The (Bio)chemical Base of Flower Colour in Bidens ferulifolia.

Bidens ferulifolia is a yellow flowering plant, originating from Mexico, which is increasingly popular as an ornamental plant. In the past few years, new colour combinations ranging from pure yellow over yellow-red, white-red, pure white and purple have emerged on the market. We analysed 16 Bidens ferulifolia genotypes to provide insight into the (bio)chemical base underlying the colour formation, which involves flavonoids, anthochlors and carotenoids. In all but purple and white genotypes, anthochlors were the prevalent pigments, primarily derivatives of okanin, a 6'-deoxychalcone carrying an unusual 2'3'4'-hydroxylation pattern in ring A. The presence of a cytochrome-P450-dependent monooxygenase introducing the additional hydroxyl group in position 3' of both isoliquiritigenin and butein was demonstrated for the first time. All genotypes accumulate considerable amounts of the flavone luteolin. Red and purple genotypes additionally accumulate cyanidin-type anthocyanins. Acyanic genotypes lack flavanone 3-hydroxylase and/or dihydroflavonol 4-reductase activity, which creates a bottleneck in the anthocyanin pathway. The carotenoid spectrum was analysed in two Bidens genotypes and showed strong variation between the two cultivars. In comparison to anthochlors, carotenoids were present in much lower concentrations. Carotenoid monoesters, as well as diesters, were determined for the first time in B. ferulifolia flower extracts.

Immunomodulatory Therapy of Inflammatory Liver Disease Using Selectin-Binding Glycopolymers.

Immunotherapies have the potential to significantly advance treatment of inflammatory disease and cancer, which are in large part driven by immune cells. Selectins control the first step in immune cell adhesion and extravasation, thereby guiding leukocyte trafficking to tissue lesions. We analyzed four different highly specific selectin-binding glycopolymers, based on linear poly(2-hydroxypropyl)-methacrylamide (PHPMA) polymers. These glycopolymers contain either the tetrasaccharide sialyl-LewisX (SLeX) or the individual carbohydrates fucose, galactose, and sialic acids mimicking the complex SLeX binding motive. The glycopolymers strongly bind to primary human macrophages, without activating them, and also to primary human blood leukocytes, but poorly to fibroblasts and endothelial cells in vitro. After intravenous injection in mice, all glycopolymers accumulated in the liver without causing hepatotoxicity. The glycosylated binder most potently targeted resident hepatic macrophages (Kupffer cells) and protected mice from acute toxic liver injury in the two different experimental models, carbon tetrachloride (CCl4) or Concanavalin A (ConA)-based hepatitis. Its sulfated counterpart, on the other hand, induced a decrease in infiltrating and resident macrophages, increased T helper cells, and aggravated immune-mediated liver injury. We demonstrate that, in the context of selectin-binding glycopolymers, minor modifications strongly impact leukocyte influx and macrophage activation, thereby ameliorating or aggravating liver inflammation depending on the underlying immunopathology. The nonsulfated random glycopolymer is a promising candidate for the treatment of inflammatory disease. The modulation of hepatic immune cells by selectin-binding glycopolymers might breach the immunosuppressive hepatic microenvironment and could improve efficacy of immunotherapies for inflammatory disease and cancer.

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats.

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29mg/kg) compared to λ-cyhalothrin (2.65mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations were less, with γ-cyhalothrin being 1.3- to 1.6-fold more potent than λ-cyhalothrin. These potency differences are consistent with the purity of the λ-isomer (approximately 43%) compared to the enriched isomer γ-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of behavioral effects.