Specific inactivation of an antifungal bacterial siderophore by a fungal plant pathogen.

Bacteria and fungi secrete many natural products that inhibit each other's growth and development. The dynamic changes in secreted metabolites that occur during interactions between bacteria and fungi are complicated. Pyochelin is a siderophore produced by many Pseudomonas and Burkholderia species that induces systemic resistance in plants and has been identified as an antifungal agent. Through imaging mass spectrometry and metabolomics analysis, we found that Phellinus noxius, a plant pathogen, can modify pyochelin and ent-pyochelin to an esterification product, resulting in reduced iron-chelation and loss of antifungal activity. We also observed that dehydroergosterol peroxide, the fungal metabolite, is only accumulated in the presence of pyochelin produced through bacteria-fungi interactions. For the first time, we show the fungal transformation of pyochelin in the microbial interaction. Our findings highlight the importance of understanding the dynamic changes of metabolites in microbial interactions and their influences on microbial communities.

Bioactive constituents of Lindernia crustacea and its anti-EBV effect via Rta expression inhibition in the viral lytic cycle.

ETHNOPHARMACOLOGICAL RELEVANCE: Lindernia crustacea (L.) F.Muell. (Scrophulariaceae) was selected for phytochemical investigation owing to its traditional use against human herpes virus infection and its anti-Epstein-Barr virus (EBV) effect. AIMS OF THE STUDY: The present study focused on the phytochemical investigation of L. crustacea including the isolation and structure determination of its biologically active compounds. Compounds with anti-EBV effects were also investigated. MATERIALS AND METHODS: The EtOH extract of L. crustacea was subsequently partitioned using different solvents. The EtOAc fraction was subjected to several chromatographic methods to obtain pure compounds. The structures of all isolates were established by spectroscopic analysis and compared with previously reported physical data. The anti-EBV effect was evaluated in an EBV-containing Burkitt's lymphoma cell line (P3HR1) to study the expression of EBV lytic proteins. RESULTS: Thirty-three compounds, including one diterpene (1), four anthraquinones (2-5), two ionones (6 and 7), fourteen phenylpropanoid glycosides (8-21), five flavonoids (22-26), one lignan glycoside (27), one phenethyl alcohol glycoside (28), one phenylpropene glycoside (29), one glucosyl glycerol derivative (30), one furanone (31), and two cinnamic acid derivatives (32 and 33), were isolated from the ethanolic extract of the plant. All isolated compounds were obtained for the first time from Lindernia sp. The evaluation of the anti-EBV activity of L. crustacea crude extract, partitioned fractions, and constituents was performed for the first time. Phytol (1), aloe-emodin (2), byzantionoside B (7), a mixture of trans-martynoside (8) and cis-martynoside (9), a mixture of trans-isomartynoside (10) and cis-isomartynoside (11), luteolin-7-O-ß-D-glucopyranoside (24), and apigenin-7-O-[ß-D-apiofuranosyl (1→6)-ß-D-glucopyranoside] (25) exhibited significant inhibitory effects on the EBV lytic cycle at 20 µg/mL in the immunoblot analysis. On the other hand, (6R,7E,9R)-3-oxo-α-ionol-ß-D-glucopyranoside (6) and a mixture of trans-dolichandroside A (12) and cis-dolichandroside A (13) showed moderate anti-EBV activity at 20 µg/mL. CONCLUSIONS: L. crustacea and its active isolates could be developed as potential candidates against EBV. Our findings provide scientific evidence for the traditional use of L. crustacea for its antiviral effects.

2-Bromo-4'-methoxychalcone and 2-Iodo-4'-methoxychalcone Prevent Progression of Hyperglycemia and Obesity via 5'-Adenosine-Monophosphate-Activated Protein Kinase in Diet-Induced Obese Mice.

Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4'-methoxychalcone (compound 5) and 2-iodo-4'-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5'-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4'-methoxychalcone and 2-iodo-4'-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.

Anti-Lymphangiogenesis Components from Zoanthid Palythoa tuberculosa.

Three new compounds, tuberazines A-C (1-3), and eleven known compounds (4-14) were obtained from the ethanolic extract of Taiwanese zoanthid Palythoa tuberculosa. Compounds 1-4 are rare marine natural products with a pyrazine moiety, and compound 5 is a tricyclic tryptamine derivative isolated from nature for the first time. The structures of all isolated metabolites were determined by analyzing their IR, Mass, NMR, and UV spectrometric data. The absolute configuration of 1 was confirmed by comparing the trend of experimental electronic circular dichroism (ECD) with calculated ECD spectra. The anti-lymphangiogenic activities of new compounds were evaluated in human lymphatic endothelial cells (LECs). Of these, new compound 3 displayed the most potent anti-lymphangiogenesis property by suppressing cell growth and tube formation of LECs.

Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core.

Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds.

In vitro anti-diabetic effect and chemical component analysis of 29 essential oils products.

Twenty-nine commercial essential oil (EO) products that were purchased from the Taiwan market, including three different company-made Melissa officinalis essential oils, were assayed on their glucose consumption activity and lipid accumulation activity on 3T3-L1 adipocytes. The EOs of M. officinalis were significantly active in both model assays. By contrast, EOs of peppermint, lavender, bergamot, cypress, niaouli nerolidol, geranium-rose, and revensara did not increase glucose consumption activity from media, but displayed inhibited lipid accumulation activity (65-90% of lipid accumulation vs. the control 100%). Because of the promising activity of M. officinalis EOs, three different products were collected and compared for their gas chromatography chemical profiles and bioactivity. The Western blot data suggest that the key factors of the adenosine monophosphate-activated protein kinase/acetyl-CoA carboxylase pathway can be mediated by M. officinalis EOs. Together with biodata, gas chromatography-mass spectrometry profiles suggested mixtures of citrals and minor compounds of M. officinalis EOs may play an important role on effect of antidiabetes.

Highly Selective Continuous-Flow Synthesis of Potentially Bioactive Deuterated Chalcone Derivatives.

The selective synthesis of various dideuterochalcones as potentially bioactive deuterium-labeled products is presented, by means of the highly controlled partial deuteration of antidiabetic chalcone derivatives. The benefits of continuous-flow processing in combination with on-demand electrolytic D2 gas generation has been exploited to avoid over-reaction to undesired side products and to achieve selective deuterium addition to the carbon-carbon double bond of the starting enones without the need for unconventional catalysts or expensive special reagents. The roles of pressure, temperature, and residence time proved crucial for the fine-tuning of the sensitive balance between the product selectivity and the reaction rate. The presented flow-chemistry-based deuteration technique lacks most of the drawbacks of the classical batch methods, and is convenient, time- and cost-efficient, and safe.

Bioactive constituents of Cirsium japonicum var. australe.

Cirsium japonicum var. australe, used as a folk medicine in Taiwan, has been employed traditionally in the treatment of diabetes and inflammatory symptoms. Bioactivity-guided fractionation of its ethanolic extract, utilizing centrifugal partition chromatography monitored by DPPH-TLC analysis, led to the isolation of three new acetylenic phenylacrylic acid esters (1-3) and two new polyacetylenes (4 and 5), together with seven known compounds (6-12). The structures of 1-5 were elucidated by spectroscopic methods including 1D and 2D NMR techniques. The absolute configurations of 4 and 7 were determined utilizing Mosher's method and ECD/CD experiments. The DPPH scavenging activity of the constituents isolated from the C. japonicum var. australe ethanolic extract was evaluated. The potential antidiabetic activity of some of the isolates was evaluated using in vitro cellular glucose uptake and oil red staining assays.

An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii.

The addition of a DNA methyltransferase inhibitor, 5-azacytidine, to Aspergillus sydowii fungus culture broth changed its secondary metabolites profile. Analysis of the culture broth extract led to the isolation of three new bisabolane-type sesquiterpenoids: (7S)-(+)-7-O-methylsydonol (1), (7S,11S)-(+)-12-hydroxysydonic acid (2) and 7-deoxy-7,14-didehydrosydonol (3), along with eight known compounds. The isolated compounds were evaluated for their anti-diabetic and anti-inflammatory activities. Among the isolates, (S)-(+)-sydonol (4) did not only potentiate insulin-stimulated glucose consumption but also prevented lipid accumulation in 3T3-L1 adipocytes. Additionally, (S)-(+)-sydonol (4) exhibited significant anti-inflammatory activity through inhibiting superoxide anion generation and elastase release by fMLP/CB-induced human neutrophils. This is the first report on isolating a secondary metabolite with anti-diabetic and anti-inflammatory activities from microorganisms.

Synthesis of chalcone derivatives as potential anti-diabetic agents.

Chalcones bearing electron donating or electron withdrawing substitutions were prepared and their glucose uptake activity was evaluated. Chalcone derivatives were synthesized in one step protocol with high purity and yield. Chalcones with chloro, bromo, iodo and hydroxy substitutions at position 2 on A-ring exhibited the highest activity with glucose medium concentration (210 to 236 mg/dl) compared to pioglitazone and rosiglitazone (230 and 263 mg/dl, respectively). Also chalcones with iodo substitution at position 3 on A-ring were comparably active (≤238 mg/dl). The structure-activity relationship of the tested chalcones was studied and the findings were supported statistically.