Identification of an anti-inflammatory potential of Eriodictyon angustifolium compounds in human gingival fibroblasts.

Polyphenol-rich plant extracts have been shown to possess anti-inflammatory activity against oral pathogen-induced cytokine release in model systems of inflammation. Here, it was hypothesized that a flavanone-rich extract of E. angustifolium exhibits an anti-inflammatory potential against endotoxin-induced inflammatory response in human gingival fibroblasts (HGF-1). HGF-1 cells were stimulated with lipopolysaccharide from Porphyromonas gingivalis (pg-LPS) to release pro-inflammatory cytokines. Concentrations of interleukins IL-6 and IL-8 and macrophage chemoattractant protein-1 in the incubation media upon stimulation were determined by means of magnetic bead analysis. A crude ethanol/water extract of E. angustifolium (EE) was fractionated via gel permeation chromatography into a flavanone-rich fraction (FF) and an erionic acid-rich fraction (EF). Individual flavanones and erionic acids as well as EE, EF and FF were tested in the pg-LPS-stimulated HGF-1 cells for their anti-inflammatory potential. The E. angustifolium extract possessed anti-inflammatory potential in this model system, attenuating the pg-LPS-induced release of IL-6 by up to 52.0 ± 15.5%. Of the individual flavanones, eriodictyol and naringenin had the most pronounced effect. However, a mixture of the flavanones did not possess the same effect as the entire flavanoid fraction, indicating that other compounds may contribute to the anti-inflammatory potential of E. angustifolium. For the first time, an anti-inflammatory potential of E. angustifolium and containing erionic acids has been determined.

Rubemamine and Rubescenamine, Two Naturally Occurring N-Cinnamoyl Phenethylamines with Umami-Taste-Modulating Properties.

Sensory screening of a series of naturally occurring N-cinnamoyl derivatives of substituted phenethylamines revealed that rubemamine (9, from Chenopodium album) and rubescenamine (10, from Zanthoxylum rubsecens) elicit strong intrinsic umami taste in water at 50 and 10 ppm, respectively. Sensory tests in glutamate- and nucleotide-containing bases showed that the compounds influence the whole flavor profile of savory formulations. Both rubemamine (9) and rubescenamine (10) at 10-100 ppm dose-dependently positively modulated the umami taste of MSG (0.17-0.22%) up to threefold. Among the investigated amides, only rubemamine (9) and rubescenamine (10) are able to directly activate the TAS1R1-TAS1R3 umami taste receptor. Moreover, both compounds also synergistically modulated the activation of TAS1R1-TAS1R3 by MSG. Most remarkably, rubemamine (9) was able to further positively modulate the IMP-enhanced TAS1R1-TAS1R3 response to MSG ∼ 1.8-fold. Finally, armatamide (11), zanthosinamide (13), and dioxamine (14), which lack intrinsic umami taste in vivo and direct receptor response in vitro, also positively modulated receptor activation by MSG about twofold and the IMP-enhanced MSG-induced TAS1R1-TAS1R3 responses approximately by 50%. In sensory experiments, dioxamine (14) at 25 ppm in combination with 0.17% MSG exhibited a sensory equivalent to 0.37% MSG.

Capsaicin, nonivamide and trans-pellitorine decrease free fatty acid uptake without TRPV1 activation and increase acetyl-coenzyme A synthetase activity in Caco-2 cells.

Red pepper and its major pungent component, capsaicin, have been associated with hypolipidemic effects in rats, although mechanistic studies on the effects of capsaicin and/or structurally related compounds on lipid metabolism are scarce. In this work, the effects of capsaicin and its structural analog nonivamide, the aliphatic alkamide trans-pellitorine and vanillin as the basic structural element of all vanilloids on the mechanisms of intestinal fatty acid uptake in differentiated intestinal Caco-2 cells were studied. Capsaicin and nonivamide were found to reduce fatty acid uptake, with IC50 values of 0.49 µM and 1.08 µM, respectively. trans-Pellitorine was shown to reduce fatty acid uptake by 14.0±2.14% at 100 µM, whereas vanillin was not effective, indicating a pivotal role of the alkyl chain with the acid amide group in fatty acid uptake by Caco-2 cells. This effect was associated neither with the activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or the epithelial sodium channel (ENaC) nor with effects on paracellular transport or glucose uptake. However, acetyl-coenzyme A synthetase activity increased (p<0.05) in the presence of 10 µM capsaicin, nonivamide or trans-pellitorine, pointing to an increased fatty acid biosynthesis that might counteract the decreased fatty acid uptake.

Identification of bisprenylated benzoic acid derivatives from yerba santa (Eriodictyon ssp.) using sensory-guided fractionation.

Due to certain off-flavor problems and lacking bitter masking effects with Yerba Santa (Eriodictyon angustifolium and E. californicum) extracts, which are also described as bitter, herbal, medicinal, phenolic, or astringent, methanolic extracts were fractionated and evaluated for their taste properties using a high temperature liquid chromatography (HTLC)-based approach. The taste-guided fractionation led to the identification of a series of novel bisprenylated benzoic acids (erionic acids A (1), B (2), C (3), D (4), E (5), and F (6) and eriolic acids A (7), B (8), C (9), and D (10), respectively), along with the known flavonoids eriodictyol, homoeriodictyol, hesperetin, and chrysoeriol. The new compounds were isolated in larger amounts for characterization from Narrow Leaf Yerba Santa (E. angustifolium) and California Yerba Santa (E. californicum), respectively, using fast centrifugal partition chromatography (FCPC) and HTLC. The structures were elucidated using one and two-dimensional NMR spectroscopy and high resolution mass spectrometry (HR-MS). For E. californicum, data regarding seasonal and climatic variation of the eriolic acid contents and of the flavonoids were collected. The flavor properties of some of the isolated new compounds were evaluated; they showed strong off-flavor characteristics, such as bitter, astringent, phenolic, or woody, and may contribute to the sensory effects observed for crude Yerba Santa extracts. Erionic acid C (3) was not only able to increase the absolute bitterness but also to extinguish the bitter masking effect of homoeriodictyol in a caffeine solution.

Characterization of flavor modulating effects in complex mixtures via high temperature liquid chromatography.

The identification of flavor modulating compounds, for example, bitter masking or sweet enhancing compounds, in complex mixtures such as botanical extracts or food preparations is difficult and time- and work-intensive. To accelerate this process, an improved screening method was developed on the basis of the separation of complex matrixes by the so-called LC Taste setup and subsequent comparative sensory analysis. The eluent containing only water and ethanol was diluted with a basic tastant solution (500 mg L(-1) caffeine and 5% sucrose, respectively) and evaluated by a trained panel by duo comparison tests. This novel method was applied to the known flavor and taste modulating substances homoeriodictyol (1), sterubin (2), hesperetin (3), and lactisol (9) as well as to simple mixtures of homoeriodictyol (1), sterubin (2), and hesperetin (3). To evaluate the potential of the method for more complex matrixes, the protocol was applied to plant extracts from Yerba Santa (Eriodictyon californicum) and honeybush tea (Cyclopia intermedia). The flavor modulating activities reported for homoeriodictyol (1), sterubin (2), and hesperetin (3) could be confirmed in these complex mixtures.