Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2 ± 1.6 μM. Enzyme-linked immunosorbent assay and fluorescence quantitative polymerase chain reaction analyses indicated that watsonianone A markedly reduced both mRNA and protein levels of tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, watsonianone A inhibited nuclear factor κB (NF-κB) activation by suppressing IκBα phosphorylation. Further analysis revealed that watsonianone A activated the thioredoxin system and decreased intracellular reactive oxygen species (ROS) levels, which are closely associated with NF-κB activation in RSV-infected cells. These results reveal that watsonianone A can attenuate RSV-induced inflammation via the suppression of ROS-sensitive inflammatory signaling.Keywords: inflammation; respiratory syncytial virus; Rhodomyrtus tomentosa; ROS; watsonianone A;

Four novel matrine-based alkaloids (1–4) were isolated from the seeds of Sophora alopecuroides. Compounds 1 and 2 possess unprecedented 6/6/6/4 and 6/5/6/6 ring systems, respectively, while 3 and 4 are a pair of stereoisomeric matrine–acetophenone alkaloids with an unusual skeleton. Their structures were elucidated by means of spectroscopic methods and single-crystal X-ray diffraction. Hypothetical biogenetic pathways for 1–4 are proposed, and their antiviral activities are also discussed.

•Seven previously unknown sesquiterpene lactones, elephanpene A-G, along with ten known ones were isolated from Elephantopus mollis.•Anti-inflammatory activities of the isolates were evaluated.•All tested compounds exhibited anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 59.97 ± 1.53 μM.Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.7 cells, and all tested compounds exhibited potent anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 14.34 ± 1.61 μM, except that compound tomenphantopin C exhibited moderate anti-inflammatory activity with IC50 values of 59.97 ± 1.53 μM.Seven sesquiterpene lactones and ten known ones were isolated from herbs of Elephantopus mollis. Selected compounds were evaluated for their anti-inflammatory activities by using the Griess assay.Download high-res image (223KB)Download full-size image

Nine new labdane diterpenoids (1–9) were isolated from the aerial parts of Croton laui, along with eight known analogues (10–17). Their structures were identified on the basis of the spectral data (IR, UV, HRESIMS, 1D and 2D NMR), and the structure of 8 was confirmed by single crystal X-ray diffraction analyses. In addition, compounds 1, 4, 7, 8, and 14 showed weak anti-inflammatory activities in LPS-stimulated RAW 264.7 cells.

Six unusual matrine-type alkaloid dimers, flavesines A–F (1–6, respectively), together with three proposed biosynthetic intermediates (7–9) were isolated from the roots of Sophora flavescens. Compounds 1–5 were the first natural matrine-type alkaloid dimers, and compound 6 represented an unprecedented dimerization pattern constructed by matrine and (−)-cytisine. Their structures were elucidated by NMR, MS, single-crystal X-ray diffraction, and a chemical method. The hypothetical biogenetic pathways of 1–6 were also proposed. Compounds 1–9 exhibited inhibitory activities against hepatitis B virus.

Three novel sesquiterpenoid-based meroterpenoids, drychampones A–C (1–3, respectively), were isolated from Dryopteris championii. Compounds 1 and 3 possessed a novel carbon skeleton which was constructed by an 11/6/6 ring system coupled with a pyronone moiety, and 1–3 were three racemates. Their structures and absolute configurations were elucidated by NMR, MS, and computational methods. The hypothetical biosynthetic pathways of these meroterpenoids and their antibacterial activities were also discussed.

Seven new phloroglucinol derivatives (1–7) were isolated from the fruit tree Syzygium jambos together with four known triterpenoids (8–11) and two known flavones (12 and 13). According to the spectroscopic analyses (infrared, electrospray ionization mass spectrometry (ESIMS), high-resolution ESIMS, 1D and 2D nuclear magnetic resonance), the structures of compounds 1–7 were elucidated as jambone A (1), jambone B (2), jambone C (3), jambone D (4), jambone E (5), jambone F (6), and jambone G (7). All the isolates were determined for their cytotoxic activities on melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and compounds 10 and 11 showed potent activities. Moreover, compounds 1, 2, 4–7, 12, and 13 exhibited weak antioxidant activities under ferric-reducing antioxidant power and 2,2-diphenyl-1-picryhydrazyl radical-scavenging assays.

