Chaenomeles sinensis has been consumed traditionally for the treatment of throat diseases, diarrhea, inflammatory diseases, and dry beriberi. Repeated chromatography of the CHCl3-soluble fraction from the 80% MeOH extract of C. sinensis twigs led to the isolation of three new triterpenoids, sinenic acid A (1), 3β-O-cis-feruloyl-2α,19α-dihydroxyurs-12-en-28-oic acid (2), and 3β-O-cis-caffeoylbetulin (3), together with 20 analogues. The chemical structures of 1–3 were determined using diverse NMR techniques and HRMS data analysis, chemical methods, and computational approaches supported by advanced statistics (CP3). All the purified compounds were evaluated not only for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15) but for their potential neuroprotective effects through induction of nerve growth factor in C6 glioma cells. Their anti-inflammatory effects were also assessed by measuring nitric oxide levels in lipopolysaccharide-insulted murine microglia BV2 cells.

Four biflavonoid glycosides, balsamisides A–D (1–4), and nine known compounds (5–13) were obtained from the white petals of Impatiens balsamina. The 2D structures of the purified phytochemicals were established using conventional NMR techniques in addition to the new long-range HSQMBC NMR experiment. Acid hydrolysis followed by experimental and quantum-mechanics-based ECD data analysis permitted full configurational assignment of the purified metabolites. Compounds 1–13 were assessed for their potential to impede the generation of nitric oxide in lipopolysaccharide-stimulated BV2 cells. They were also investigated for potential neuroprotective activity using C6 cells and cytotoxicity against some human tumor cell lines, but were inactive (IC50 > 10 μM) against all the cell lines.

•Two new phenolic glycosides (1 and 2) and 11 known compounds (3–13) were isolated from the twigs of Spiraea prunifolia var. simpliciflora.•Their chemical structures were characterized via spectroscopic and computational methods.•The identified molecules exerted cytotoxic, anti-inflammatory, and neuroprotective activities.Quantum mechanics (QM)-based calculations for elucidating full structures of natural compounds are growing in importance and reliability. Two new phenolic glycosides (1 and 2) and 11 known compounds were isolated from the twigs of Spiraea prunifolia var. simpliciflora. The chemical structures of the new compounds (1 and 2) were initially established through different NMR techniques (1H and 13C NMR, COSY, HSQC, and HMBC), HRMS data analysis, and chemical hydrolysis. These structure assignments were further verified by QM-based NMR chemical shift calculations. All of the purified compounds (1–13) were evaluated for their cytotoxicity against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and BT549). Those phytochemicals were also evaluated for both anti-inflammatory activity through the measurement of nitric oxide (NO) production levels in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cell lines and neuroprotective effects via induction of nerve growth factor (NGF) in C6 glioma cells.Download high-res image (101KB)Download full-size image

•Eleven compounds including a new compound were isolated from Chaenomeles speciosa.•The chemical structures of the compounds were determined by NMR and MS analysis.•Compound 3 showed potent cytotoxic activity against the SK-MEL-2 cell line with IC50 values of 4.22 μM .•Compound 9 and 10 showed strong anti-inflammatory activity (IC50 2.38, and 6.70 μM).In our continuing search for bioactive constituents of Korean medicinal sources, we investigated an 80% MeOH extract of the twigs of Chaenomeles speciosa. Column chromatographic purification of the CHCl3 fraction resulted in the isolation of a new biphenyl derivative (1), along with four known biphenyl compounds (2–5) and six triterpenes (6–11). The chemical structure of the new compound was determined on the basis of spectroscopic analyses including 1D and 2D NMR data. Among isolates, compound 3 exhibited potent cytotoxic activities against SK-OV-3, SK-MEL-2, and XF498 cell lines (IC50 = 5.91, 4.22, and 6.28 μM, respectively). Also, Compounds 9 and 10 showed strong anti-neuroinflammatory activities (IC50 2.38, and 6.70 μM, respectively).Download high-res image (126KB)Download full-size image

Eleven new abietane-type diterpenes, holophyllins D–N (1–11), and 17 known analogues (12–28), were isolated from a MeOH extract of the trunk of Abies holophylla. The chemical structures of 1–11 were determined through spectroscopic data analysis, including NMR (1H and 13C NMR, DEPT, 1H–1H COSY, HMQC, HMBC, and NOESY) and HRFABMS methods. All isolated compounds (1–28) were evaluated for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-116), for their potential neuroprotective effects through induction of nerve growth factor in C6 glioma cells, and for their effects on nitric oxide levels in lipopolysaccharide-stimulated murine microglia BV2 cells.

