Candida Biofilm Disrupting Ability of Di-rhamnolipid (RL-2) Produced from Pseudomonas aeruginosa DSVP20

Biosurfactant produced from Pseudomonas aeruginosa DSVP20 was evaluated for its potential to disrupt Candida albicans biofilm formed on polystyrene (PS) surfaces in this investigation. P. aeruginosa DSVP20 exhibited optimum production of biosurfactant (5.8 g?L^?1) after 96 h of growth with an ability to reduce surface tension of the aqueous solution from 72 to 28 mN?m^?1. Analysis of purified biosurfactant with FT-IR, ¹H and ¹³C NMR and MALDI-TOF MS revealed it to be di-rhamnolipid (RL-2) in nature. Biofilm disrupting ability of RL-2 (0.16 mg?mL^?1) on Candida cells when checked using XTT reduction assay revealed that about 50 % of the cells remain adhered to 96-well plate after 2 h of treatment, while up to 90 % reduction in pre-formed C. albicans biofilm on PS surface was observed with RL-2 (5.0 mg?mL^?1) in a dose-dependent manner. Microscopic analyses (SEM and CLSM) further confirm the influence of RL-2 on disruption of Candida biofilm extracellular matrix on PS surface which can be exploited as a potential alternative to the available conventional therapies.     

The Effects of Berry Extracts on Oxidative Stress in Cultured Cardiomyocytes and Microglial Cells: A Potential Cardioprotective and Neuroprotective Mechanism

Oxidative stress is a key underlying factor in cognitive decline and atherosclerosis. Oxidative stress occurs at the cellular level with an imbalance between reactive oxygen species and reactive nitrogen species and a deficiency in antioxidants. Mounting evidence suggests that berry flavonoids may promote cellular health by exerting antioxidant properties. Black currant and various berry extracts were tested in microglia (BV-2) and cardiomyocyte (HL-1) cell lines to study their biological effects. The principal ingredients in black currant and cranberry extract–delphinidin 3-rutinoside (D3R) and cyanidin 3-glucoside (C3G), were also assessed. A menadione-induced oxidative stressor was used, and its output was quantified to detect oxidative stress (CellROX^TM). Black currant extract had similar antioxidant effects as N-acetylcysteine (NAC) in HL-1 cells with regard to cellular protection, whereas cranberry extract was ineffective. In contrast, cranberry extract was comparable in effectiveness to black currant extract in BV-2 cells. D3R and C3G also reduced oxidative stress similarly to whole berry extracts, which indicates that these ingredients may confer the antioxidant effects of berries. Black currant and cranberry extracts inhibit oxidative stress in microglial and cardiomyocyte cell lines. Black currant extract was more effective in reducing oxidative stress in the HL-1 cells, whereas cranberry extract was comparable in reducing oxidative stress in the BV-2 cells. The results suggest that berry flavonoids exert neuro- and cardioprotective effects.     

Anti-Neuroinflammatory Components from Clausena lenis Drake

Clausena lenis Drake (C. lenis) is a folk medicinal herb to treat influenza, colds, bronchitis, and malaria. The 95% and 50% ethanol extract of C. lenis showed significant nitric oxide (NO) inhibition activity in BV-2 microglial cells stimulated by lipopolysaccharide (LPS). Bio-guided isolation of the active extract afforded five new compounds, including a chlorine-containing furoquinoline racemate, (±)-claulenine A (1), an amide alkaloid, claulenine B (2), a prenylated coumarin, claulenin A (3), a furocoumarin glucoside, clauleside A (4), and a multi-prenylated p-hydroxybenzaldehyde, claulenin B (5), along with 33 known ones. Their structures were determined via spectroscopic methods, and the absolute configurations of new compounds were assigned via the electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analysis. Compounds 2, 23, 27, 28, 33, and 34 showed potent anti-neuroinflammatory effects on LPS-induced NO production in BV-2 microglial cells, with IC₅₀ values in the range of 17.6–40.9 μM. The possible mechanism was deduced to interact with iNOS through molecular docking.     

Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells

Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia play an important role in human neurodegenerative disorders. Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxidative agent in Chinese medicine, attenuates excessive production of NO and proinflammatory cytokines such as TNF-alpha and IL-1betal in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-alpha, and IL-1beta in BV-2 cells was largely inhibited in the presence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced expression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated attenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-kappaB in BV-2 cells. The results indicate that celastrol effectively attenuated NO and proinflammatory cytokine production via the inhibition of ERK1/2 phosphorylation and NF-kappaB activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.     

Alashinol H,an epoxylignan with an unusual six-membered cyclic hemiacetal from Syringa pinnatifolia

A new 7, 9′-epoxylignan, alashinol H (1), which features a rare six-membered cyclic hemiacetal, was isolated from the stem barks of Syringa pinnatifolia. The structure was elucidated based on spectroscopic data including HRESIMS and NMR. Its absolute configuration was resolved by GIAO NMR shifts and ECD calculations. A putative biosynthetic pathway of this compound is proposed. Alashinol H showed a moderate inhibitory effect against NO production in BV-2 murine microglia cells.     

Stachyodin A,a pterocarpan derivative with unusual spirotetrahydrofuran ring from the roots of Indigofera stachyodes

Stachyodin A (1), a rearrangement product of pterocarpan featuring a 6/5/5/6 tetracyclic ring system with an unusual spirotetrahydrofuran ring, and stachyodin B (2), a new dihydrochalcone, along with five known analogues (3–7) were isolated from the roots of Indigofera stachyodes. The structures of 1 and 2 were elucidated on the basis of their HRESIMS and NMR spectroscopic data, and their absolute configurations were determined by X-ray crystallographic analysis and electronic circular dichroism (ECD) data, respectively. Compounds 2–4 showed inhibition of nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells.     

Genkwalathins A and B,new lathyrane-type diterpenes from Daphne genkwa

Screening for new natural anti-neuroinflammatory compounds was performed with the traditional folk medicine Genkwa Flos, which potently inhibited nitric oxide (NO) production by LPS-activated microglial BV-2 cells. Two new lathyrane-type diterpenes, genkwalathins A (1) and B (2), and 14 known daphnane-type diterpenes (3–16) were isolated. The lathyrane-type diterpenes were isolated for the first time from the Thymelaeaceae family in this study. Compounds 1 and 2 moderately inhibited LPS-induced NO production in BV-2 cells without affecting cell viability, while six daphnane-type diterpenes (3, 4, 6, 7, 9 and 10) potently reduced NO production with IC₅₀ values less than 1 μM, although they did display weak cytotoxicity. A structure–activity relationship study on the daphnane-type diterpenes indicated that the stereochemistry at C-19, the benzoate group at C-20, and the epoxide moiety could be important for their anti-neuroinflammatory effects.     

Metabolic responses of BV-2 cells to puerarin on its polarization using ultra-performance liquid chromatography–mass spectrometry

Microglia are the primary immune cells in the central nervous system with functional plasticity. They can be activated into M1 and M2 phenotypes when neuroinflammation-related diseases occur. M1 phenotype cells produce pro-inflammatory mediators that cause neuroinflammation and the M2 phenotype can secrete anti-inflammatory cytokines that protect neurons from damage. Therefore, inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for treating neuroinflammation-related diseases. Puerarin has been demonstrated to exert anti-inflammatory and neuroprotective effects. However, the role of puerarin in regulating microglia polarization and its reaction mechanism has not been fully elucidated. In this paper, a metabolomics approach with ultra-performance liquid chromatography–mass spectrometry was performed to investigate the metabolic changes of BV-2 cells in different phenotypes and test the effects of puerarin on polarization. Thirty-nine metabolites were identified as the biomarkers related to the polarization of BV-2 cells and puerarin intervention reverted the content of most of the biomarkers. Our study demonstrated that puerarin could play a key role in M1/M2 polarization of BV-2 cells from a perspective of metabolomics, and it could regulate the balance between promotion and suppression of inflammation.     

