211 research outputs found

    The macrocyclic lactone oxacyclododecindione reduces fibrosis progression

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    Background: Renal fibrosis is one of the most important triggers of chronic kidney disease (CKD), and only a very limited number of therapeutic options are available to stop fibrosis progression. As fibrosis is characterized by inflammation, myofibroblast activation, and extracellular matrix (ECM) deposition, a drug that can address all these processes might be an interesting therapeutic option.Methods: We tested in vivo in an ischemia‚Äďreperfusion (I/R) model in C57BL/6 mice and in kidney tubular epithelial cells (TEC) (HK2 cell line and primary cells) whether the natural product oxacyclododecindione (Oxa) reduces fibrosis progression in kidney disease. This was evaluated by Western blot, mRNA expression, and mass spectrometry secretome analyses, as well as by immunohistochemistry.Results: Indeed, Oxa blocked the expression of epithelial‚Äďmesenchymal transition marker proteins and reduced renal damage, immune cell infiltration, and collagen expression and deposition, both in vivo and in vitro. Remarkably, the beneficial effects of Oxa were also detected when the natural product was administered at a time point of established fibrotic changes, a situation close to the clinical situation. Initial in vitro experiments demonstrated that a synthetic Oxa derivative possesses similar features.Conclusion: Although open questions such as possible side effects need to be investigated, our results indicate that the combination of anti-inflammatory and anti-fibrotic effects of Oxa make the substance a promising candidate for a new therapeutic approach in fibrosis treatment, and thus in the prevention of kidney disease progression

    An In Vitro Study of Local Oxygen Therapy as Adjunctive Antimicrobial Therapeutic Option for Patients with Periodontitis

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    Periodontitis is a common global disease caused by bacterial dysbiosis leading to tissue destruction, and it is strongly associated with anaerobic bacterial colonization. Therapeutic strategies such as oxygen therapy have been developed to positively influence the dysbiotic microbiota, and the use of oxygen-releasing substances may offer an added benefit of avoiding systemic effects commonly associated with antibiotics taken orally or hyperbaric oxygen therapy. Therefore, the oxygen release of calcium peroxide (CaO2) was measured using a dissolved oxygen meter, and CaO2 solutions were prepared by dissolving autoclaved CaO2 in sterile filtered and deionized water. The effects of CaO2 on planktonic bacterial growth and metabolic activity, as well as on biofilms of Streptococcus oralis and Porphyromonas gingivalis, were investigated through experiments conducted under anaerobic conditions. The objective of this study was to investigate the potential of CaO2 as an antimicrobial agent for the treatment of periodontitis. Results showed that CaO2 selectively inhibited the growth and viability of P. gingivalis (p S. oralis (p 2 has the potential to selectively affect both planktonic bacteria and mono-species biofilms of P. gingivalis. The results of this study suggest that CaO2 could be a promising antimicrobial agent with selective activity for the treatment of periodontitis

    Total Synthesis and Biological Evaluation of the Anti-Inflammatory (13<i>R</i>,14<i>S</i>,15<i>R</i>)‚ÄĎ13-Hydroxy-14-deoxyoxacyclododecindione

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    The first total synthesis of the natural product (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclo­dodecindione, which was isolated in 2018 as a member of the oxacyclo­dodecindione family, is reported. A synthetic strategy through intramolecular Friedel-Crafts acylation combined with the stereoselective synthesis of a new triol key fragment allowed the preparation of the macrolactone. Due to mismatching physical data of the synthetic product, a revision of the configuration of the natural product isolated in 2018 is required. Light-induced E/Z-isomerism of the macrolactone backbone is described for the first time in the class of oxacyclo­dodecindione-type macrolactones. The hydroxylated macrolactone prepared herein was found to show highly promising IC50 values in biological assays addressing the inhibition of inflammatory responses

    Total Synthesis and Biological Evaluation of the Anti-Inflammatory (13<i>R</i>,14<i>S</i>,15<i>R</i>)‚ÄĎ13-Hydroxy-14-deoxyoxacyclododecindione

    No full text
    The first total synthesis of the natural product (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclo­dodecindione, which was isolated in 2018 as a member of the oxacyclo­dodecindione family, is reported. A synthetic strategy through intramolecular Friedel-Crafts acylation combined with the stereoselective synthesis of a new triol key fragment allowed the preparation of the macrolactone. Due to mismatching physical data of the synthetic product, a revision of the configuration of the natural product isolated in 2018 is required. Light-induced E/Z-isomerism of the macrolactone backbone is described for the first time in the class of oxacyclo­dodecindione-type macrolactones. The hydroxylated macrolactone prepared herein was found to show highly promising IC50 values in biological assays addressing the inhibition of inflammatory responses

    Total Synthesis and Biological Evaluation of the Anti-Inflammatory (13<i>R</i>,14<i>S</i>,15<i>R</i>)‚ÄĎ13-Hydroxy-14-deoxyoxacyclododecindione

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    The first total synthesis of the natural product (13R,14S,15R)-13-hydroxy-14-deoxyoxacyclo­dodecindione, which was isolated in 2018 as a member of the oxacyclo­dodecindione family, is reported. A synthetic strategy through intramolecular Friedel-Crafts acylation combined with the stereoselective synthesis of a new triol key fragment allowed the preparation of the macrolactone. Due to mismatching physical data of the synthetic product, a revision of the configuration of the natural product isolated in 2018 is required. Light-induced E/Z-isomerism of the macrolactone backbone is described for the first time in the class of oxacyclo­dodecindione-type macrolactones. The hydroxylated macrolactone prepared herein was found to show highly promising IC50 values in biological assays addressing the inhibition of inflammatory responses