Five new lignan glycosides, wasabisides A–E (1–5), and four known phenolic compounds (6–9), were isolated from the roots of Wasabia japonica. The chemical structures of the new compounds (1–5) were determined through spectroscopic analysis and chemical methods. All isolated compounds (1–9) were evaluated for their potential neuroprotective effects through induction of nerve growth factor in C6 glioma cells, for their effects on nitric oxide levels in lipopolysaccharide-stimulated murine microglia BV2 cells, and for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and BT549).

As part of our ongoing search for bioactive constituents of natural Korean medicinal plants, three new lignan derivatives, sambucasinol A–C (1–3), together with 7 known compounds (4–10) were isolated from the twigs of Sambucus williamsii. The structures of these new compounds were determined by a combination of 1D and 2D NMR spectroscopic data analysis, as well as circular dichroism (CD) spectroscopy studies. Here, we evaluated the anti-inflammatory effects of 1–10 in lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cells. Compounds 1–3 exhibited significant inhibitory effects on nitric oxide production in LPS-activated BV-2 cells, with IC50 values of 6.82, 7.04, and 14.70 μM, respectively. Additionally, we evaluated the effects of compounds 1–10 on NGF induction in a C6 rat glioma cell line. Compounds 1–3 upregulated NGF secretion to 183.95 ± 2.63%, 153.99 ± 5.15%, and 155.96 ± 5.15%, respectively, without any significant cell toxicity. Moreover, all isolates were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and XF498 cell lines. Compounds 1–3 showed consistent cytotoxicity against the four human cell lines, with IC50 values in the range of 11.07–19.62 μM.

The CHCl3 soluble fraction of the 80% MeOH extract of the stems of Firmiana simplex strongly inhibited nitric oxide production in lipopolysaccharide-activated BV-2 cells. A bioactivity-guided column chromatographic separation yielded two new lignans, firmianols A and B (1–2) together with seventeen known lignans (3–19). The structural elucidation of the new compounds was determined by spectroscopic methods, including 1D, 2D NMR and HR-FAB-MS. All isolated lignans were evaluated for their antineuroinflammatory effects on nitric oxide (NO) production in lipopolysaccharides (LPS)-activated murine microglia BV2 cells. Among the isolated, compounds 14 and 15 showed potent inhibitory activity against NO production (IC50 1.05 and 0.929 μM, respectively) without cell toxicity in murine microglia BV-2 cells. Compounds 11–13 and 17 also exhibited strong inhibitory effects on NO production, with IC50 values ranging from 7.07 to 15.28 μM.

Investigation of the MeOH extract of Chaenomeles sinensis twigs resulted in the isolation of seven biphenyl compounds (1–7) including a new compound, chaenomin (1). The chemical structures of the isolated compounds were elucidated by extensive NMR data (1H and 13C NMR, 1H–1H COSY, HSQC and HMBC), specific optical rotation, and chemical reaction. Compounds 2 and 6 showed potent cytotoxic activities against four cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15), and compound 7 exhibited potent anti-neuroinflammatory and NGF-potentiating activity.

⿢Three new lignans (1⿿3), together with nine known compounds (4⿿12) were isolated from Sinomenium acutum..⿢Their chemical structures were determined based on spectroscopic methods.⿢Compounds 1, 2, 7, and 8 significantly reduced LPS-induced NO levels in BV-2 cells.In our continuing search for bioactive constituents from Korean medicinal sources, an investigation of the Sinomenium acutum Rehder et Wilson rhizome afforded three new lignan derivatives (1⿿3) together with nine known compounds (4⿿12). The identification and structural elucidation of these new compounds were based on 1D and 2D-NMR (COSY, HMQC, HMBC and NOESY) and MS data. The absolute configurations were established based on the CD data. Nitric oxide production was evaluated in the BV-2 lipopolysaccharide-activated microglia cell line to investigate the anti-neuroinflammatory effects of the isolated compounds (1⿿12).