Diméthyl 3-benzyl-2-(4-méthyl-2,5-dioxoimidazolidin-1-yl)butanedioate

There are two symmetry-independent formula units of the title compound, dimethyl 3-benzyl-2-(4-methyl-2,5-di­oxo­imid­azol­idin-1-yl)­butane­dioate, C₁₇H₂₀N₂O₆, per cell. The two symmetry-independent molecules differ in their configuration and are diastereomers. This structural study confirms a new side reaction during the synthesis of seven-membered cyclopeptides. The stereochemistry of both diastereomers has been established.     

Phase transition in dichloro(ethylenediamine) copper(II) crystals [(En)CuCl(μ3-Cl)] and their structure

Dichloro(ethylenediamone)copper(II) crystals undergo a phase transition at 138 K. X-ray crystal structure analysis at 123 K and 173 K showed that the phase transition is associated with ordering of both carbon atoms; space group changes from P2₁/m to P2₁/c, and the c parameter of the unit cell is nearly doubled.     

Components of Banisteriopsis caapi,a Plant Used in the Preparation of the Psychoactive Ayahuasca,Induce Anti-Inflammatory Effects in Microglial Cells

Banisteriopsis caapi is used to prepare the psychoactive beverage ayahuasca, and both have therapeutic potential for the treatment of many central nervous system (CNS) conditions. This study aimed to isolate new bioactive compounds from B. caapi extract and evaluate their biological activity, and that of the known β-carboline components of the plant (harmine, harmaline, and tetrahydroharmine), in BV-2 microglial cells, the in vivo activation of which is implicated in the physiopathology of CNS disorders. B. caapi extract was fractionated using semipreparative liquid chromatography (HPLC-DAD) and the exact masses ([M + H]⁺ m/z) of the compounds in the 5 isolated fractions were determined by high-resolution LC-MS/MS: F1 (174.0918 and 233.1289), F2 (353.1722), F3 (304.3001), F4 (188.1081), and F5 (205.0785). Harmine (75.5–302 µM) significantly decreased cell viability after 2 h of treatment and increased the number of necrotic cells and production of reactive oxygen species at equal or lower concentrations after 24 h. F4 did not impact viability but was also cytotoxic after 24 h. Most treatments reduced proinflammatory cytokine production (IL-2, IL-6, IL-17, and/or TNF), especially harmaline and F5 at 2.5 µM and higher concentrations, tetrahydroharmine (9.3 µM and higher), and F5 (10.7 µM and higher). The results suggest that the compounds found in B. caapi extract have anti-inflammatory potential that could be explored for the development of treatments for neurodegenerative diseases.     

Host–guest inter­action in a thio­urea–dimethyl oxalate (2/1) complex at 300 and 100 K

The title complex, 2CH₄N₂S·C₄H₆O₄, is a host–guest system. The asymmetric unit consists of one complete thio­urea mol­ecule and one‐half of a dimethyl oxalate mol­ecule lying on an inversion centre. The host thio­urea mol­ecules are connected to form zigzag chains by N—H⋯S hydrogen bonds. The guest dimethyl oxalate mol­ecules provide O‐atom acceptors for N—H⋯O hydrogen bonds, thus inter­connecting the chains of thio­urea mol­ecules to form completely connected sheets. The reduction in temperature from 300 to 100 K leaves the structure unchanged and still isostructural with that previously determined for the analogous thio­urea–diethyl oxalate (2/1) complex. It does, however, induce closer packing of the mol­ecules, general shrinkage of the unit cell and shortening of the hydrogen bonds, these last two to the extent of 1–2%.     

