[Research progress in raw and processed Raphani Semen and prediction of quality markers].

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.

Two new meroterpenoids from the bark of Cinnamomum cassia and their antioxidant activity.

Two new (1 and 2) meroterpenoids were isolated from the bark of Cinnamomum cassia. Their structures were determined by spectroscopic analyses and chemical methods. Antioxidant activities of 1 and 2 were evaluated by the ORAC and DPPH radical scavenging assays, and the results revealed that compound 2 displayed oxygen radical absorbance capacity. The discovery of compounds 1 and 2 added new members of this kind of natural product.

Novel quinoline-based derivatives as the PqsR inhibitor against Pseudomonas aeruginosa PAO1.

AIMS: The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa. METHODS AND RESULTS: The results showed that compound 1 suppressed the expression of QS-related genes and showed the best inhibitory activity to the pqs system of wild-type Ps. aeruginosa PAO1 with an IC50 of 20.22 µmol L-1 . The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration-dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand-binding domain of the Lys-R type transcriptional regulator PqsR as a competitive antagonist. CONCLUSIONS: The quinoline-based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced. SIGNIFICANCE AND IMPACT OF STUDY: The study showed that the quinoline-based derivatives could be used as an anti-virulence agent for treating Ps. aeruginosa infections.

Cycloartane-type triterpenoids from the root of Astragalus membranaceus var. mongholicus.

Three new (1-3) and 11 known (4-14) cycloartane-type triterpenoids were isolated from the root of Astragalus membranaceus var. mongholicus. Their structures were determined by spectroscopic analyses and chemical methods. Cycloartane-type triterpenoids are a class of major bioactive constituents in the root of A. membranaceus var. mongholicus, and the discovery of compounds 1-3 added new members of this kind of natural product. [Formula: see text].

Novel 2, 8-bit derivatives of quinolines attenuate Pseudomonas aeruginosa virulence and biofilm formation.

Signal molecules are stimulators of multiple quroum-sensing virulence and biofilm formation. Small molecule analogues have been suspected as a potent inhibitor in therapeutic strategy. Herein, we synthesized a series of small molecule compounds from the 2, 8-bit derivatives of quinoline by Suzuki coupling reaction. We found that these compounds have the biofilm inhibitory effect in normal condition instead of phosphate limitation state. Furthermore, lacZ reporter strain assay and rhamnolipids as well as pyocyanin experiments showed that these compounds did not affect las and pqs system but reduced the expression of rhl. All these results suggest that quinoline derivatives can be treated as potent inhibitors against biofilm and reduce virulence through the rhl system. This research will be useful in designing new quorum sensing inhibitors to attenuate the infection of bacteria.

Novel Coumarin Derivatives Inhibit the Quorum Sensing System and Iron Homeostasis as Antibacterial Synergists against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound 4t was identified as the most effective biofilm inhibitor (IC50 = 3.6 µM). Further mechanistic studies have confirmed that 4t not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in P. aeruginosa. Additionally, 4t significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that 4t is a potentially novel antibacterial synergist candidate to treat bacterial infections.

Sesquiterpene lactones from Artemisia vulgaris L. as potential NO inhibitors in LPS-induced RAW264.7 macrophage cells.

Twelve new guaianolide sesquiterpene lactones (1-12), along with ten known analogs (13-22) were isolated from an EtOH extract of the dried aerial parts of Artemisia vulgaris L. The new structures were elucidated via abundant spectroscopic data analyses (HRESIMS, IR, 1D, and 2D NMR), and the absolute configurations of these compounds were determined by X-ray crystallography and ECD calculations. The compounds (1-22) were identified as guaiane-type sesquiterpenes with characteristic α-methylene-γ-lactone and α,ß-unsaturated carbonyl moieties. All compounds were tested for their inhibitory activity against NO production in lipopolysaccharide-stimulated RAW264.7 macrophages. The isolated sesquiterpenoids dose-dependently exhibited an NO production inhibitory activity by inhibiting the expression of inducible NO oxidase (iNOS) and cyclooxygenase-2 (COX-2) with IC50 values ranging from 1.0 to 3.6 µM. The inhibitory effect on the NO production of the compounds (1-4 and 6-22) is better than that of the positive control (dexamethasone). The different substitutions of compounds on C-8 influence anti-inflammatory effects, as evidenced by the in silico analysis of related binding interactions of new compounds (1-12) with iNOS.

