Dihydrophenanthro[b]furan derivatives from the tubers of Bletilla striata.

Two pairs of new dihydrophenanthro[b]furan enantiomers blephebibnols G-H (1-2), one new dihydrophenanthro[b]furan derivative blephebibnol I (3), along with four known analogues (4-7), were isolated from the tubers of Bletilla striata. Their structures including the absolute configurations were determined by the combination of spectroscopic data analysis, ECD and NMR calculations. Compounds 1a, 1b, and 2b showed inhibition of NO production in LPS-stimulated BV-2 cells, with IC50 values ranging from 4.11 to 14.65 µM. Further mechanistic study revealed that 1a suppressed the phosphorylation of p65 subunit to regulate the NF-κB signaling pathway. In addition, some compounds displayed selective cytotoxic activities against HCT-116, HepG2, A549, or HGC27 cancer cell lines with IC50 values ranging from 0.1 to 8.23 µM.

Neuroprotective and anti-inflammatory phenylethanoidglycosides from the fruits of Forsythia suspensa.

Neuroinflammation is emerging as a crucial reason of major neurodegenerative diseases in recent years. Increasingly evidences have supported that bioactive natural products from traditional Chinese medicines have efficiency for neuroinflammation. Forsythia suspensa, a typical medicinal herb, showed potential neuroprotective and anti-inflammatory properties in previous pharmacological studies. In our research to obtain neuroprotective and anti-inflammatory natural products, three unprecedented C6-C7'/C6-C16' linked phenylethanoidglycoside dimers (1-3), three new phenylethanoidglycosides (4-6), and six known compounds (7-12) were isolated from the fruits of Forsythia suspensa. Their structures were determined by comprehensive spectroscopic data and comparison to the literature data. All isolated compounds were evaluated their neuroprotective and anti-inflammatory activities. Compounds 1 and 10 exhibited significant neuroprotective activities with the cell viability values of 75.24 ± 8.05% and 93.65 ± 10.17%, respectively, for the serum-deprivation and rotenone induced pheochromocytoma (PC12) cell injury. Meanwhile, compound 1 exhibited excellent anti-inflammatory activity against tumor necrosis factor (TNF)-α expression in LPS induced RAW264.7 cells with the IC50 value of 1.30 µM. This study revealed that the bioactive phenylethanoidglycosides may attenuate neuroinflammation through their neuroprotective and anti-inflammatory activities.

Sesquiterpenoids, phenolic and lignan glycosides from the roots and rhizomes of Clematis hexapetala Pall. and their bioactivities.

Approximately 17 compounds were isolated from a 60% EtOH aqueous extract of the roots and rhizomes of Clematis hexapetala Pall., including three new guaianolide sesquiterpenoids with 5/7/5-fused rings and 3S-configuration (1-3), five new prenylated tetra-substituted phenolic glycosides (4-8) with 6/6-fused 9H-benzopyran skeleton (5) and 6/7-fused 7,10-dihydro-benzoxepin skeleton (6-8), one new isoferulyl glucoside (9), two new furofuran lignan diglucosides (10-11), and six known compounds. The chemical structures of the new compounds were elucidated via spectroscopic data and electronic circular dichroism (ECD) analyses in combination with a modified Mosher's method. The possible biosynthetic relationships of prenylated tetra-substituted phenols were postulated. In the in vitro assays, compound 16 exhibited moderate TNF-α secretion inhibitory activity with IC50 value of 3.419 µM. Compounds 14-16 displayed potent PTP1B enzymatic inhibitory activities with inhibition ratios of 48.30-86.00%. And compound 16 showed significant PTP1B enzymatic inhibition with IC50 value of 4.623 µM.

Two new lignans from the fruits of Forsythia suspensa.

Two new lignans, wikstronoside B (1) and forsysesquinorlignan (2), were isolated from the fruits of Forsythia suspensa, along with two known sesquineolignans, hedyotol A and hedyotol C (3 and 4). The structures of new compounds were established via extensive spectroscopy techniques, including UV, IR, HRESIMS, NMR, and ECD. Compounds 3 and 4 were isolated from this plant for the first time. Their anti-inflammatory effects were evaluated via a detection model with LPS-induced murine macrophage RAW264.7 cells, and compound 3 showed a moderate activity.

