Prenylated flavonoids from Ficus hirta induces HeLa cells apoptosis via MAPK and AKT signaling pathways.

A pair of undescribed enantiomers, (±) ficusflavonid A (1a/1b), along with five known analogues, were isolated from the roots of Ficus hirta. Their structures were determined by the analysis of extensive spectroscopic data (including UV, IR, HRESIMS and NMR). Two enantiomers (1a and 1b) were successfully separated by chiral chromatographic column and their absolute configurations were assigned by the comparison of experimental and calculated ECD data. The cytotoxicity of all the isolates against HeLa, MCF-7, HepG2 and H460 cell lines were evaluated by MTT assay. Among them, 4 suppressed the proliferation of HeLa cells with the IC50 value of 28.88 µM. Furthermore, the apoptotic effect of 4 on HeLa cells and the level of several crucial proteins in AKT/MAPKs signaling pathways were analyzed by flow cytometer and western blot assay. As a result, 4 induced HeLa cell apoptosis in a dose dependent manner and significantly increased the protein levels of p-JNK and p-p38, whereas distinctly reduced the expression of p-AKT, and p-ERK. Thus, compound 4 might induce HeLa cells apoptosis via MAPK and AKT signaling pathways, which could be considered as a potential leading compound for the development of anticancer drugs.

Chemical Constituents from Endophytic Fungus Annulohypoxylon cf. stygium in Leaves of Anoectochilus roxburghii.

The chemical investigation on endophytic fungus Annulohypoxylon cf. stygium in leaves of Anoectochilus roxburghii (Wall.) Lindl. has been performed. Sixteen compounds were isolated and their structures were identified as (-)-notoamide A, (-)-notoamide B, (+)-versicolamide B, notoamide C, notoamide D, stephacidin A, sterigmatocystin, dihydrosterigmatocystin, secosterigmatocystin, versiconol, averufanin, kipukasin D, kipukasin E, diorcinal, palmarumycin CP2 and (-)-(3R)-mellein methyl ether, respectively, by spectroscopic analysis and comparison with literature data. All the compounds were isolated from Annulohypoxylon genus for the first time. Sterigmatocystin and palmarumycin CP2 showed selective cytotoxic activities against HepG2, HeLa, MCF-7 and HT-29.

Bioactive prenylated xanthones from the stems of Cratoxylum cochinchinense.

Cochinchinones M-U (1-9), together with 12 known compounds (10-21), were isolated from the stems of Cratoxylum cochinchinense (Lour.) Blume. Their structures were determined on the basis of extensive spectroscopic data analyses. In addition, their retinoid X receptor-α transcriptional activities were evaluated using an in vitro assay.

[Chemical constituents and cytotoxicity assay research in small polar substances from Vitis thunbergii var. taiwaniana].

This article studied the chemical constituents from the aerial part of Vitis thunbergii var. taiwaniana. The 60% ethanol extract was eluted with 95% ethanol though HP-20 macroporous adsorption resin column. 12 compounds, including (1) betulinic acid, (2)2, 2, 2'-bis (4-hydroxyphenyl) propane bis (2, 3-epoxypropyl) ether, (3) eriodictyol, (4) trans-ε-viniferin, (5) (+)-cis-ε-viniferin, (6) kobophenol A, (7) ampelopsin A, (8) nepalensinol B, (9) cis-miyabenol C, (10) cis-vitisin B, (11) cis-gnetin H and (12) (+)-hopeaphenol, were separated by using normal phase silica gel, ODS, Sephdadex LH-20 column chromatographies and semi-preparative or preparative HPLC. Compounds 2, 5, 6, 8, 9, 10, 11 were separated from the genus Vitis for the first time and compounds 3, 7, 12 were separated from Vitis thunbergii var. taiwaniana for the first time. At a concentration of 50 µmol · L(-1), compound 6, 7 and 11 showed strong cytotoxicity against MCF-7 cell lines with the inhibition rate of 66.58%, 57.16%, 52.84%, respectively.

[Chemical constituents from Elephantopus tomentosus].

OBJECTIVE: To study the chemical constituents of Elephantopus tomentosus. METHOD: The compounds were isolated by repeated HP20 macro porous adsorption resin column combined with Sephadex LH-20, ODS and silica gel chromatographies. The structures were identified on the basis of extensive spectroscopic data analysis and by comparison of their spectral data reported. RESULT: Eighteen compounds were identified as 2-deethoxy-2beta-hydroxyphantomolin (1), 2beta-hydroxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (2), 2beta-methoxy-2-deethoxyphantomolin (3), 2beta-methoxy-2-deethoxy-8-O-deacylphantomolin-8-O-tiglinate (4), molephantin (5), molephantinin (6), tricin (7), luteolin (8), quercetin (9), 3beta-friedelinol (10), 3beta-hydroxyolean-12-en-28-oic acid (11), 3, 5-di-O-caffeoyl quinic acid (12), 3,4-di-O-caffeoyl quinic acid (13), syringaresinol-4-beta-D-glucopyranoside (14), xylogranatinin (15), byzantionoside B (16), 2'-hydroxycinnamaldehyde (17), and caffeic acid ethyl ester (18). CONCLUSION: Compounds 9, 11, 14-18 were separated from Elephantopus for the first time.

