Liver X receptors agonists suppress NLRP3 inflammasome activation.

Inflammasomes are multiprotein complexes that control the production of IL-1ß and IL-18. NLRP3 inflammasome, the most characterized inflammasome, plays prominent roles in defense against infection, however aberrant activation is deleterious and leads to diseases. Therefore, its tight control offers therapeutic promise. Liver X receptors (LXRs) have significant anti-inflammatory properties. Whether LXRs regulate inflammasome remains unresolved. We thus tested the hypothesis that LXR's anti-inflammatory properties may result from its ability to suppress inflammasome activation. In this study, LXRs agonists inhibited the induction of IL-1ß production, caspase-1 cleavage and ASC oligomerization by NLRP3 inflammasome. The agonists also inhibited inflammasome-associated mtROS production. Importantly, the agonists inhibited the priming of inflammasome activation. In vivo data also showed that LXRs agonist prevented NLRP3-dependent peritonitis. In conclusion, LXRs agonists are identified to potently suppress NLRP3 inflammasome and the regulation of LXRs signaling is a potential therapeutic for inflammasome-driven diseases.

Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review.

Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors.

Comparison of the effects of DC031050, a class III antiarrhythmic agent, on hERG channel and three neuronal potassium channels.

AIM: This study was conducted to test the selectivity of DC031050 on cardiac and neuronal potassium channels. METHODS: Human ether-à-go-go related gene (hERG), KCNQ and Kv1.2 channels were expressed in CHO cells. The delayed rectifier potassium current (I(K)) was recorded from dissociated hippocampal pyramidal neurons of neonatal rats. Whole-cell voltage patch clamp was used to record the voltage-activated potassium currents. Drug-containing solution was delivered using a RSC-100 Rapid Solution Changer. RESULTS: Both DC031050 and dofetilide potently inhibited hERG currents with IC(50) values of 2.3 ± 1.0 and 17.9 ± 1.2 nmol/L, respectively. DC031050 inhibited the I(K) current with an IC(50) value of 2.7 ± 1.5 µmol/L, which was >1000 times the concentration required to inhibit hERG current. DC031050 at 3 µmol/L did not significantly affect the voltage-dependence of the steady activation, steady inactivation of I(K), or the rate of I(K) from inactivation. Intracellular application of DC031050 (5 µmol/L) was insufficient to inhibit I(K). DC031050 up to 10 µmol/L had no effects on KCNQ2 and Kv1.2 channel currents. CONCLUSION: DC031050 is a highly selective hERG potassium channel blocker with a substantial safety margin of activity over neuronal potassium channels, thus holds significant potential for therapeutic application as a class III antiarrhythmic agent.

Proteomic analysis of albumins and globulins from wheat variety Chinese Spring and its fine deletion line 3BS-8.

The relationship between chromosome deletion in wheat and protein expression were investigated using Chinese Spring and fine deletion line 3BS-8. Through 2-DE (2-D electrophoresis) analysis, no differentially expressed proteins (DEPs) were found in leaf samples; however, 47 DEPs showed at least two-fold abundance variation (p < 0.05) in matured wheat grains and 21 spots were identified by tandem MALDI-TOF/TOF-MS. Among the identified spots, four were cultivar-specific, including three (spots B15, B16, and B21) in Chinese Spring and one in 3BS-8 (spot B10). Among variety-different DEPs between Chinese Spring and 3BS-8, most spots showed a higher express profile in CS; only four spots showed up-regulated expression tendency in 3BS-8. An interesting observation was that more than half of the identified protein spots were involved in storage proteins, of which 11 spots were identified as globulins. According to these results, we can presume that the encoded genes of protein spots B15, B16, and B21 were located on the chromosome segment deleted in 3BS-8.

Wheat drought-responsive grain proteome analysis by linear and nonlinear 2-DE and MALDI-TOF mass spectrometry.

A comparative proteomic analysis of drought-responsive proteins during grain development of two wheat varieties Kauz (strong resistance to drought stress) and Janz (sensitive to drought stress) was performed by using linear and nonlinear 2-DE and MALDI-TOF mass spectrometry technologies. Results revealed that the nonlinear 2-DE had much higher resolution than the linear 2-DE. A total of 153 differentially expressed protein spots were detected by both 2-DE maps, of which 122 protein spots were identified by MALDI-TOF and MALDI-TOF/TOF mass spectrometry. The identified differential proteins were mainly involved in carbohydrate metabolism (26%), detoxification and defense (23%), and storage proteins (17%). Some key proteins demonstrated significantly different expression patterns between the two varieties. In particular, catalase isozyme 1, WD40 repeat protein, LEA and alpha-amylase inhibitors displayed an upregulated expression pattern in Kauz, whereas they were downregulated or unchanged in Janz. Small and large subunit ADP glucose pyrophosphorylase, ascorbate peroxidase and G beta-like protein were all downregulated under drought stress in Janz, but had no expression changes in Kauz. Sucrose synthase and triticin precursor showed an upregulated expression pattern under water deficits in both varieties, but their upregulation levels were much higher in Kauz than in Janz. These differentially expressed proteins could be related to the biochemical pathways for stronger drought resistance of Kauz.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis through Bcl-2/Bax Proteins Expression.