Human respiratory syncytial virus (RSV) is a common pathogen that causes pneumonia and bronchiolitis in infants and young children. Our previous study showed that tangeretin from Citrus reticulate possessed potent in vitro anti-RSV effects comparable to that of ribavirin. Therefore, in this study, we investigated the in vivo anti-RSV activity of tangeretin in 3-week-old male BALB/c mice. A plaque reduction assay and fluorescence quantitative polymerase chain reaction (FQ-PCR) showed that tangeretin inhibited RSV replication in the lung of mice. Moreover, a luminex assay indicated tangeretin relieved RSV-induced lung inflammation by attenuating interleukin (IL)-1β secretion. Possible anti-inflammatory mechanisms of tangeretin were preliminarily explored using a RSV-infected macrophage model. A FQ-PCR, enzyme-linked immunosorbent assay (ELISA), and luciferase assay revealed that tangeretin inhibited RSV-induced inflammation by suppressing nuclear factor-κB (NF-κB) activation. This study demonstrates that tangeretin inhibited RSV replication and RSV-induced lung inflammation in vivo and may be useful in preventing and treating RSV infections and inflammation.

•The chemical constituents of Schima superba were investigated.•Eight new oleanane-type triterpenoid saponins, along with eight known triterpenoid saponins, were isolated and identified.•The cytotoxicity of all compounds against B16 melanoma cells was evaluated.Eight new oleanane-type triterpenoid saponins, schisusaponins A-H, along with eight known triterpenoid saponins, were isolated from the root bark of Schima superb (Theaceae). Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical methods. The cytotoxicity of the new compounds against B16 melanoma cells was assessed. Among the isolated new saponins, schisusaponins C and E showed more potent effects (with IC50 values of 10.08 and 10.89 μM) than vinblastine (with an IC50 value of 19.48 μM).

A pair of new enantiomeric stilbene dimers, (+)- and (−)-cajanusine [(+)-1 and (−)-1], with a unique coupling pattern were isolated from the leaves of Cajanus cajan. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic and single-crystal X-ray diffraction analyses, as well as CD calculations. The plausible biogenetic pathway of 1 was also proposed. Additionally, (±)-1, (+)-1, and (−)-1 exhibited inhibitory activities on the growth of human hepatocellular carcinoma cells.

•Six new and five known phenolic compounds were isolated from Origanum vulgare.•Twenty-one phenolic compounds from Origanum vulgare were evaluated for their in vitro antioxidant and antiviral activities.•Twelve phenolic compounds were found to have potent antioxidant activity.•Some phenolic compounds were found to have weak antiviral activity.In the present study, six new phenolic compounds (1–6) along with five known ones were isolated from the ethanol extract of the whole plants of Origanum vulgare. The structures of the new compounds were identified on the basis of extensive spectroscopic analyses (UV, IR, NMR, and HRESIMS) and acid hydrolysis. Twenty-one phenolic compounds isolated from O. vulgare in our previous and present studies were evaluated for their in vitro antioxidant activity using 2,2-diphenyl-1-picryhydrazyl (DPPH) radical-scavenging and ferric-reducing antioxidant power (FRAP) assays; twelve of them including two new compounds exhibited significant antioxidant activity comparable to that of ascorbic acid. In addition, the antiviral effects against respiratory syncytial virus (RSV), Coxsackie virus B3 (CVB3) and herpes simplex virus type 1 (HSV-1) were tested by cytopathic effect (CPE) reduction assay.

The present study found that the supercritical fluid extract of “Guangchenpi” possessed in vitro antiviral activity against respiratory syncytial virus (RSV). Bioassay-guided isolation and identification of this extract led to obtain five active polymethoxylated flavones (1–5). Cytopathic effect (CPE) reduction assay exhibited that tangeretin (2) and nobiletin (3), two major polymethoxylated flavones in the extract, possessed better anti-RSV effect comparable to the positive control ribavirin. Plaque reduction assay revealed that tangeretin dose-dependently inhibited RSV-induced plaque formation on the HEp-2 cells. This polymethoxylated flavone mainly affected the intracellular replication of RSV, and it also could inhibit RSV entry into the HEp-2 cells. Further investigations with quantitative real-time PCR and confocal and Western blot assays indicated that tangeretin downregulated the expression of RSV phosphoprotein (P protein). Results suggest the potential application of the supercritical fluid extract of “Guangchenpi” and tangeretin in the treatment and the prevention of RSV infection.