    Ethyl Hydroxyethyl Cellulose&mdash;A Biocompatible Polymer Carrier in Blood

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    The biocompatibility of carrier nanomaterials in blood is largely hampered by their activating or inhibiting role on the clotting system, which in many cases prevents safe intravascular application. Here, we characterized an aqueous colloidal ethyl hydroxyethyl cellulose (EHEC) solution and tested its effect on ex vivo clot formation, platelet aggregation, and activation by thromboelastometry, aggregometry, and flow cytometry. We compared the impact of EHEC solution on platelet aggregation with biocompatible materials used in transfusion medicine (the plasma expanders gelatin polysuccinate and hydroxyethyl starch). We demonstrate that the EHEC solution, in contrast to commercial products exhibiting Newtonian flow behavior, resembles the shear-thinning behavior of human blood. Similar to established nanomaterials that are considered biocompatible when added to blood, the EHEC exposure of resting platelets in platelet-rich plasma does not enhance tissue thromboplastin- or ellagic acid-induced blood clotting, or platelet aggregation or activation, as measured by integrin &alpha;IIb&beta;3 activation and P-selectin exposure. Furthermore, the addition of EHEC solution to adenosine diphosphate (ADP)-stimulated platelet-rich plasma does not affect the platelet aggregation induced by this agonist. Overall, our results suggest that EHEC may be suitable as a biocompatible carrier material in blood circulation and for applications in flow-dependent diagnostics

    Antimicrobial Activity of <i>Eucalyptus globulus</i>, <i>Azadirachta indica</i>, <i>Glycyrrhiza glabra</i>, <i>Rheum palmatum</i> Extracts and Rhein against <i>Porphyromonas gingivalis</i>

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    Novel plant-derived antimicrobials are of interest in dentistry, especially in the treatment of periodontitis, since the use of established substances is associated with side effects and concerns of antimicrobial resistance have been raised. Thus, the present study was performed to quantify the antimicrobial efficacy of crude plant extracts against Porphyromonas gingivalis, a pathogen associated with periodontitis. The minimal inhibitory concentrations (MICs) of Eucalyptus globulus leaf, Azadirachta indica leaf, Glycyrrhiza glabra root and Rheum palmatum root extracts were determined by broth microdilution for P. gingivalis ATCC 33277 according to CLSI (Clinical and Laboratory Standards Institute). The MICs for the E. globulus, A. indica and G. glabra extracts ranged from 64 mg/L to 1024 mg/L. The lowest MIC was determined for an ethanolic R. palmatum extract with 4 mg/L. The MIC for the anthraquinone rhein was also measured, as the antimicrobial activity of P. palmatum root extracts can be partially traced back to rhein. Rhein showed a remarkably low MIC of 0.125 mg/L. However, the major compounds of the R. palmatum root extract were not further separated and purified. In conclusion, R. palmatum root extracts should be further studied for the treatment of periodontitis

    Drug Candidates for Autoimmune Diseases

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    Most of the immunosuppressive drugs used in the clinic to prevent organ rejection or to treat autoimmune disorders were originally isolated from fungi or bacteria. Therefore, in addition to plants, these are valuable sources for identification of new potent drugs. Many side effects of established drugs limit their usage and make the identification of new immunosuppressants necessary. In this review, we present a comprehensive overview of natural products with potent anti-inflammatory activities that have been tested successfully in different models of chronic inflammatory autoimmune diseases. Some of these candidates already have passed first clinical trials. The anti-inflammatory potency of these natural products was often comparable to those of established drugs, and they could be used at least in addition to standard therapy to reduce their dose to minimize unwanted side effects. A frequent mode of action is the inhibition of classical inflammatory signaling pathways, such as NF-őļB, in combination with downregulation of oxidative stress. A drawback for the therapeutic use of those natural products is their moderate bioavailability, which can be optimized by chemical modifications and, in addition, further safety studies are necessary. Altogether, very interesting candidate compounds exist which have the potential to serve as starting points for the development of new immunosuppressive drugs

    The ADEBAR project: European and international provision of analytical data from structure elucidation and analytical characterization of NPS.

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    Novel substances for which none or limited analytical data are available constitute a challenge for police and customs forensic laboratories. The time-consuming process of structural elucidation and acquisition of analytical data has been centralized in the ADEBAR project in Germany, co-funded since 2017 by the EU's Internal Security Fund. The project aims to comprehensively characterize substances relevant for forensic-toxicological casework within the analytical competence network. The analytical datasets are distributed digitally through European and (inter)national channels. Additionally, pharmacological evaluation allows for estimating in vivo potency and potential harm required as scientific evidence for legislative amendments. The ADEBAR project contributes to the availability of analytical data on new substances relevant to the daily work of police and customs laboratories. Since the inception of the ADEBAR project, 549 samples have been registered, and 302 substance reports notified to the EMCDDA, including numerous spectrometric and spectroscopic data. In addition, 3,619 mass spectra have been accumulated in ADEBAR mass spectra databases. A central institution for the structure elucidation and acquisition of valid, high-quality analytical data for police and customs forensic laboratories and forensic medicine institutes is important in the future because there does not seem to be an end to the dynamic of novel NPS appearing on the drug market
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