BACKGROUND: Deoxypodophyllotoxin, isolated from the Traditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant anti-tumor activity with strong toxicity in vitro and in vivo. OBJECTIVE: In this article, a series of deoxypodophyllotoxin derivatives were synthesized and their anti-tumor effectiveness was evaluated. METHODS: The anti-tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT assay method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. RESULTS: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29, and MG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. CONCLUSION: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

Anxiolytic potency of iridoid fraction extracted from Valeriana jatamansi Jones and its mechanism: a preliminary study.

Valeriana jatamansi Jones (V. jatamansi) has been widely used for treating anxiety and its mechanism involves many aspects including GABA level. This study aimed to evaluate the anxiolytic potency of an iridoid fraction extracted from the radix and rhizomes of V. jatamansi. The iridoid fraction was extracted by using D101 resin; its major components were analysed preliminarily by thin layer chromatography, ultraviolet spectrophotometry and high-performance liquid chromatography; and its anxiolytic effects at 6 mg/kg (low-dose), 9 mg/kg (medium-dose) and 12 mg/kg (high-dose) were evaluated using the elevated plus maze test, the light-dark box test, the Vogel's drinking conflict test, and the open field drink test. Its action mechanism was investigated using the ELISA. This study provided evidence on the anxiolytic potency of the iridoid fraction from V. jatamansi and revealed its action mechanism of regulating the GABA level.

Flavones and Lignans from the Stems of Wikstroemia scytophylla Diels.

BACKGROUND: The genus Wikstroemia has about 70 species, but only a limited number of species have been studied chemically. Wikstroemia indica has long been used as a traditional crude drug in China. However, there is no report about the bioactivity of Wikstroemia scytophylla. OBJECTIVE: This paper reports the chemical investigation and biological evaluation of the W. scytophylla. MATERIALS AND METHODS: The EtOAc extraction of W. scytophylla was isolated using chromatographic methods, and the compounds were analyzed by spectroscopic methods. The in vitro antitumor activities against five human cancer cell lines were performed according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. RESULTS: The chemical investigation of the stems of W. scytophylla resulted in the isolation of 12 compounds mainly including one biflavone (1), five flavones (2-6) compounds, and six lignans (7-12), in which compound 8 was a new natural product. Compounds 1 and 7-12 were evaluated for their antitumor activities while these compounds showed weak cytotoxicity with the half maximal inhibitory (IC50) values more than 40 µM. CONCLUSION: All of these compounds were isolated from this plant for the first time, and compounds 2-12 were first reported from genus Wikstroemia, in which compound 8 was a new natural product. Compounds 1 and 7-12 exhibited weak antitumor activities (IC50>40 µM). The chemotaxonomic significance of all the isolations was summarized. SUMMARY: The chemical investigation of the stems of W. scytophylla resulted in the isolation of 12 compoundsThe 12 compounds including six lignans (7-12), in which compound 8 was a new natural productThe isolated compounds 1 and 7-12 were evaluated for their antitumor activitiesThe chemotaxonomic significance of all the isolations was summarized. Abbreviations used: MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; IC50: Half maximal inhibitory; HL-60: Human leukemia cell line; SMMC-7721: Human hepatocellular carcinoma cell line; A549: Human lung tumor cell line; MCF-7: Human breast cancer cell line; SW480: Human colon cancer cell line; MS: Mass spectrometry; NMR: Nuclear Magnetic Resonance.

A new phenolic glycoside from Lindera nacusua.

The present study was designed to investigate the chemical constituents of Lindera nacusua and their antitumor activities. A new phenolic glycoside, namely 1-O-3-hydroxyphenyl-5-methoxyphenol-(6'-O-vanilloyl)-ß-d-glucopyranoside (1), together with five known phenolic glycosides (2-6), two anthraquinones (7, 8) and two γ-butanolides (9, 10), was isolated, and its structure was elucidated by spectroscopic and chemical methods. Compounds 1-10 were screened for their in vitro cytotoxicities against HL-60, SMMC-7721, A549, MCF-3 and SW480 cell lines by the MTS method. Compounds 9 and 10 showed moderate cytotoxicities with IC50 values ranging from 17.40 to 35.21 µM.

Antitumor constituents from Anthriscus sylvestris (L.) Hoffm.

Bioassay-guided chemical investigation of the roots of Anthriscus sylvestris (L.) Hoffm. resulted in the isolation of nine compounds, whose structures were determined by spectroscopic methods. Compound 1 was isolated from this plant for the first time and compounds 3 and 9 were first found from this genus. Different polar fractions of A. sylvestris extract and compounds 1, 6-8 and 9 were evaluated for antitumor activities against HepG2 (human hepatocellular carcinoma), MG-63 (human osteosarcoma cells), B16 (melanoma cells) and HeLa (human cervical carcinoma cells) lines by the MTT method. The petroleum ether fraction of A. sylvestris extract exhibited excellent inhibitory activity with an IC50 value of 18.3 µg/ml. Among the isolates from the petroleum ether fraction, compound 7 showed significant inhibition against the growth of the four tumor cells with IC50 values ranging from 12.2-43.3 µg/ml.