Symplosaponins A-D: New acylated oleanane-type triterpene saponins from Symplocos cochinchinensis and their hepatoprotective effect.

Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5-9), 2-methoxy-4-prop-1-enylphenyl-1-O-ß-D-apiofuranosyl-(1 → 6)-ß-D-glucopyranoside (5), and 1-[O-ß-d-xylopyranosyl-(1 → 6)-O-ß-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (-)-secoisolariciresinol-O-ß-D-glucopyranoside (9). The structures of these compounds were elucidated through spectroscopic methods, comparison with existing data, and chemical methods. Furthermore, all compounds were assessed for their impact on hepatocellular viability using the Resazurin reduction assay. These investigations aimed to explore the potential hepatoprotective properties of isolated compounds. As a result, 1-[O-ß-d-xylopyranosyl-(1 → 6)-O-ß-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6) and (-)-secoisolariciresinol-O-ß-D-glucopyranoside (9) demonstrated statistically significant hepatoprotective activity in a concentration-dependent manner.

Four Undescribed Stilbenoid Derivatives from the Aerial Parts of Dendrobium officinale with their α-Glucosidase and α-Amylase Inhibitory Activity.

In this study, four undescribed bibenzyl derivatives (1-4), together with seven known compounds (5-11) were isolated from the aerial parts of Dendrobium officinale. Their chemical structures were determined to be (7'S,8'S) -9''-acetyldendrocandin U (1), (7'S,8'S) -4'-methoxydendrocandin T (2), (7'R,8'S) -dendrocandin B (3), (1S,2R) -5'''-methoxydendrofindlaphenol C (4) by analyzing of the spectroscopic data including HR-ESI-MS, 1D-, and 2D-NMR spectra. The absolute configurations of compounds 1-4 were determined by the electronic circular dichroism (ECD) spectra. Compounds 1-3, 5, 10 and 11 inhibited α-glucosidase with the IC50 values ranging from 56.3 to 165.3 µM, compounds 1-3, 5, 7-10 inhibited α-amylase with the IC50 values ranging from 65.2 to 177.6 µM.

Chryroxosides A-E: five new triterpene saponins from the leaves of Chrysophyllum roxburghii G.Don. and their cytotoxic activity.

Five undescribed oleanane triterpene glycosides named chryroxosides A-D (1-5), together with five known compounds (6-10) were isolated from the leaves of Chrysophyllum roxburghii G.Don. Their chemical structures were elucidated by extensive spectroscopic data analyses including IR, HR-ESI-MS, 1D and 2D NMR). Compounds 1, 3, and 5 showed cytotoxic effects against KB, HepG2, HL60, P388, HT29, and MCF7 cell lines with the IC50 values ranging from 14.40 to 52.63 µM compared to the positive control compound (ellipticine) with the IC50 values ranging from 1.34 to 1.99 µM.

Antimicrobial and Cytotoxic Secondary Metabolites from a Marine-Derived Fungus Penicillium Citrinum VM6.

Investigation of an antimicrobial and cytotoxic ethyl acetate extract prepared from solid fermentation of the marine-derived fungus Penicillium citrinum VM6 led to the isolation of eight metabolites (1-8), including one citrinin dimer dicitrinone F (1). Of these, compound 7 was isolated for the first time from the Penicillium genus and compound 1 with carbon-bridged C-7/C-7' linkage is rarely reported. All compounds (1-8) exhibited selective antimicrobial activity against the tested Gram-positive bacteria and Candida albicans with MICs of 32-256 µg/mL. Compounds 1 and 8 exhibited cytotoxicity against all tested cell lines A549, MCF7, MDA-MB-231, Hela, and AGS with IC50 values of 6.7 ± 0.2 to 29.6 ± 2.2 µg/mL, whereas compound 5 had selective cytotoxicity against the MCF7 cell lines with IC50 of 98.1 ± 7.8 µg/mL.

Antimicrobial Activity of Depsidones and Macrocyclic Peptides Isolated from Marine Sponge-Derived Fungus Aspergillus nidulans M256.

Chemical study on marine sponge-derivated fungus Aspergillus nidulans resulted in the isolation of seven depsidones (1-7) and two macrocyclic peptides (8 and 9). Their chemical structures were elucidated by extensive analyses of HRESIMS and NMR spectral data, as well as comparison with the literature. Compound 1 was an undescribed depsidone. All compounds exhibited significant antimicrobial activity (MICs: 2-128 µg/mL) towards at least one of seven microbial strains, including Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, and Candida albicans. Of these, chlorinated depsidones (1-3, and 5) displayed potential antimicrobial activity. Nidulin (2) possessed good activity against tested strains except for S. enterica with MIC values in range of 2-16 µg/mL. Interestingly, undescribed depsidone 1 was selectively bioactive on the Gram-positive bacteria (MICs: 2-4 µg/mL) and yeast (MIC: 8 µg/mL) but inactivity on the Gram-negative bacteria (MICs: >256 µg/mL). Macrocyclic peptides, 8 and 9, displayed modest activity against E. faecalis strain with MIC values of 32 and 128 µg/mL, respectively.