New 3',8''-linked biflavonoids from Selaginella uncinata displaying protective effect against anoxia.

Seven 3',8''-linked bioflavonoids, including one new compound, (2''S)-2'', 3''-dihydroamentoflavone-4'-methyl ether and six known compounds: (2S)-2,3- dihydroamentoflavone-4'-methyl ether, (2S,2''S)-2,3,2'',3''-tetrahydroamento- flavone-4'-methyl ether, (2S,2''S)-tetrahydroamentoflavone, (2S)-2,3-dihydro- amentoflavone and (2''S)-2'',3''-dihydroamentoflavone (6) and amentoflavone, were isolated from the 60% ethanolic extract of Selaginella uncinata (Desv.) Spring. The structures of these compounds were elucidated mainly by analysis of their 1D and 2D NMR spectroscopic data, and their absolute configurations were determined by circular-dichroism (CD) spectroscopy. All the seven compounds showed protective effect against anoxia in the anoxic PC12 cells assay, in which compound 6 displayed particularly potent activity.

[Study on the extraction technology of total flavonoids from Selaginella uncinata].

OBJECTIVE: To optimize the extraction technology of total flavonoids and improve the extraction ratio of total flavonoids from Selaginella uncinata. METHODS: Using the content of flavonoids as the index determined by UV spectrophotometry, chose single factor experiment to investigate the total flavonoids content influenced by four factor ethanol concentration, extracting time, extraction times and solvent content on the influence of extraction efficiency. And on the basis, L9 (3(4)) orthogonal experiment was carried out. RESULTS: The ethanol reflux extraction conditions were as tollows: extracted in 60% ethanol (solid-liquid rate at 1: 35) for 3 times and heated for 1.5 hours per time. CONCLUSION: The optimum extraction by the orthogonal design method is rational and feasible, provides experimental basis for improving the content of the total flavonoids and further scientific theoretical basis for industrial production of the total flavonoids from Selaginella uncinata.

Design, synthesis and evaluation of halogenated furanone derivatives as quorum sensing inhibitors in Pseudomonas aeruginosa.

The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.

Strigolactones: a plant phytohormone as novel anti-inflammatory agents.

Strigolactones (SLs) are a novel class of plant hormones with enormous potential for the prevention and treatment of inflammation. To further investigate the anti-inflammatory activities of SLs, a representative SL, GR24, and the reductive products of its D-ring were synthesized and their anti-inflammatory activities were fully evaluated on both in vitro and in vivo models. Among these compounds, the two most active optical isomers (2a and 6a) demonstrated strong inhibitory activity on the release of inflammatory cytokines, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) by blocking the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways; they also greatly inhibited the migration of neutrophils and macrophages in fluorescent protein labeled zebrafish larvae. These results identified the promising anti-inflammatory effects of SLs, and suggested that both the absolute configuration of SL and the α,ß-unsaturated D-ring structure are essential for the observed anti-inflammatory activity.

Four new biflavonoids from Selaginella uncinata and their anti-anoxic effect.

The 60% ethanolic extract of Selaginella uncinata (Desv.) Spring possessed potent anti-anoxic effect in the anoxic PC12 cell assay. A phytochemical study of its EtOAc-soluble part led to the isolation of four new and three known biflavonoids. Their structures were established on the basis of physico-chemical properties and spectroscopic analysis. The absolute configurations of the new compounds were determined with the aid of circular dichroism (CD) spectroscopy. Compounds 4 and 5 showed potent anti-anoxic effect in the anoxic PC12 cell assay.