity.

Two picrotoxane sesquiterpene lactone glycosides, nepalactones A (1) and B (2), and one new coumarin, nepalarin (3), were isolated from the root barks of the poisonous plant Coriarianepalensis. Their structures were elucidated via HRESIMS and 1D and 2D NMR spectroscopic analyses, and further verified via transformation methods. In addition, compounds 1-3 and five semisynthetic congeners (1a-e) were assayed for the activity to induce neurite outgrowth in rat pheochromocytoma (PC12) cells. As a result, nepalactone A derivative 1c and nepalarin (3) significantly enhanced nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells.

Soluble epoxide hydrolase inhibitory and anti-inflammatory components from the leaves of Eucommia ulmoides Oliver (duzhong).

Eucommia ulmoides leaves have been used as a functional food and drink in China. The purpose of this study was to identify the bioactive constituents with soluble epoxide hydrolase (sEH) inhibitory activity and anti-inflammatory properties. Twenty-seven known compounds (1-27) were isolated from the leaves of E. ulmoides Oliver, and their structures were identified by NMR and ESIMS analysis; three of these, 2,5-dimethoxy-3-glucopyranosyl cinnamic alcohol (11), foliasalacioside E2 (26), and icariside F2 (27), were obtained from this plant for the first time. Compounds 1-7 exhibited soluble epoxide hydrolase (sEH) inhibitory activity at 100 µM; among them, quercetin (1) and kaempferol (5) displayed potential activities with IC50 values of 22.5 ± 0.9 and 31.3 ± 2.6 µM, respectively, with noncompetitive inhibition mode. Nuclear factor kappa B (NF-κB) inhibitory activity of the isolated compounds was evaluated by the NF-κB liciferase assay in HepG2 cells. Compounds 1, 9, 20, and 27 displayed potent NF-κB inhibitory effects, with IC50 values of 15.14 ± 2.29, 15.23 ± 2.34, 16.88 ± 2.17, and 16.25 ± 2.19 µM, respectively, whereas other compounds showed weak inhibition of NF-κB transcriptional activity ranging from 17.54 to 92.6 µM. A structure-activity relationship of flavonoids 1-9 was also discussed. The results obtained in this work might contribute to the understanding of pharmacological activities of E. ulmoides leaves and further investigation on its potential application values for food and drug.

Chemical constituents of Abies delavayi.

Systematic phytochemical investigations on Abies delavayi afforded 110 compounds, including 49 terpenoids, 13 lignans, 20 flavonoids, three coumarins, and 25 other chemical constituents. By detailed analysis of one- and two-dimensional NMR spectroscopic and high-resolution mass spectrometric data, 10 previously unreported compounds were identified: they comprised three sesquiterpenoids, two diterpenoids, one triterpenoid, one monoterpenoid, one flavonoid, and two phenols. These 10 compounds and some previously known ones were subjected to two cytotoxic bioassays against three human tumor cell lines and NO production inhibition on RAW264.7 macrophages, respectively. (25R)-24,25-Dihydroabieslactone had the strongest cytotoxic activity against Colo-205 cells with an IC50 value of 19.0±3.7µg/mL. (+)-T-cadinol, 8,11,13-abietatrien-15-ol-18-yl acetate, 18-acetoxy-13-epi-manool, imperatorin, bergapten, and 5,7-O-dimethyl poriol exhibited weak inhibitory activity against LPS-induced NO production in RAW264.7 macrophages with IC50 values of approximately 50µg/mL.

Semisynthesis and in vitro cytotoxic evaluation of new analogues of 1-O-acetylbritannilactone, a sesquiterpene from Inula britannica.

Semisynthetic analogues of the natural product 1-O-acetylbritannilactone (ABL), a sesquiterpene isolated from the medicinal plant Inula britannica, have been prepared and exhibited significant in vitro cytotoxic activities against four cell lines including three human cancer cell lines (HCT116, HEp-2 and HeLa) and one normal hamster cell line (CHO). Structure-activity relationships indicate that esterification of 6-OH (enhanced lipophilicity) and α-methylene-γ-lactone functionalities play important roles in conferring cytotoxicity. Among the tested compounds, 14 bearing a lauroyl group (12C) at the 6-OH position displayed most potent in vitro cytotoxic activity, with IC50 values between 2.91 and 6.78 µM, comparable to the positive control etoposide (VP-16, IC50 values between 2.13 and 4.79 µM). Moreover, the compound 14 triggered remarkable apoptosis at a low concentration, and induced cell cycle arrest in G2/M phase in HCT116 cells. The biological assays conducted with normal cells (CHO) revealed that all the synthetic compounds are no selective against cancer cell lines tested.

Semisynthesis and antifeedant activity of new derivatives of a dihydro-ß-agarofuran from Parnassia wightiana.