Microbial transformation of laxogenin by the fungus Syncephalastrum racemosum

Biotransformation of laxogenin (LG, 1) was performed by the fungus Syncephalastrum racemosum (AS 3.264). Thirteen previously undescribed metabolites were obtained and their structures were elucidated by spectroscopic analysis. S. racemosum catalyzes mainly oxygenation reactions of the B, C, and D rings of the sapogenin to afford metabolites 2–12. Conversion of the spirostanol skeleton to cholestane-type was also encountered in metabolite 13. Rearrangement of F-ring afforded F-ring ‘furanose’ sapogenin was observed in metabolite 14. The substrate and its derivatives were evaluated for their anti-neuroinflammatory activities. LG and metabolites 2, 3, 5, 8–10 and 13–14 exhibited moderate to good inhibitory activities on lipopolysaccharide-induced NO (nitric oxide) production in BV-2?cells. Moreover, 1, 2 and 5 dose-dependently reduced the LPS-induced iNOS and COX-2 expressions.     

Photocatalytic Degradation of Palm Oil Mill Effluent (POME) Waste Using BiVO4 Based Catalysts

Disposal of palm oil mill effluent (POME), which is highly polluting from the palm oil industry, needs to be handled properly to minimize the harmful impact on the surrounding environment. Photocatalytic technology is one of the advanced technologies that can be developed due to its low operating costs, as well as being sustainable, renewable, and environmentally friendly. This paper reports on the photocatalytic degradation of palm oil mill effluent (POME) using a BiVO₄ photocatalyst under UV-visible light irradiation. BiVO₄ photocatalysts were synthesized via sol-gel method and their physical and chemical properties were characterized using several characterization tools including X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), surface area analysis using the BET method, Raman spectroscopy, electron paramagnetic resonance (EPR), and UV-Vis diffuse reflectance spectroscopy (UV-Vis DRS). The effect of calcination temperature on the properties and photocatalytic performance for POME degradation using BiVO₄ photocatalyst was also studied. XRD characterization data show a phase transformation of BiVO₄ from tetragonal to monoclinic phase at a temperature of 450 °C (BV-450). The defect site comprising of vanadium vacancy (V_v) was generated through calcination under air and maxima at the BV-450 sample and proposed as the origin of the highest reaction rate constant (k) of photocatalytic POME removal among various calcination temperature treatments with a k value of 1.04 × 10⁻³ min⁻¹. These findings provide design guidelines to develop efficient BiVO₄-based photocatalyst through defect engineering for potential scalable photocatalytic organic pollutant degradation.     

Cytotoxic and Anti-Inflammatory Activities of Dihydroisocoumarin and Xanthone Derivatives from Garcinia picrorhiza

Garcinia picrorhiza, a woody plant native to Sulawesi and Maluku Islands, Indonesia, has been traditionally used as a wound healing ointment. In our continuous search for bioactive compounds from this plant, 15 phenolic compounds were isolated from its stem bark, including a previously undescribed dihydroisocoumarin, 2′-hydroxyannulatomarin, and two undescribed furanoxanthones, gerontoxanthone C hydrate and 3′-hydroxycalothorexanthone. The structures of the new metabolites were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR and HRESIMS. Gerontoxanthone C hydrate possessed cytotoxicity against four cancer cells (KB, HeLa S3, MCF-7, and Hep G2) with IC₅₀ values ranging from 5.6 to 7.5 µM. Investigation on the anti-inflammatory activities showed that 3′-hydroxycalothorexanthone inhibited NO production in RAW 264.7 and BV-2 cell lines with IC₅₀ values of 16.4 and 13.8 µM, respectively, whereas only (−)-annulatomarin possessed inhibition activity on COX-2 enzyme over 10% at 20 µM. This work describes the presence of 3,4-dihydroisocoumarin structures with a phenyl ring substituent at C-3, which are reported the first time in genus Garcinia. These findings also suggest the potential of furanxanthone derivatives as cytotoxic and anti-inflammatory agents for further pharmacological studies.     

2′‐Hydroxy‐4′′‐dimethylaminochalcone

The title compound, 3‐[4‐(di­methyl­amino)­phenyl]‐1‐(2‐hydroxy­phenyl)­prop‐2‐en‐1‐one, C₁₇H₁₇NO₂, is a chalcone derivative substituted by 2′‐hydroxyl and 4′′‐di­methyl­amino groups. The crystal structure indicates that the aniline and hydroxy­phenyl groups are nearly coplanar, with a dihedral angle of 10.32 (16)° between their phenyl rings. The molecular planarity of this substituted chalcone is strongly affected by the 2′‐hydroxyl group.     