Anti-inflammatory phenylpropanoid glycosides from the fruits of Forsythia suspensa.

Five new phenylpropanoid glycosides, susaroysides A-E (1-5) were isolated from the fruits of Forsythia suspensa. Their structures were elucidated by comprehensive spectroscopic data analysis. The absolute configurations of their sugars were determined by GC analysis. Notably, susaroysides A-D possessed a sugar with an unsubstituted anomeric carbon, which is relatively rare in natural sources. Compound 1 exhibited significant anti-inflammatory activity against the lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α expression in macrophage cells with the IC50 value of 1.053 µM.

Phenanthrenequinone enantiomers with cytotoxic activities from the tubers of Pleione bulbocodioides.

Eight new phenanthrenequinones (four pairs of enantiomers), named bulbocodioidins A-D (1-4), have been isolated from the ethanolic extract of tubers of Pleione bulbocodioides. Their structures, including absolute configurations, were determined by extensive NMR analysis combined with experimental and calculated ECD (electronic circular dichroism) data analyses. Compounds 1-4 possessed a 9(10)H-phenanthren-10(9)-one structure, which is a rarely reported instance from natural sources. Their possible biosynthetic pathway was discussed in the text. The cytotoxic effects of the isolated phenanthrenequinones were evaluated in several human cancer cell lines, and compounds 1a and 4a exhibited marked cytotoxic activities.

An Efficient Method for Determining the Relative Configuration of Furofuran Lignans by 1H NMR Spectroscopy.

An efficient 1H NMR spectroscopic approach for determining the relative configurations of lignans with a 7,9':7',9-diepoxy moiety has been established. Using the chemical shift differences of H2-9 and H2-9' (ΔδH-9 and ΔδH-9'), the configurations of 8-H and 8-OH furofuran lignans can be rapidly and conveniently determined. The rule is applicable for data acquired in DMSO- d6, methanol- d4, or CDCl3. Notably, the rule should be applied carefully when the C-2 or C-6 substituent of the aromatic rings may alter the dominant conformers of the furofuran moiety.

Forsythenethosides A and B: two new phenylethanoid glycosides with a 15-membered ring from Forsythia suspensa.

Forsythenethosides A (1) and B (2), two new phenylethanoid glycosides with an unprecedented 15-membered carbon scaffold ring, were isolated from the fruits of Forsythia suspensa. Their structures, including their geometric configurations, were determined via extensive NMR spectroscopy techniques, especially using 2D NMR data combined with systematic conformational analysis. Forsythenethosides A and B showed strong neuroprotective activities against serum-deprivation-induced PC12 cell damage. Furthermore, they were active on rotenone-induced PC12 cell damage.

New iridoid glycosides from the fruits of Forsythia suspensa and their hepatoprotective activities.

A novel iridoid glycoside trimer named forsydoitriside A (1) and five new iridoid glycosides (2-6) were isolated from the fruits of Forsythia suspensa together with two known compounds (7, 8). These new structures were elucidated by comprehensive spectroscopic data and the comparison of experimental and calculated electronic circular dichroism spectra. Compounds 1-8 were all assayed on acetaminophen-induced HepG2 cell damage. The results exhibited that compounds 2, 3, 5 and 6 possessed strong hepatoprotective activities against the damage in HepG2 cell.

Forsythoneosides A-D, Neuroprotective Phenethanoid and Flavone Glycoside Heterodimers from the Fruits of Forsythia suspensa.

Forsythoneosides A-D (1-4), four unusual adducts of a flavonoid unit fused to a phenylethanoid glycoside through a pyran ring or carbon-carbon bond, and four new phenylethanoid glycosides (5-8) were isolated from the fruits of Forsythia suspensa, together with nine known compounds. The structures of 1-8, including their absolute configurations, were elucidated by spectroscopic data as well as experimental and calculated electronic circular dichroism analysis. Compounds 2 and 4 inhibited PC12 cell damage induced by rotenone, and increased cell viability from 53.9 ± 7.1% to 70.1 ± 4.0% and 67.9 ± 5.2% at 0.1 µM, respectively.

Phenolic glycosides and indole alkaloids isolated from the roots and rhizomes of Clematis chinensis and their anti-inflammatory activity.

