Six New Polyoxygenated Xanthones from Garcinia cowa and Their Neuroprotective Effects on Glutamate-Mediated Hippocampal Neuronal HT22 Cell Death.

Six new polyoxygenated xanthones, garcicowanones F-H (1-3), norcowanol A-B (4-5), and garcinone F (6) along with twelve known compounds 7-18 were obtained from the latex of Garcinia cowa Roxb. ex Choisy. All new compounds have a 1,3,7-trioxygenated or 1,3,6,7-tetraoxygenated xanthone nucleus and differ from majority of xanthones from G. cowa by hydrated side chains. Compounds 1, 7, 8 and 18 exhibited significant neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death. In particular, compound 1 exhibited the most potent neuroprotective effect with >80 % cell viability in the concentration range of 2.9-115 µM. Further studies on compound 1 showed that it decreased cellular Ca2+ influx and inhibits cellular reactive oxygen species generation in HT22 cells. A Western blot analysis showed that MAPK phosphorylation, Bax, and AIF translocation dramatically increased upon treatment with 5 mM glutamate and decreased upon a co-treatment with compound 1.

Chemical Constituents of Eupatorium japonicum and Anti-Inflammatory, Cytotoxic, and Apoptotic Activities of Eupatoriopicrin on Cancer Stem Cells.

Eupatorium japonicum Thunb. of the plant family Asteraceae is a popular traditional herb in Vietnam. However, its chemical constituents as well as bioactive principles have not been investigated yet. We investigated the phytochemistry of E. japonicum in Vietnam and isolated seventeen compounds (1-17) including phytosterols, terpenoids, phenolic acids, flavonoids, fatty alcohols, and fatty acids. They were structurally determined by MS and NMR analysis. Except for compounds 6 and 12, all the other compounds were identified for the first time from E. japonicum. Since many sesquiterpene lactones with α-methylene γ-lactone ring are reported as anti-inflammatory and anticancer agents, eupatoriopicrin (10), 1-hydroxy-8-(4,5-dihydroxytigloyloxy)eudesma-4(15),11(13)-dien-6,12-olide (11) were selected among the isolates for biological assays. Compound 10 was identified as the main bioactive sesquiterpene lactone of E. japonicum showing its potent anti-inflammatory and cytotoxic activity through inhibiting NO production and the growth of HepG2 and MCF-7 human cancer cell lines. For the first time, eupatoriopicrin (10) was demonstrated to strongly inhibit NTERA-2 human cancer stem cell (CSC) line in vitro. It is noticeable that the cytotoxicity of eupatoriopicrin against NTERA-2 cells is mediated by its apoptosis-inducing capability of 10 as demonstrated by the results of Hoechst 33342 staining, flow cytometry apoptosis analysis, and caspase-3 activity assays. The biological activities of the main bioactive constituents 1-7, 10, 12, and 15 supported the reported anti-inflammatory and anticancer properties of extracts from E. japonicum.

Methylated Flavonols from Amomum koenigii J.F.Gmel. and Their Antimicrobial and Antioxidant Activities.

Methylated flavonols form a special group with modulating biological activities in comparison with kaempferol and quercetin. The present study isolated ten compounds including two kaempferol methyl ethers: 5-hydroxy-3,7,4'-trimethoxyflavone (1), 3-hydroxy-5,7,4'-trimethoxyflavone (6); four quercetin methyl ethers: retusin (5-hydroxy-3,7,3',4'-tetramethoxyflavone) (4), 3,5-dihydroxy-7,3',4'-trimethoxyflavone (5), 3,4'-dihydroxy-5,7,3'-trimethoxyflavone (7), and 3,5,7,3',4'-pentamethoxyflavone (9); ß-sitosterol (2); 5-hydroxy-1-(4'-hydroxyphenyl)eicosan-3-one (3); p-hydroquinone (8); and vanillic acid (10) from the rhizomes and fruit of Amomum koenigii J.F.Gmel. (Zingiberaceae). Their structures were determined by MS, NMR, and X-ray spectroscopic techniques. Among the methylated flavonols, 1, 4-7, and 9 were isolated for the first time from the rhizomes, while 1, 4, and 5 were isolated from the fruit. Compounds 2, 3, 7, 8, and 10 were reported for the first time from the species. Three main methylated flavonols 1, 4, and 5 were quantitatively analyzed in the rhizomes of A. koenigii by RP-HPLC-DAD; their contents were determined to be 1.81% (1), 1.38% (4), and 1.76% (5). The antimicrobial assay against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Aspergillus niger, Fusarium oxysporum, Candida albicans, and Saccharomyces cerevisiae and antioxidant DPPH scavenging test were performed for the isolated methylated flavonols.

Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin.

From the aerial parts of Scoparia dulcis L. (Scrophulariaceae) grown in Vietnam, four scopadulane-type diterpenoids (4-7), of which 7 is new and was given the trivial name scopadulcic acid C, together with nine known compounds were isolated. Their structures were elucidated by spectroscopic analyses. The absolute configurations of 4-7 were ascertained by applying the modified Mosher's method to iso-dulcinol (6). The isolation of the lignans nirtetralin and niranthin for the first time from S. dulcis is also of chemotaxonomic interest. The cytotoxic activity in KB cells, inhibitory effect on LPS/IFNgamma-induced NO production, inhibition of multidrug resistance (MDR), and antibacterial and antifungal activities of the scopadulane-type diterpenoids 4-7 were examined in this study.

New neolignans and lignans from Vietnamese medicinal plant Machilus odoratissima NEES.

Four new natural neolignans and lignans, which were given the trivial names odoratisols A-D (1-4), together with (-)-licarin A, kachirachirol B, obovatifol, and machilin-I were isolated from the air-dried bark of the Vietnamese medicinal plant Machilius odoratissima NEES (Lauraceae). Their absolute structures were determined on the basis of spectroscopic analyses including circular dichroism spectra.

Cytotoxic diterpenoids from Vietnamese medicinal plant Croton tonkinensis GAGNEP.

Six new ent-kaurane-type diterpenoids were isolated from the leaves of the endemic Vietnamese medicinal plant Croton tonkinensis GAGNEP. (Euphorbiaceae) together with three known ent-11alpha-acetoxy-7beta,14alpha-dihydroxykaur-16-en-15-one (1), ent-kaur-16-en-15-one 18-oic acid (5) and ent-18-hydroxykaur-16-ene (7). Their structures were determined by spectroscopic analyses to be ent-7beta-acetoxy-11alpha-hydroxykaur-16-en-15-one (2), ent-18-acetoxy-11alpha-hydroxykaur-16-en-15-one (3), ent-11alpha-acetoxykaur-16-en-18-oic acid (4), ent-15alpha,18-dihydroxykaur-16-ene (6), ent-11alpha,18-diacetoxy-7beta-hydroxykaur-16-en-15-one (8), and ent-(16S)-1alpha,14alpha-diacetoxy-7beta-hydroxy-17-methoxykauran-15-one (14). ent-Kaurane-type diterpenoids from Croton tonkinensis 2-4, 6, and 9-13, were tested for toxicity in the brine shrimp lethality assay. Compounds 9, 10, and 12 demonstrated significant activity, compounds 2, 3, 6, and 11 showed weak activity, and compounds 4 and 13 were inactive.