•Chemical constituents of aerial parts of Schefflera kwangsiensis were investigated.•Eight new oleanane-type triterpenoid saponins (1–8) were isolated.•The structures of the new compounds were elucidated by spectroscopic methods and acid hydrolysis.•The saccharide chains linked to C-28 of oleanolic acid in compounds 1–5 were selectively acetylated.Eight new oleanane-type triterpenoid saponins, named schefflesides A–H (1–8), were isolated from the aerial parts of Schefflera kwangsiensis. The structures of these new compounds were established on the basis of hydrolysis and spectroscopic evidence, including 1D- and 2D-NMR (HSQC, HMBC, ROESY and TOCSY) and HR-MS analyses.Graphical abstract

Phytochemical investigation of the rhizomes of Paris polyphylla var. yunnanensis resulted in the isolation of six new oleanane-type triterpenoid saponins, paritrisides A–F (1–6), along with nine known triterpenoid saponins (7–15). The structures of the new compounds were elucidated on the basis of spectroscopic analysis and acid hydrolysis. All the triterpenoid saponins are obtained for the first time from the genus Paris. The isolated compounds were assayed for their cytotoxic activities against human nasopharyngeal carcinoma epithelial (CNE) cells, and compounds 7, 8, and 10 exhibited inhibitory effects on CNE cell growth with IC50 values of 16.53, 16.77, and 12.69 μm, respectively.Graphical abstractHighlights► Six new triterpenoid saponins were isolated from Paris polyphylla var. yunnanensis. ► The triterpenoid saponins are reported firstly from the genus Paris. ► Known compounds 7, 8, and 10 exhibited inhibition against CNE cells.

•Ten eudesmane-type sesquiterpenes and twelve known ones were isolated from Laggera alata.•The structures of two compounds were confirmed by X-ray diffraction analysis.•All compounds were evaluated for cytotoxic activities on six cancer cell lines.Ten eudesmane-type sesquiterpene derivatives (1–10), including six cuauhtemone derivatives (1–6), one di-norsesquiterpene (3-oxo-di-nor-eudesma-4-en-11-oic acid, 7), and three eudesmane glycosides (alatoside F–H, 8–10) were isolated from the whole plants of Laggera alata together with 12 known compounds. Their structures were elucidated on the basis of extensive spectroscopic analysis, acid hydrolysis, and compounds 1 and 7 were studied by single-crystal X-ray diffraction analysis. The absolute configuration of 1 was determined by the application of the modified Mosher’s method. All of the isolated eudesmane-type sesquiterpenes were evaluated for their cytotoxic activities on six human cancer cell lines, but all of the compounds were inactive on the tested cell lines in the concentration of 100 μg/mL.Ten eudesmane-type sesquiterpene derivatives and twelve known ones were isolated from Laggera alata. All the isolated compounds were evaluated for their cytotoxic activities on six human cancer cell lines.

Seven new clerodane diterpenoids (1–7) were isolated from roots of Croton crassifolius, along with six known compounds. The structures were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the structures of 1, 3, 4, and 7 were confirmed by single-crystal X-ray diffraction analyses. Compounds 1–13 were evaluated for in vitro antiviral activity against herpes simplex virus type 1 using the cytopathic effect reduction assay.

Eleven steroidal saponins, along with seven known steroidal saponins, were isolated from rhizomes of Paris polyphylla var. yunnanensis. Their chemical structures were elucidated on the basis of spectroscopic analyses and acid hydrolysis. Two of these compounds contained a spirostanol saponin aglycone, hitherto unknown in Nature. The isolated compounds were tested for their cytotoxic effects on human nasopharyngeal carcinoma epithelial (CNE) cells, and seven compounds displayed more potent inhibitory effects than cisplatin (the positive control). One compound with diosgenin and tetrasaccharide moieties possessed the strongest inhibitory effect on CNE cells through the induction of apoptosis and cell cycle arrest.Graphical abstractEighteen steroidal saponins were isolated from Paris polyphylla var. yunnanensis, seven of which were previously known. Two of these compounds (shown below) contain the hitherto unknown natural spirostanol saponin aglycone. All the compounds were tested for their cytotoxic effect on human nasopharyngeal carcinoma cells.Highlights► The report of (3β,5α,6β,25R)-spirostane-3,5,6-triol as a spirostanol saponin aglycone. ► Isolation of the aglycone (3β,25R)-3-hydroxyspirost-5-en-7-one from the genus Paris. ► A number of compounds showed more potent inhibitory effects on CNE cells than cisplatin.