Tumor suppressor menin represses paired box gene 2 expression via Wilms tumor suppressor protein-polycomb group complex.

Tumor suppressor menin, the product of the MEN1 gene, plays a key role in controlling histone 3 lysine 4 trimethylation (H3K4me3) and gene transcription, which can regulate proliferation, apoptosis, and differentiation. However, little is known as to whether menin controls gene expression and cell proliferation and survival via regulating Polycomb group (PcG) protein complex/H3K27me3. Here we show that menin specifically represses transcription factor Paired box gene 2 (Pax2) through PcG-mediated H3K27me3 and Wilms tumor suppressor protein (WT1), a zinc finger domain-containing DNA-binding protein. Menin does not directly bind to the Pax2 locus, instead, it up-regulates WT1 expression. WT1 recruits PcG complex to the Pax2 promoter and represses expression of Pax2 through PcG-dependent H3K27me3. Moreover, WT1 also interacts with DNA methyltransferase 1 (DNMT1), and recruits DNMT1 to the Pax2 promoter, resulting in hypermethylation of CpG in the Pax2 promoter. Together, these studies have uncovered a novel epigenetic mechanism whereby menin regulates H3K27me3 and promoter DNA methylation via WT1 and suggest that WT1 protein plays an important, yet previously unappreciated role in regulating the function of the menin/PcG axis, H3K27 methylation, and DNA methylation, resulting in repression of gene transcription.

Lignans and phenylpropanoids from the roots of Ficus hirta and their cytotoxic activities.

One undescribed lignan, one new natural product, along with fourteen known compounds, were isolated from the roots of Ficus hirta. The structures of the isolates were elucidated by comprehensive spectroscopic technologies, including UV, IR, HRESIMS, and NMR. The absolute configuration of 1 was determined by comparison of experimental and calculated ECD data. The cytotoxicity of all the compounds against HeLa and HepG2 cell lines was evaluated and compound 7 showed considerable cytotoxic effect towards HepG2 cells. Also, the apoptotic effect of 7 on HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-p38) in MAPK (Mitogen-activated protein kinases) pathways were studied by flow cytometry and western blotting experiment. As a result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK signaling pathway.

Phakefustatins A-C: Kynurenine-Bearing Cycloheptapeptides as RXRα Modulators from the Marine Sponge Phakellia fusca.

A neutral-loss scanning mass method was used to explore new kynurenine-containing cycloheptapeptides, phakefustatins A-C (1-3), from the marine sponge Phakellia fusca. Their structures were elucidated by spectroscopic analysis and the advanced Marfey's method. 1 was total synthesized via a final-stage ozonolysis strategy by the combination of solid/solution-phase synthesis. Phakefustatin A (1) was identified as a RXRα modulator to inhibit cancer cell growth, and its pharmacophores could be Kyn and guanidine groups.

Septosones A-C, in Vivo Anti-inflammatory Meroterpenoids with Rearranged Carbon Skeletons from the Marine Sponge Dysidea septosa.

Three unusual meroterpenoids, septosones A-C (1-3), were isolated from the marine sponge Dysidea septosa. The structures were determined by analysis of spectroscopic data combined with single-crystal X-ray diffraction and ECD calculations. Septosone A (1) features an unprecedented "septosane" carbon skeleton, whereas septosones B (2) and C (3) share a rare spiro[4.5]decane motif. Septosone A showed in vivo anti-inflammatory activity in CuSO4-induced transgenic fluorescent zebrafish likely through inactivation of the NF-κB signaling pathway.

Secondary metabolites of petri-dish cultured Antrodia camphorata and their hepatoprotective activities against alcohol-induced liver injury in mice.

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.

RXRα transcriptional inhibitors from the stems of Calophyllum membranaceum.

Bioassay-guided fractionation of the 60% ethanol extract of the stems of Calophyllum membranaceum using the RXRα transcription activation assay led to the isolation of two new chromanones, calopolyanic acid methyl ester (1) and isopinetoric acid methyl ester (2), two new xanthones, calophylixanthones A-B (3-4), and one new C-glycoside, calophymembranside C (5), along with 13 known compounds. Their structures were elucidated on the basis of extensive spectroscopic data. Compounds 5, 11 and 18 showed transcriptional inhibitory activity of RXRα with 50% inhibitory concentration (IC50) values of 29.95 ± 1.08, 31.06 ± 9.02, and 25.88 ± 1.62 µM, respectively.