Unexpected dipivaloyl­ation of 9‐li­thia­ted fluorene: formation of 1‐(fluoren‐9‐yl­idene)‐2,2‐di­methyl­propyl pivalate

Treatment of 9‐li­thia­ted fluorene with pivaloyl chloride provided ap‐9‐pivaloyl­fluorene, (1), the major product, and a minor product ultimately identified as the title compound, C₂₃H₂₆O₂, (2). The latter was also formed directly, but slowly, from 9‐li­thia­ted‐(1) treated with pivaloyl chloride. Although (1) exists exclusively as its less sterically restricted ap rotamer, its sp²‐hybridized anion sterically impedes reaction at the 9‐position from either face. While 9‐li­thia­ted‐(1) is exclusively, but slowly, 9‐methyl­ated with methyl iodide, reaction with pivaloyl chloride, also slow, leads only to the O‐acyl­ated product, (2). The protons of the tert‐butyl‐C=C moiety approach a proton on the fluorene ring to well within the sum of their van der Waals radii, resulting in significant molecular compression, strain and distortion. For example, distortion in the moiety C=C(O)(C) is exhibited by the enlargement of C=C—C angle to 130.6 (2)° at the expense of the corresponding `equivalent' C=C—O angle, which is compressed to 116.46 (19)°.     

Saponins from the roots of Chenopodium bonus-henricus L.

Two new glycosides of phytolaccagenin and 2β-hydroxyoleanoic acid, namely bonushenricoside A (3) and bonushenricoside B (5) together with four known saponins, respectively compounds 3-O-L-α-arabinopyranosyl-bayogenin-28-O-β-glucopyranosyl ester (1), 3-O-β-glucuronopyranosyl-2β-hydroxygypsogenin-28-O-β-glucopyranosyl ester (2), 3-O-β-glucuronopyranosyl-bayogenin-28-O-β-glucopyranosyl ester (4) and 3-O-β-glucuronopyranosyl-medicagenic acid-28-β-xylopyranosyl(1→4)-α-rhamnopyranosyl(1→2)-α-arabinopyranosyl ester (6) were isolated from the roots of Chenopodium bonus-henricus L. The structures of the compounds were determined by means of spectroscopic methods (1D and 2D NMR, IR and HRMS). The MeOH extract and compounds were tested for cytotoxic activity on five leukemic cell lines (HL-60, SKW-3, Jurkat E6-1, BV-173 and K-562). In addition, the ability of metanolic extract and saponins to modulate the interleukin-2 production in PHA/PMA stimulated Jurkat E6-1 cells was investigated as well.     

Phase transitions in n-alkyl­ammonium di­hydrogenphosphates and -arsenates and ferroelastic n-hexyl- and n-octyl­ammonium di­hydrogen­arsenate

-Hexyl­ammonium di­hydrogenarsenate, (C₆­H₁₆N)[AsO₂(OH)₂], and -octyl­ammonium di­hydrogenarsenate, (C₈H₂₀N)[AsO₂(OH)₂], are both ferroelastic at room temperature. The samples used in this study were not subjected to a phase transition after they had been crystallized. The structures are monoclinic (P2₁/n) and isostructural with the corresponding di­hydrogenphosphates. Each sample contained two domains and each structure was refined as a twin. There are strong hydrogen bonds between di­hydrogenarsenates and moderate hydrogen bonds between di­hydrogenarsenates and -alkyl­ammonium groups. The hydrogen-bond distances correspond well to those observed in the di­hydrogenphosphates. All the atoms except two H atoms exist in pairs linked by the lost symmetry operations derived from the prototypic space group P2/b2₁/n2₁/a. Each of these two different H atoms is involved in an asymmetric hydrogen bond between an oxy­gen pair. These oxy­gens are supposed to change their roles as hydrogen-bond donors and acceptors during the ferroelastic switching. The phase-transition sequences are affected by interactions between the neighbouring organic chains in the structure.