Pseudoguaianolide sesquiterpene lactones minimolides A (1), B (2), C (3) and D (4) and two guaianolide sesquiterpene lactones minimolides E (5) and F (6), along with seven known ones (7–13), were isolated from the supercritical fluid extract of Centipeda minima. The structures of these compounds were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D-NMR and 2D-NMR), and the complete structure and stereochemistry of 1 was further confirmed by X-ray diffraction analysis. Compounds 1, 5–8,11 and 13 displayed inhibitory activity against human nasopharyngeal cancer cells (CNE) with IC50 values ranging from 1.1 to 20.3 μM. Compound 13 containing both α-methylene-γ-lactone and α, β-unsaturated cyclopentenone moieties exhibited even stronger inhibitory activity than that of cisplatin (positive control) through cell cycle arrest at G2/M phase. Isolation of six sesquiterpene lactones from Centipeda minima highlighted the potential of supercritical fluid extraction for enrichment of minor constituents for phytochemical study.Graphical abstractSesquiterpene lactones (1–6) with significant inhibitory activity against human nasopharyngeal cancer cells were isolated from the supercritical fluid extract of Centipeda minima.Highlights► Supercritical fluid extraction was used to enrich low polar constituents. ► Six sesquiterpene lactones (1–6) along with seven known ones were isolated. ► Some compounds showed inhibitory activity against human nasopharyngeal cancer cells. ► Structure-relationships are discussed.

A new pyromeconic acid derivative, pyromeconic acid-3-O-β-d-glucopyranoside-3′-(O-β-d-glucopyranoside)-6′-(O-4″-hydroxybenzoate) (1), along with two known ones, were isolated from the whole plants of Conyza canadensis. Their structures were elucidated based on the analysis of their spectroscopic data. The in vitro antibacterial testing results showed that all of these three compounds were inactive towards two bacterial strains, Escherichia coli and Staphyloccocus aureus.

BackgroundWedelia chinensis is a traditional medicinal herb used in Asia and it has been reported to possess various bioactivities including anti-inflammatory and anticancer effects. However, its anti-angiogenic activity has never been reported.PurposeTo determine the most potent anti-angiogenic component in W. chinensis and its molecular mechanism of action.Study designInitially, the active fraction of the plant was studied. Then, we determined the active components of the fraction and explored the mechanism of the most active compound.MethodsThe ethanol extract of W. chinensis and its four fractions with different polarities were evaluated for their anti-angiogenic activity in the Zebrafish model using quantitative endogenous alkaline phosphatase (EAP) assay. The molecular mechanism of the most active compound from the active fraction was studied using the real-time polymerase chain reaction (PCR) assay on Zebrafish embryos. The inhibitory effect of the most active compound on the proliferation, invasion and tube formation steps of angiogenesis was evaluated using the vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs) model, and the influences of the active compound on tyrosine phosphorylation of VEGF receptor (VEGFR-2) and its downstream signal pathway were evaluated by western blotting assay. Moreover, its anti-angiogenic effect was further evaluated by the VEGF-induced sprouts formation on aortic ring assay and the VEGF-induced vessel formation of mice on matrigel plug assay, respectively.ResultsPetroleum ether (PE) fraction of the plant displayed potent anti-angiogenic activity. Twelve kaurane diterpenoids (1-12) isolated from this fraction showed quite different effects. Compounds 9-12 could dose-dependently inhibit vessel formation in the Zebrafish embryos while the others showed little inhibitory effect. Among the active diterpenoids, compound 10, 3α-cinnamoyloxy-9ß-hydroxy-ent-kaura-16-en-19-oic acid (CHKA), possessed the strongest effect, and it affected multiple molecular targets related to angiogenesis including VEGF and angiopoietin in Zerbrafish. Moreover, CHKA significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, invasion, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways in HUVECs. CHKA also obviously inhibited sprouts formation of aortic ring, and block vessel formation in mice.ConclusionOur findings demonstrate that kaurane diterpenoids is one of anti-angiogenic components in W. chinensis, and CHKA may become a promising candidate for the development of anti-angiogenic agent.Download high-res image (195KB)Download full-size image