Five new derivatives (2-6) were semi-synthesized using compound 1, a dihydro-ß-agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as the starting material by acylation, oxidation, reduction, esterification, and amination, respectively. Structures of 2-6 were confirmed by 1D- and 2D-NMR and HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (1-6) were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant effects of compounds 2 and 4 were greater than the parent compound 1 whereas other compounds exhibited low to no feeding deterrent effects against third instar M. separata larvae in lab bioassays. Therefore, our results suggest that acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve the antifeeding effect. This preliminary information will be useful in designing new insect control agents against M. separata and other important pests.

Coumarins from Daphne feddei and their potential anti-inflammatory activities.

Chemical examination of the methanolic extract from the stem bark of Daphne feddei led to the isolation of three new dicoumarin glucosides (1-3), and eight known coumarins, dicoumarins and dicoumarin glucosides. Their structures were elucidated by extensive analysis of spectral data and comparison with the literature values. All compounds were tested for inhibitory activity against lipopolysaccharide-induced NO production in RAW 264.7 macrophages, and compounds 4 and 5 showed potent inhibitory activity with IC50 values of 0.161 and 0.127 µM, respectively.

Flavonoids from Daphne aurantiaca and their inhibitory activities against nitric oxide production.

Chemical examination of the methanolic extract from the stem bark of Daphne aurantiaca led to the isolation of three new flavonoids (1-3), and 29 known flavonoids. All 32 compounds were isolated for the first time from Daphne aurantiaca. The isolates were tested for inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 21 and 24 showed potent inhibitory activities against the production of NO with IC50 values of 0.006 and 0.076 µM, respectively.

New sesquiterpenoids from Ainsliaea macrocephala and their nitric oxide inhibitory activity.

Investigation of the ethanol extract of the whole plant of Ainsliaea macrocephala led to the isolation of five new sesquiterpenoids, namely ainsliadimer C (1), ainsliadimer D (2), ainsliaolide B (3), ainsliatone B (4), and ainsliaolide C (5), together with seventeen known sesquiterpenes and sesquiterpene glycosides (6- 22). Their structures were elucidated by spectroscopic methods. The relative stereochemistry of ainsliadimers C (1) and D (2) were further confirmed by single crystal X-ray diffraction analysis. Total extract of A. macrocephala and compounds 1- 22 were tested for inhibitory activity against the production of nitric oxide in RAW 264.7 cells stimulated by LPS, as well as for cytotoxicity against RAW 264.7 macrophages. Of all samples tested, purified compounds 4, 7, and 12 strongly inhibited the production of nitric oxide with IC50 values of 8.78, 2.50, and 7.11 µM, and simultaneously showed low cytotoxicity against RAW 264.7 macrophages.

Mono- and sesquiterpenoids, flavonoids, lignans, and other miscellaneous compounds of Abies georgei.

A systematic phytochemical investigation of the aerial parts of Abies georgei yielded nine new and 72 known compounds, including four monoterpenes, four sesquiterpenes, 25 flavonones, 14 lignans, and 34 other chemical constituents. The new compounds included two monoterpenes (1 and 2), two sesquiterpenes (3 and 4), three flavonones (5, 6, and 7), and two other components (8 and 9). Their chemical structures were established on the basis of various spectroscopic data. All the isolates were tested for antitumor and anti-inflammatory activities. The new compound 9,4'-dihydroxy-5,7-dimethoxy-8-methylchalcone (7) demonstrated a moderate antiproliferative effect on QGY-7703 tumor cells (IC (50)  = 17.6 µg/mL). The known compound isoferulaldehyde (67) exhibited the strongest inhibitory activity against lipopolysaccharide (LPS)-induced NO production in RAW 264.7 macrophages (IC (50) = 19.0 µg/mL). Abies georgei may be a significant source of beneficial pharmaceutical compounds.

Abiesatrines A-J: anti-inflammatory and antitumor triterpenoids from Abies georgei Orr.

A novel spiro-lanostane (abiesatrine A, 1) was isolated from the aerial parts of Abies georgei together with 9 new (abiesatrines B-J, 2-10) and 10 known triterpenes (11-20). The new structures were established by the extensive analysis of their spectroscopic data. The configuration of 1, featuring a unique spirolactone formed by C-13 and C-23 via oxygen-bridge, was confirmed by X-ray crystallography, and its biopathway was tentatively proposed. Among these isolates, compound 16 showed the strongest inhibitory activity against LPS-induced NO production in RAW264.7 macrophages (IC(50) = 8.9 microg mL(-1)). While compounds 1 and 20 exhibited potent anti-proliferative effects on QGY-7703 cells with IC(50) values of 9.3 and 7.6 microg mL(-1), respectively. Preliminary structure-activity relationship (SAR) investigations defined structural feature of the 24Z-olefinic bond key to the lanostane and cycloartane pharmacophore.