Phytochemical investigation of the bark from the stems of Sorbus commixta led to the isolation and characterization of a new fatty acid, sorcomic acid (1), along with nine known analogues (2–10). The structure of the new compound (1) was determined through NMR (1H and 13C NMR, HSQC, HMBC, and NOESY), MS, and specific optical rotation. The known compounds (2–10) were identified by comparison of their spectroscopic data with those in the literature. The biological activities of all the isolated compounds (1–10) were evaluated: compounds 1, 5, and 7 potently induced NGF secretion from C6 glioma cells (233.40 ± 12.82, 194.40 ± 8.05, and 185.74 ± 10.25 %, respectively) and compound 10 reduced NO levels with an IC50 value of 71.25 μM in murine microglia BV2 cells stimulated by LPS.

Phytochemical investigation of the twigs of Chaenomeles sinensis led to the isolation and identification of six new lignan glycosides, chaenomiside A–F (1–6), along with five known ones (7–11). Their chemical structures were determined by spectroscopic methods, including NMR, MS, ECD, and GC/MS analyses. All the isolated compounds (1–11) were tested for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide-activated murine microglial cells and the secretion of nerve growth factor (NGF) in a C6 rat glioma cell line. Compound 6 significantly reduced NO levels in the murine microglia BV2 cells with an IC50 value of 21.3 μM, and compounds 1, 3, and 6 were potent stimulants of NGF release with stimulation levels of 151.74 ± 6.77%, 144.31 ± 7.49%, and 167.61 ± 18.5%, respectively.

A bioassay-guided fractionation and chemical investigation of the MeOH extract of Raphanus sativus seeds resulted in the isolation and identification of eight phenylpropanoid sucrosides (1–8) including two new compounds, named raphasativuside A and B (1–2) from the most active CHCl3-soluble fraction. The structures of these new compounds were elucidated through spectral analysis, including extensive 2D-NMR data, and chemical reaction experiments. We evaluated the anti-inflammatory effects of 1–8 in lipopolysaccharide (LPS)-stimulated murine microglia BV2 cells. Compounds 2 and 5 exhibited significant inhibitory effect on nitric oxide production in LPS-activated BV-2 cells with IC50 values of 21.63 and 26.96 μM, respectively. All isolates were also evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15). Compounds 1–7 showed consistent cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC50 values of 6.71–27.92 μM. Additionally, the free-radical scavenging activity of 1–8 was assessed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay where compounds 1, 3, and 4 scavenged DPPH radical strongly with IC50 values of 23.05, 27.10, and 29.63 μg/mL, respectively.A bioassay-guided fractionation and chemical investigation of the MeOH extract of Raphanus sativus seeds resulted in the isolation and identification of eight phenylpropanoid sucrosides (1–8) including two new compounds, named raphasativuside A and B (1–2) from the most active CHCl3-soluble fraction.

•Thirteen phenolic compounds including two new compounds were isolated fromImpatiens balsamina.•Their chemical structures were determined based on spectroscopic methods.•New compound 1 exhibited a strong induction of NGF secretion by 155.59 ± 13.21%.•Compound 3 showed potent cytotoxic activity against the SK-MEL-2 cell line with IC50 values of 1.03 μM.During the course of our continuing search for biologically active compounds from Korean medicinal sources, we investigated the white flower of Impatiens balsamina. From the MeOH extract, two new phenolic compounds (1–2) containing a nitrile group and eleven known phenolic compounds (3–13) were isolated. The chemical structures of new compounds (1–2) were determined through NMR, HRMS, and CD data. We tested the isolated compounds (1–13) for their cytotoxic activities by determining their inhibitory effects on human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) in vitro using the sulforhodamine B (SRB) assay. We also investigated their neuroprotective activity by determining their effects on nerve growth factor (NGF) secretion in C6 cells, and anti-neuroinflammatory activity by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV-2 cells.