Six undescribed compounds, including three phenolic glycosides (1-3) and three indole alkaloids (4-6), together with ten known alkaloids (7-16) and three known phenolic glycosides (17-19), were isolated from 70% EtOH aqueous extracts of the roots and rhizomes of Clematis chinensis Osbeck. The structures were elucidated by NMR, HRESIMS and X-ray diffraction spectroscopies. The anti-inflammatory activity of these compounds was evaluated, and twelve compounds showed significant inhibitory activity against TNF-α with an inhibition ratio from 47.87% to 94.70% at a dose of 10 µM. Compound 7 exhibited significant inhibitory activity against TNF-α and IL-6 with IC50 values of 3.99 µM and 2.24 µM, respectively. Compound 8 displayed potent anti-inflammatory activity against mouse ear edema induced by croton oil. A mechanistic study suggested that compounds 7 and 8 decreased the activation of the NF-κB signaling pathway to reduce the secretion of inflammatory factors in LPS-induced RAW 264.7 cells.

Two new phenylpropanoid glycosidic compounds from the pseudobulbs of Pleione bulbocodioides and their hepatoprotective activity.

Two new phenylpropanoid glycosidic compounds (a pair of epimers), named pleionosides K (1) and L (2), were isolated from the pseudobulbs of Pleione bulbocodioides (Franch.) Rolfe. Their structures, including absolute configurations, were elucidated by a combination of MS, NMR data, chemical methods and the comparison of experimental and calculated electronic circular dichroism (ECD). Their possible biosynthetic pathway was discussed in the text. Furthermore, the two compounds exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in in vitro assays, with cell survival rates of 25.83% and 28.82% at 10 µM, respectively, and antioxidant effect against H2O2-induced toxicity in human SK-N-SH cell, with increasing viability at 10 µM of 24.9% and 34.6%, respectively.

New triterpenoid saponins from the leaves of Ilex chinensis and their hepatoprotective activity.

Seven new triterpenoid saponins, including five ursane-type saponins, ilexchinenosides R-V (1-5), and two oleanane-type saponins, ilexchinenosides W-X (6-7), with four known triterpenoid saponins (8-11) were isolated from the leaves of Ilex chinensis. Their structures were elucidated by comprehensive spectroscopic 1D and 2D NMR and HR-ESI-MS data. Their sugar moieties were determined by HPLC analysis compared with standards after hydrolysis and derivatization. Compounds 1, 2, 4, 9 and 10 exhibited potential hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell injury in vitro.

Phenanthrene, 9,10-dihydrophenanthrene and bibenzyl enantiomers from Bletilla striata with their antineuroinflammatory and cytotoxic activities.

Thirteen undescribed phenanthrene and bibenzyl derivatives, named blestanols A-M, including one pair of biphenanthrene enantiomers, two bis 9,10-dihydrophenanthrene ethers, five pairs of 9,10-dihydrophenanthrene/bibenzyl atropisomers, one racemic 9,10-dihydrophenanthrene/bibenzyl dimer, one 9,10-dihydrophenanthrenebibenzyl ether, two pairs of bibenzyl derivatives, and one stilbene, together with 12 known analogues were isolated from the tubers of Bletilla striata. The structures were elucidated via spectroscopic data analysis. 15 compounds were purified to yield enantiomers (a, b) via chiral-phase HPLC, and their configurations were determined by optical rotation values and the comparison of the experimental and calculated electronic circular dichroism (ECD) curves. Blestanols K-L possessed a cycloheptene moiety, which is rarely observed in bibenzyl derivatives. A putative biosynthetic pathway for the identified components is deduced. Among these compounds, 14 compounds showed inhibition of NO production, with IC50 values ranging from 5.0 to 19.0 µM. Eight compounds displayed selective cytotoxic activities against HCT-116, HepG2, BGC-823, A549 or U251 cancer cell lines, with IC50 values ranging from 1.4 to 8.3 µM. In addition, their structure-activity relationships are discussed briefly.

Hepatoprotective lignans and triterpenoids from the roots of Kadsura longipedunculata.