Garcimckeans A-C, three new xanthones from the stems of Garcinia mckeaniana, and their cytotoxic activity.

Three new xanthones, garcimckeans A-C (1-3) were isolated from the methanol extract of the stems of Garcinia mckeaniana (Clusiaceae). Their structures were established by extensive spectroscopic analysis (HR-ESI-MS and 1 D and 2 D NMR) and by comparison of the spectral data with those reported in the literature. Compounds 1-3 displayed weak cytotoxic activity toward KB, Lu, HepG2, and MCF7 cell lines using the MTT assay with IC50 values ranging from 71.03 ± 2.93 to 90.40 ± 7.13 µM compared to that of the positive control compound, ellipticine (IC50: 1.22 ± 0.10 ∼ 2.44 ± 0.2 µM).

A new flavonoid from the leaves of Garcinia mckeaniana Craib and α-glucosidase and acetylcholinesterase inhibitory activities.

From the ethyl acetate extract (EtOAc) of the Vietnamese Garcinia mckeaniana leaves, a new flavone 8-C-glycoside 2'',6''-di-O-acetylvitexin (1), together with six known analogs 2-7 were isolated. Their structures were determined by spectral methods and compared with literature data. In α-glucosidase inhibitory assay, the EtOAc extract and its flavone and biflavone derivatives possessed the significant IC50 range of 9.17-97.53 µM, as compared with that of the positive control acarbose (249 µM). Flavones and biflavones showed are better than flavone glycosides in both α-glucosidase and acetylcholinesterase inhibitory activities[Formula: see text].

Anti-Inflammatory Properties of Longifuran A, a New Benzofuran from the Stems of Amomum longiligulare.

In this study, the following compounds were isolated from the dichloromethane fraction of the stems of Amomum longiligulare and then characterized: a new benzofuran, namely, longifuran A (1); five other phenolic compounds, namely, 4-methoxycinnamic acid (2), 2,5-dimethoxyphenol (3), eudesmic acid (4), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (5), and 4,4'-dihydroxychalcone (6); and two triterpenoids, namely, 24-methylcycloartan-3ß-ol (7) and 24-methylencycloartan-3ß-ol (8). They were evaluated in terms of their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophages. Results indicated that 1 and 5 exhibited promising inhibitory activities against NO generation with IC50 of 10.47±1.02 µM and 8.51±1.14 µM, respectively. Enzymatic assays demonstrated that they remarkably suppressed the secretion of two pro-inflammatory cytokines (i. e., IL-6 and TNF-α). They also dose-dependently inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2, two important enzymes modulating inflammation. Therefore, 1 and 5 could be targets for the development of new anti-inflammatory therapeutics.

Cytotoxic and α-Glucosidase Inhibitory Xanthones from Garcinia mckeaniana Leaves and Molecular Docking Study.

A new racemic xanthone, garmckeanin A (1), and eight known analogs 2-9 were isolated from the ethyl acetate (AcOEt) extract of the Vietnamese Garcinia mckeaniana leaves. Their structures were determined by MS and NMR spectral analyses and compared with the literature. The AcOEt extract showed good cytotoxicity against cancer cell lines KB, Lu, Hep-G2 and MCF7, with IC50 values of 5.40-8.76 µg/mL, and it also possessed α-glucosidase inhibitory activity, with an IC50 value of 9.17 µg/mL. Garmckeanin A (1) exhibited inhibition of all cancer cell lines, with an IC50 value of 7.3-0.9 µM. Allanxanthone C (5) successfully controlled KB growth, with an IC50 value of 0.54 µM, higher than that of the positive control, ellipticine (IC50 1.22 µM). Norathyriol (8) was a promising α-glucosidase inhibitor, with an IC50 value of 0.07 µM, much higher than that of the positive control, acarbose (IC50 161.0 µM). The interactions of the potential α-glucosidase inhibitors with the C- and N-terminal domains of human intestinal α-glucosidase were also investigated by molecular docking study. The results indicated that bannaxanthone D (2), garcinone E (4), bannaxanthone E (6), and norathyriol (8) exhibit higher binding affinity to the C-terminal than to the N-terminal domain through essential residues in the active sites. In particular, compound 8 could be assumed to be the most potent mixed inhibitor.