As a part of an ongoing search for bioactive constituents from Korean medicinal plants, the phytochemical investigations of the twigs of Salix glandulosa afforded 12 new phenolic glycosides (1–12) and a known analogue (13). The structures of 1–13 were characterized by a combination of NMR methods (1H and 13C NMR, 1H–1H COSY, HMQC, and HMBC), chemical hydrolysis, and GC/MS. The absolute configuration of 13 [(1R,2S)-2-hydroxycyclohexyl-2′-O-trans-p-coumaroyl-β-d-glucopyranoside] was determined for the first time. Compounds 1–3, 6, and 7 exhibited inhibitory effects on nitric oxide production in lipopolysaccharide-activated murine microglial cells (IC50 values in the range 6.6–20.5 μM).

In the search for antitumor compounds from Korean natural resources, activity-guided fractionation and purification processes were used on seeds of morning glory (Pharbitis nil). Air-dried P. nil seeds were extracted with ethanol and separated into n-hexane, chloroform, ethyl acetate, and n-butanol. Four new lignans, pharbilignans A–D (1–4) were isolated from the most active ethyl acetate fraction of the ethanol extract. Their structures were characterized on the basis of spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance (NMR) techniques, high resolution mass spectrometry (HRMS), and circular dichroism (CD) spectroscopy. The cytotoxic activities of the isolates (1–4) were evaluated by determining their inhibitory effects on four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15) using a sulforhodamine B (SRB) bioassay. Pharbilignan C (3) showed potent cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines with IC50 values of 1.42, 0.16, 0.20, and 0.14 μM, respectively. On the basis of the expanded understanding that inflammation is a crucial cause in tumor progress, we also evaluated anti-inflammatory activity of the isolates (1–4). Pharbilignan C (3) strongly inhibited nitric oxide (NO) production in the lipopolysaccharide (LPS)-activated BV-2 microglia cell line with an IC50 value of 12.8 μM.

Two new angucyclic quinones, angumycinones A (1) and B (2) and six known angucyclinone analogues (3–8) were isolated from a liquid culture extract of the Streptomyces sp. KMC004 strain from acidic coal mine drainage. The structures of these compounds were established using extensive spectroscopic data analyses, including NMR, HRFABMS, UV, CD, and X-ray crystallography. Compounds 1–8 were tested for antimicrobial activity against ten pathogenic microbial or fungal strains. Angumycinone B (2) exhibited antimicrobial activity against Micrococcus luteus, Enterococcus hirae, and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration values of 0.78, 1.56, and 12.5 μg/mL, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide

Six new lignans (1–6) were isolated from the trunk of Abies holophylla MAXIM, together with 11 known lignans (7–17). The structures of 1–7 were elucidated by spectroscopic methods, acid hydrolysis, and use of the modified Mosher’s method. The effects of the isolates on nerve growth factor induction in a C6 rat glioma cell line were evaluated. Compounds 6, 7, and 13 showed significant induction of nerve growth factor secretion at concentrations of 10 μM. Compounds 1, 5, 6, and 16 showed moderate inhibitory effects on nitric oxide production in lipopolysaccharide-activated BV-2 cells (IC50 28.5–36.4 μM).

In a continuing search for bioactive constituents from Dioscoreaceae medicinal plants, two new cyclic diarylheptanoids, diosniponol A (1) and B (2), together with 10 known compounds (3–12) were isolated from the rhizomes of Dioscorea nipponica. The structures of these new compounds were determined by spectroscopic analyses, including extensive two-dimensional nuclear magnetic resonance, high-resolution mass spectrometry, and optical rotation. All isolated compounds 1–12 were evaluated for their effects on nitric oxide (NO) production in murine microglia cell line BV-2. Compounds 8 and 11 showed potent inhibitory activities on NO production (IC50 13.36 and 14.36 μM, respectively) without cell toxicity in lipopolysaccharide-activated BV-2 cells.

•Two new steroidal saponins were isolated from the roots of Cynanchum paniculatum.•Structures of the new saponins were elucidated by spectroscopic analyses.•Cytotoxicity of the compounds was evaluated against four cancer cell lines in vitro.Two new steroidal saponins, cynanside A (1) and B (2) were isolated together with three known compounds (3–5) from the roots of Cynanchum paniculatum (Bunge) Kitag. The structures of 1 and 2 were elucidated on the basis of spectroscopic analyses, including extensive 2D NMR and acid hydrolysis. We evaluated the cytotoxicity of isolates (1–5) against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines in vitro using the SRB bioassay. Compounds 1 and 2 showed selective cytotoxicity against SK-MEL-2 cells with IC50 values of 26.55 and 17.36 μM, respectively.