Two new tetrahydrobenzocyclooctabenzofuranone lignans (1-2), a new dibenzocyclooctadiene lignan (3) and three new schiartane-type triterpenoids (4-6), together with six known compounds (7-12), were isolated from the roots of Kadsura longipedunculata. Their structures were elucidated by extensive NMR and HRESIMS spectroscopic data analysis. The absolute configurations of these compounds were determined by comparison of the experimental and calculated ECD spectra. Compound 12 exhibited moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells with cell survival rates of 53.04%.

Atropisomeric bi(9,10-dihydro)phenanthrene and phenanthrene/bibenzyl dimers with cytotoxic activity from the pseudobulbs of Pleione bulbocodioides.

Bulbocodioidins E-H (1-4), four pairs of undescribed racemic bi(9,10-dihydro)phenanthrene and phenanthrene/bibenzyl atropisomers, along with four known compounds (5-8) were isolated from the ethanol extract of the pseudobulbs of Pleione bulbocodioides. Their structures were established by HRESIMS and comprehensive NMR spectroscopic data analysis. Their absolute configurations were elucidated by comparison of their experimental and calculated ECD (electronic circular dichroism) curves. Furthermore, compound 4a displayed cytotoxic activity against colon cancer (HCT-116), liver cancer (HepG2), and breast cancer (MCF-7) cell lines with IC50 values of 7.6, 3.8 and 3.4 µM, respectively. Compound 6 showed cytotoxic activity against breast cancer cell lines (MCF-7) with IC50 value of 5.4 µM.

Eight new phenylethanoid glycoside derivatives possessing potential hepatoprotective activities from the fruits of Forsythia suspensa.

In our study to investigate components with hepatoprotective activities, eight new phenylethanoid glycoside derivatives (1-8) were isolated from the 75% EtOH-H2O extract of the fruits of Forsythia suspensa along with six known compounds (9-14). These new structures were elucidated through HRESIMS and extensive NMR spectroscopic techniques. The absolute configurations of their sugars were determined by GC analysis. The pharmacological assay showed that compounds 2, 3, and 9-11 displayed remarkable hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage at the concentration of 10µM (Bicyclol as positive contrast).

An Approach for Determining the Absolute Configuration of C-2 in 2-Oxygenated Phenylethanoid Glycosides by (1)H NMR Spectroscopy.

The absolute configurations of 2-oxygenated phenylethanoid glycosides were conveniently determined by (1)H NMR spectroscopy. A comparison of the chemical shift differences (Δδ) of the diastereotopic methylene protons (H-1) demonstrate that a large chemical shift difference corresponds to an R configuration and a small chemical shift difference indicates S for the 2-alkoxy form. However, the situation is contrary to that of the 2-hydroxy form. Furthermore, the mechanism underlying this result is discussed based on the visualized conformations of such compounds.

Protective effects of Forsythia suspense extract with antioxidant and anti-inflammatory properties in a model of rotenone induced neurotoxicity.

The present study investigated the neuroprotective effects of Forsythia suspense extract in a rotenone-induced neurotoxic model. FS8, one of the herbal extracts, markedly protected PC12 cells against rotenone toxicity and was selected for the in vivo study. Gavage administration of FS8 (50 and 200mg/kg, but not 10mg/kg) for 25 days significantly improved the behavior function, decreased the loss of dopaminergic neurons in substantia nigra (SN), and maintained the level of dopamine in striatum after unilateral infusion of rotenone in SN. Wherein, the protective effects of FS8 at the dose of 200mg/kg were better than selegiline. Further study indicated the excellent antioxidant activity of FS8 on the 5th and 21st days after intranigral injection of rotenone. Moreover, FS8 could inhibit microglia activity and accumulation in SN, and obviously decreased the expression of pro-inflammatory molecules (IL-6, TNF-α, iNOS and COX-2), which indicated the anti-inflammatory effects of FS8. In the PI3K/Akt/NF-κB and MAPK pathways, FS8 significantly down-regulated the protein expression of p-PI3K, p-Akt, p-IκB, p-P65, cleaved Caspase 8, p-p38 and p-JNK but not p-mTOR, cleaved Caspase 3 and p-ERK. Therefore, FS8 protected dopamine neurons against rotenone toxicity via antioxidant and anti-inflammatory effects, which suggested the promising application of FS8 in the prevention and treatment of Parkinson disease.