Prenylated flavonoids and other constituents from Macaranga indica.

Four new prenylated flavonoids, macarindicins I-IV (1-4) together with ten known compounds, broussoflavonol F (5), vedelianin (6), schweinfurthin E (7), vitexin (8), 2″-rhamnosyl vitexin (9), isovitexin (10), (6R,7E,9R)-9-hydroxy-megastigman-4,7-dien-3-one-9-O-ß-D-glucopyranoside (11), 6S,9R)-roseoside (12), (6S,9S)-roseoside (13), and bridelionoside B (14) were isolated from the leaves of Macaranga indica. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-, 2D-NMR, and MS data. All the isolated compounds were evaluated for their cytotoxic activities against four human cancer cell lines including KB, MCF-7, HepG-2, and LU. As a result, compound 6 significantly exhibited cytotoxic activity against all tested human cancer cell lines with IC50 values ranging from 4.7 to 11.0 µM. Compounds 2, 5, and 7 showed moderate cytotoxic activity with IC50 values ranging from 7.0 to 38.7 µM.

Essential Oils of Lemongrass (Cymbopogon citratus Stapf) Induces Apoptosis and Cell Cycle Arrest in A549 Lung Cancer Cells.

Essential oils were extracted from the culm and leaf of Cymbopogon citratus collected from different regions of Vietnam and analyzed using GC/MS. The results showed that citral is the major component accounting for 61.20%-76.46% of the essential oils. The citral content was higher in the essential oil obtained from the leaf than in that from the culm of lemongrass in all regions. In particular, camphene, valerianol, and epi-α-muurolol can be used to differentiate essential oils originating from leaves versus culms. The cytotoxic effects of the essential oils on various lung cancer cell lines were evaluated in the present study. All essential oils exhibited cytotoxicity in the tested cells. The Ha Loc leaf essential oil (HLL) exhibited the most potent effects on A549 and H1975 cells, with IC50 values of 1.73 ± 0.37 and 4.01 ± 0.30 µg/mL, respectively. The Hy Cuong leaf essential oil (HCL) showed the strongest effect on H1299 cells, with an IC50 value of 2.45 ± 0.21 µg/mL. The Kim Duc culm (KDC) essential oil exerted the strongest cytotoxic effects against H1650 cells, with an IC50 value of 4.86 ± 0.29 µg/mL. The HLL induced apoptosis and cycle arrest in A549 cells according to flow cytometric analysis and fluorescent nuclear staining assays. The western blot analysis indicated that HLL induced the apoptotic effect by altering the regulating proteins of the apoptosis process such as caspase-3, Bcl-2, and Bax. The data strongly suggested that the intrinsic pathway may play an important role in the apoptotic effects of HLL.

Ethanol extract of Polyscias fruticosa leaves suppresses RANKL-mediated osteoclastogenesis in vitro and LPS-induced bone loss in vivo.

BACKGROUND: Many bone-related diseases such as osteoporosis and rheumatoid arthritis are commonly associated with the excessive activity of osteoclasts. Polyscias fruticosa has been used as traditional medicine for the treatment of ischemia and inflammation and also eaten as a salad. However, its effect on the bone related diseases has not been investigated yet. PURPOSE: This study aimed to investigate the effect of ethanol extract of P. fruticosa on RANKL-induced osteoclastogenesis in vitro and LPS-induced bone loss in mouse, and evaluate anti-osteoclastogenic activities of its major constituents. METHODS: BMMs or RAW264.7 cells were treated with ethanol extract from P. fruticose leaves (EEPL), followed by an evaluation of cell viability, RANKL-induced osteoclast differentiation, actin-ring formation, and resorption pits activity. Effects of EEPL on RANKL-induced phosphorylation of MAPKs were evaluated by Western blotting. The expression levels of NFATc1 and c-Fos were evaluated by Western blotting or immunofluorescence assay. The expression levels of osteoclast-specific marker genes were evaluated by Western blotting and reverse transcription-qPCR analysis. A LPS-induced murine bone loss model was used to evaluate the protective effect of EEPL on inflammation-induced bone loss. HPLC analysis was performed to identify the major constituents of EEPL. RESULTS: EEPL significantly inhibited RANKL-induced osteoclast differentiation by decreasing the number of osteoclasts, osteoclast actin-ring formation, and bone resorption. EEPL suppressed RANKL-induced phosphorylation of p38 and JNK MAPKs, as well as the expression of c-Fos and NFATc1. EEPL decreased the expression levels of osteoclast marker genes, including MMP-9, TRAP and CtsK. Mice treated with EEPL significantly protected the mice from LPS-induced osteoclast formation and bone destruction as indicated by micro-CT and histological analysis of femurs. We also identified 3-O-[ß-d-glucopyranosyl-(1→4)-ß-d-glucuronopyranosyl] oleanolic acid 28-O-ß-d-glucopyranosyl ester (1) and quercitrin (3) as the active constituents in EEPL for inhibiting RANKL-induced osteoclast differentiation. CONCLUSION: The results showed that EEPL exerted anti-osteoclastogenic activity in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function, and suggested that EEPL could have beneficial applications for preventing or inhibiting osteoclast-mediated bone diseases.