Two previously unreported spiro-cyclopentenones, spirobacillenes A (1) and B (2), were isolated from the 24 h broth culture of Lysinibacillus fusiformis KMC003 derived from acidic coal-mine drainage. The structures of 1 and 2 were elucidated by analyses of the NMR, HRFABMS, single-crystal X-ray diffraction crystallography, and circular dichroism (CD) spectral data. Compound 1 possessed moderate inhibitory activity against the production of nitric oxide (NO) and reactive oxygen species (ROS).

•Nine steroidal compounds including five new compounds were isolated from Allium macrostemon.•Their chemical structures were determined based on spectroscopic methods.•The isolateds were tested for cytotoxicity against four human tumor cell lines in vitro.A new pregnane-type steroidal glycoside (1), two new spirostane-type steroidal glycosides (2, 3), and two new furostane-type steroidal glycosides (4, 5), named allimacrosides A–E, together with four known compounds (6–9) were isolated from a 80% MeOH extract of Allium macrostemon Bunge. The identification and structural elucidation of these compounds were based on their 1D- and 2D-NMR spectra, and HR-FAB-MS data analysis. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using the sulforhodamine B bioassay.Download high-res image (171KB)Download full-size image

BackgroundThe bulb of Fritillaria thunbergii has been utilised as mucoregulators and expectorants for controlling the airway inflammatory diseases in folk medicine.Hypothesis/PurposeWe investigated whether verticine, ebeiedine and suchengbeisine isolated from the bulbs of Fritillaria thunbergii inhibit the gene expression and production of MUC5AC mucin from human airway epithelial cells.Study designConfluent NCI-H292 cells were pretreated with verticine, ebeiedine or suchengbeisine for 30 min and then stimulated with EGF, PMA or TNF-α for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA.Results(1) Verticine, ebeiedine or suchengbeisine inhibited the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-α; (2) The production of MUC5AC mucin protein induced by EGF, PMA or TNF-α were also inhibited by treatment of verticine, ebeiedine or suchengbeisine.ConclusionThese results suggest that verticine, ebeiedine and suchengbeisine isolated from the bulbs of Fritillaria thunbergii inhibit the gene expression and production of MUC5AC mucin, by directly acting on airway epithelial cells, and the results are consistent with the traditional use of Fritillaria thunbergii as remedy for diverse inflammatory pulmonary diseases.Download high-res image (192KB)Download full-size image

Ethnopharmacological relevanceDioscorea nipponica (Dioscoreaceae) have been used as traditional medicines for diabetes, inflammatory and neurodegenerative diseases in Korea. The aim of the study was to isolate the bioactive components from the rhizomes of Dioscorea nipponica and to evaluate their anti-neuroinfalmmatory and neuroprotective activities.Material and methodsThe phytochemical investigation of 50% EtOH extract of Dioscorea nipponica using successive column chromatography over silica gel, Sephadex LH-20, and preparative high performance liquid chromatography (HPLC) resulted in the isolation and identification of 17 phenolic derivatives, including four new phenolic compounds (1–4). The structural elucidation of these compounds was based on spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy techniques, mass spectrometry, and optical rotation. All isolated compounds were evaluated for their effects on nerve growth factor (NGF) secretion in a C6 rat glioma cell line and nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 cells. The neurite outgrowth of compound 16 was further evaluated by using mouse neuroblastoma N2a cell lines.ResultsThree new stilbene derivatives, diosniponol C (1), D (2) and diosniposide A (3) and one new phenanthrene glycoside, diosniposide B (4), together with 13 known compounds were isolated from the rhizomes of Dioscorea nipponica. Of the tested compounds (1–17), phenanthrene, 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene (16) was the most potent NGF inducer, with 162.35±16.18% stimulation, and strongly reduced NO levels with an IC50 value of 19.56 μM in BV2 microglial cells. Also, it significantly increased neurite outgrowth in N2a cells.ConclusionsThis study supports the ethnopharmacological use of Dioscorea nipponica rhizomes as traditional medicine.Download high-res image (237KB)Download full-size image