Terpenoids from Daphne aurantiaca and their potential anti-inflammatory activity.

Phytochemical examination of the methanolic extract from the stem bark of Daphne aurantiaca led to the isolation of six new sesquiterpenoids, dauca-3,11-dien-2alpha,15-diol (1), 3-oxoguai-4-ene-11,12-diol (2), 4alpha,5alpha,8alpha,11alphaH-3-oxoguai-1(10)-en-12,8-olide-7alpha-diol (3), 4alpha,5alpha,8alpha,11betaH-3-oxoguai-1(10)-en-12,8-olide-7beta-diol (4), 4alpha,5betaH-guai-9,7(11)-dien-12,8-olide-1alpha,8alpha-diol (5), 4alpha,5alphaH-guai-9,7(11)-dien-12,8-olide-1alpha,8alpha-diol (6), and a new diterpenoid, 12-O-benzoylphorbol 13-nonanoate (7), together with 10 known terpenoids. All compounds were tested for inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages. Compounds 7, 8, 9, 10, and 11 showed potent inhibitory activities against NO production with IC(50) values of 0.01, 0.01, 0.06, 0.07, and 0.03 microM, respectively.

Chemical constituents of Crinum asiaticum L. var. sinicum Baker and their cytotoxic activities.

A phytochemical investigation of the bulbs of Crinum asiaticum L. var. sinicum Baker resulted in the isolation of two new alkaloids, asiaticumines A and B (1 and 2, resp.), together with 21 known compounds, including nine alkaloids, four amides, five phenolic compounds, and three flavonoids. All 23 compounds were isolated for the first time from Crinum asiaticum L. var. sinicum Baker. Their structures were elucidated by spectroscopic methods. In addition, ten alkaloids, 1-10, were evaluated for their cytotoxic activities against human tumor cell lines A549, LOVO, HL-60, and 6T-CEM. Compounds 3, 4, and 7-10 selectively showed remarkable inhibition against one or more of the tested cell lines.

Two new spirobiflavonoids from Abies chensiensis with moderate NO production inhibitory activity.

Phytochemical investigation of the aerial parts of Abies chensiensis afforded two new (compounds 2 and 3) and 27 known compounds, including the related compound larixinol ( 1). The structures of spirobiflavonoids 1- 3 were established using 1D and 2D NMR spectroscopic techniques. In addition, the structure of larixinol ( 1) was confirmed by X-ray crystallographic analysis. Compounds 1- 3 were evaluated for inhibitory activities against LPS-induced NO production in macrophages. Larixinol ( 1) showed moderate effects, with an IC(50) value of 60.0 microg/mL. In addition, it did not show any cytotoxicity on RAW 264.7 macrophages at 100 microg/mL.

Tunicyclin A, the first plant tricyclic ring cycloheptapeptide from Psammosilene tunicoides.

A novel cycloheptapeptide, tunicyclin A, with a unique tricyclic ring cyclopeptide skeleton, was isolated from Psammosilene tunicoides. Its structure was elucidated by extensive NMR and MS analysis. Biogenetically, tunicyclin A might be derived from cyclo-(Pro(1)-Ser(2)-(gamma-keto-delta-aldehedyl-Glu(3))-Leu(4)-Val(5)-Gly(6)-Ser(7)) via two steps of nucleophilic addition.

Phenylpropanoids from Daphne feddei and their inhibitory activities against NO production.

Chemical examination of the methanolic extract from the stem bark of Daphne feddei led to the isolation of five new phenylpropanoids, 4,4'-dihydroxy-3,3'-dimethoxy-9-butoxy-9,9'-epoxylignan (1), 4,4'-dihydroxy-3,3'-dimethoxy-9-ethoxy-9,9'-epoxylignan (2), daphneresinol (3), armaosigenin (4), and isocubebin (5), together with 33 known phenylpropanoids. All 38 compounds were isolated for the first time from D. feddei. All compounds were tested for inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages. Compounds 2, 8, 9, 12, 13, and 15 showed potent inhibitory activities against the production of NO with IC(50) values of 0.091, 0.047, 0.005, 0.088, 0.004, and 0.074 µM/mL, respectively.

Yuzurimine-type alkaloids from Daphniphyllum yunnanense.

Five new yuzurimine-type alkaloids, yunnandaphnines A-E (2-6), together with two known analogues, macrodaphniphyllamine (1) and calycinine A (7), have been isolated from the leaves and twigs of Daphniphyllum yunnanense. The structures of the new alkaloids were elucidated by spectroscopic methods. Yunnandaphnine E (6) is a novel heptacyclic yuzurimine-type alkaloid with an oxazine ring.