Ganomycin I from Ganoderma lucidum attenuates RANKL-mediated osteoclastogenesis by inhibiting MAPKs and NFATc1.

BACKGROUND: Many bone-related diseases such as osteoporosis and rheumatoid arthritis are commonly associated with excessive activity of the osteoclast. Ganomycin I (GMI), a meroterpenoid isolated from Vietnamese mushroom Ganoderma lucidum, possesses a variety of beneficial effects on human health. However, its impact and underlying mechanism on osteoclastogenesis remain unclear. In the present study, we investigated the effect of GMI on RANKL-induced osteoclast formation in mouse BMMs and RAW264.7 cells. METHODS: BMMs or RAW264.7 cells were treated with GMI followed by an evaluation of cell viability, RANKL-induced osteoclast differentiation, actin-ring formation, and resorption pits activity. Effects of GMI on RANKL-induced phosphorylation of MAPKs as well as the expression levels of NFATc1 and c-Fos were evaluated by Western blot analysis. Expression levels of osteoclast marker genes were evaluated by Western blot analysis and reverse transcription-qPCR. RESULTS: GMI significantly inhibited RANKL-induced osteoclast differentiation by decreasing the number of osteoclasts, osteoclast actin-ring formation, and bone resorption in a dose-dependent manner without affecting cell viability. At molecular level, GMI inhibited the RANKL-induced phosphorylation of ERK, JNK, and p38 MAPKs, as well as the expression levels of c-Fos and NFATc1, which are known to be crucial transcription factors for osteoclast formation. In addition, GMI decreased expression levels of osteoclastogenesis specific marker genes including c-Src, CtsK, TRAP, MMP-9, OSCAR, and DC-STAMP in RANKL-stimulated BMMs. CONCLUSION: Our findings suggest that GMI can attenuate osteoclast formation by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and the anti-osteoclastogenic activity of GMI may extend our understanding of molecular mechanisms underlying biological activities and pharmacological use of G. lucidum as a traditional anti-osteoporotic medicine.

Degalactotigonin, a Steroidal Glycoside from Solanum nigrum, Induces Apoptosis and Cell Cycle Arrest via Inhibiting the EGFR Signaling Pathways in Pancreatic Cancer Cells.

Degalactotigonin (1) and three other steroidal compounds solasodine (2), O-acetyl solasodine (3), and soladulcoside A (4) were isolated from the methanolic extract of Solanum nigrum, and their chemical structures were elucidated by spectroscopic analyses. The isolated compounds were evaluated for cytotoxic activity against human pancreatic cancer cell lines (PANC1 and MIA-PaCa2) and lung cancer cell lines (A549, NCI-H1975, and NCI-H1299). Only degalactotigonin (1) showed potent cytotoxicity against these cancer cell lines. Compound 1 induced apoptosis in PANC1 and A549 cells. Further study on its mechanism of action in PANC1 cells demonstrated that 1 significantly inhibited EGF-induced proliferation and migration in a concentration-dependent manner. Treatment of PANC1 cells with degalactotigonin induced cell cycle arrest at G0/G1 phase. Compound 1 induced downregulation of cyclin D1 and upregulation of p21 in a time- and concentration-dependent manner and inhibited EGF-induced phosphorylation of EGFR, as well as activation of EGFR downstream signaling molecules such as Akt and ERK.

Two new sesquiterpenes from the fruits of Fissistigma villosissimum.

Two new sesquiterpenes, namely fissistinone (1) and fissistinol (2), along with ten known compounds (3-12), were isolated from the fruits of Fissistigma villosissimum. Their structures were elucidated on the basis of spectral data analysis, including one-dimensional (1D), two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS). Compounds 1-8 were evaluated for their cytotoxic activities against KB cell line; however, all these compounds did not show cytotoxic activity.