This study presents phytochemical characterization and biological evaluation of Origanum vulgare L. essential oil (OEO) formulated as polymeric micelles drug delivery systems as a possible non-invasive approach for the management of skin tags. GC-MS analysis of Romanian OEO revealed the identification and quantification of 43 volatile compounds (thymol and carvacrol being the main ones). The antioxidant activity was shown by four consecrated methods: CUPRAC, ABTS, ORAC and DPPH. OEO was incorporated by micellar solubilization into a binary hydrogel based on a Pluronic F 127/L 31 block-copolymers mixture. The pH, consistency, spreadability, particle size, polydispersity index and zeta potential of the OEO-loaded poloxamer-based binary hydrogel (OEO-PbH) were investigated. OEO-PbH was skin compatible in terms of pH and exhibited adequate spreadability and consistency. The minimal inhibitory concentrations of the tested OEO were similar to those obtained for the formulation, lower (2.5 µg/mL) for yeast and higher (40–80 µg/mL) for Gram-negative bacilli. As keratinocytes are among main components of skin tags, an in vitro evaluation was conducted in order to see the effect of the formulation against HaCaT human keratinocytes. OEO-PbH decreased HaCaT cells migration and proliferation and elicited a cytotoxic and pro-apoptotic effect in a dose- and time-dependent manner. No harmful effect on the viability of dendritic cells (DCs) was detected following the incubation with different concentrations (0–200 µg/mL) of the 5% formulation. Treatment in inflammatory DCs (+LPS) indicated a decrease in cytokine production of IL-6, TNF-α and IL-23 but no significant effect on IL-10 in any of the tested concentrations.
Permanent exposure to pathogens requires decisions toward tolerance or immunity as a prime task of dendritic cells. The molecular mechanisms preventing uncontrolled immune responses are not completely clear. We investigated the regulatory function of Ncf1, an organizing protein of NADPH oxidase, in the signaling cascade of Toll-like receptors. TLR9-stimulated spleen cells from both Ncf1-deficient and B10.Q mice with a point mutation in exon 8 of Ncf1 exhibited increased IL-12p70 secretion compared with controls. This finding was restricted to stimulatory CpG2216 and not induced by CpG2088. Because only CpG/TLR9-induced IL-12p70 was regulated by Ncf1, we used TRIF−/− and MyD88−/− cells to show that TLR9/MyD88 was primarily affected. Interestingly, additional experiments revealed that spleen cells from NOX2/gp91phox-deficient mice and the blocking of electron transfer by diphenylene iodonium had no influence on CpG-induced IL-12p70, confirming an NADPH oxidase-independent function of Ncf1. Finally, proving the in vivo relevance CpG adjuvant-guided OVA immunization resulted in a strong augmentation of IL-12p70-dependent Th1 IFN-γ response only in Ncf1-deficient mice. These data suggest for the first time an important role for Ncf1 in the fine tuning of the TLR9/MyD88 pathway in vitro and in vivo that is independent of its role as an activator of NOX2.
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