Screening of Vietnamese medicinal plants for NF-κB signaling inhibitors: Assessing the activity of flavonoids from the stem bark of Oroxylum indicum

AbstractEthnopharmacological relevanceSeventeen plants used in Vietnamese traditional medicine for the treatment of inflammatory disorders were screened for NF-κB inhibitory activity. Oroxylum indicum, which exhibited activity, was investigated in detail.Materials and methodsForty plant extracts from 17 species were prepared by maceration using dichloromethane and methanol and were tested (10µg/mL) to evaluate their ability to inhibit NF-κB activation using TNF-α-stimulated HEK-293 cells stably transfected with a NF-κB-driven luciferase reporter. The active extract of Oroxylum indicum was subsequently fractionated by different chromatographic techniques. After isolation, all single compounds were identified by spectroscopic methods and assessed for NF-κB inhibitory effects.ResultsThe dichloromethane extracts obtained from Chromolaena odorata leaves and the stem bark of Oroxylum indicum showed distinct inhibitory effects on NF-κB activation at a concentration of 10µg/mL. The active extract of Oroxylum indicum was subjected to further phytochemical studies resulting in identification of four flavonoid aglyca and six flavonoid glycosides. Pharmacological evaluation of the obtained compounds identified oroxylin A as the most active substance (IC50=3.9µM, 95% CI: 3.5–4.4µM), while chrysin and hispidulin showed lower activity with IC50=7.2µM (95% CI: 6.0–8.8µM) and 9.0µM (95% CI: 7.9–10.2µM), respectively. Interestingly, in this study the activity of baicalein (IC50=28.1µM, 95% CI: 24.6–32.0µM) was weak. The isolated glycosides showed no inhibitory activity when tested at a concentration of 30µM. Quantification of the four active flavonoids in extracts and plant materials suggested that oroxylin A contributes to the NF-κB inhibitory activity of the stem barks of Oroxylum indicum to a greater extent than baicalein which was thought to be responsible for the anti-inflammatory activity of this plant.ConclusionsThe screening presented in this study identified the dichloromethane extracts of Chromolaena odorata and Oroxylum indicum as promising sources for NF-κB inhibitors. Hispidulin, baicalein, chrysin and oroxylin A, isolated from Oroxylum indicum, were identified as inhibitors of NF- κB activation

EuProGigant – A Concept Towards an Industrial System Architecture for Data-Driven Production Systems

Today, most IoT solutions for the production ecosystem stem from trends that first established at the consumer market. Although these concepts have been adapted well in the industrial environment, it led to fragmented solutions that require complex interfaces. With the recent introduction of GAIA-X, it becomes possible to develop platform independent IoT solutions tailored to the needs of manufacturers. Until now, GAIA-X is only a concept proposed by governments and economic advisory boards. This paper extends the concept into an industrial system architecture that enables the reliable exchange of information among the supply chain of a highly distributed production network

Anwendungen und Geschäftsmodelle mit Gaia-X

Derzeit entwickelt eine Vielzahl von geförderten Konsortien Anwendungsfälle im Gaia-X-Kontext. Sie sind charakterisiert durch den Nutzen des unternehmensübergreifenden Datenaustauschs. Dennoch wird ein Großteil der Vorhaben keiner bewussten Kosten-Nutzen-Analyse unterzogen. Bestehende Vorgehensmodelle für datenbasierte Geschäftsmodelle berücksichtigen die Interoperabilität nicht. Es fehlt eine ganzheitliche Beschreibung, wie Anwendungsfälle in wettbewerbsfähige Geschäftsmodelle überführt werden

Eurycomalactone Inhibits Expression of Endothelial Adhesion Molecules at a Post-Transcriptional Level

The C-19 quassinoid eurycomalactone (<b>1</b>) has recently been shown to be a potent (IC₅₀ = 0.5 μM) NF-κB inhibitor in a luciferase reporter model. In this study, we show that <b>1</b> with similar potency inhibited the expression of the NF-κB-dependent target genes ICAM-1, VCAM-1, and E-selectin in TNFα-activated human endothelial cells (HUVECtert) by flow cytometry experiments. Surprisingly, <b>1</b> (2 μM) did not inhibit TNFα-induced IKKα/β or IκBα phosphorylation significantly. Also, the TNFα-induced degradation of IκBα remained unchanged in response to <b>1</b> (2 μM). In addition, pretreatment of HUVECtert with <b>1</b> (2 μM) had no statistically significant effect on TNFα-mediated nuclear translocation of the NF-κB subunit p65 (RelA). Quantitative RT-PCR revealed that <b>1</b> (0.5–5 μM) exhibited diverse effects on the TNFα-induced transcription of <i>ICAM-1</i>, <i>VCAM-1</i>, and <i>SELE</i> genes since the mRNA level either remained unchanged (ICAM-1, E-selectin, and VCAM-1 at 0.5 μM <b>1</b>), was reduced (VCAM-1 at 5 μM <b>1</b>), or even increased (E-selectin at 5 μM <b>1</b>). Finally, the time-dependent depletion of a short-lived protein (cyclin D1) as well as the measurement of <i>de novo</i> protein synthesis in the presence of <b>1</b> (2–5 μM) suggested that <b>1</b> might act as a protein synthesis inhibitor rather than an inhibitor of early NF-κB signaling

Long-term trends in the prescription of antidiabetic drugs: real-world evidence from the Diabetes Registry Tyrol 2012–2018

Introduction Prescription patterns of antidiabetic drugs in the period from 2012 to 2018 were investigated based on the Diabetes Registry Tyrol. To validate the findings, we compared the numbers with trends of different national registries conducted in a comparable period of time.Research design and methods Medication data, prescription patterns, age groups, antidiabetic therapies and quality parameters (hemoglobin A1c, body mass index, complications) of 10 875 patients with type 2 diabetes from 2012 to 2018 were retrospectively assessed and descriptively analyzed. The changes were assessed using a time series analysis with linear regression and prescription trends were plotted over time.Results Sodium/glucose cotransporter 2 inhibitors (SGLT-2i) showed a significant increase in prescription from 2012 to 2018 (p&lt;0.001), as well as metformin (p=0.002), gliptins (p=0.013) and glucagon-like peptide-1 agonists (GLP-1a) (p=0.017). Significant reduction in sulfonylurea prescriptions (p&lt;0.001) was observed. Metformin was the most frequently prescribed antidiabetic drug (51.3%), followed by insulin/analogs (34.6%), gliptins (28.2%), SGLT-2i (11.7%), sulfonylurea (9.1%), glitazones (3.7%), GLP-1a (2.8%) and glucosidase inhibitors (0.4%).Conclusions In this long-term, real-world study on prescription changes in the Diabetes Registry Tyrol, we observed significant increase in SGLT-2i, metformin, gliptins and GLP-1a prescriptions. In contrast prescriptions for sulfonylureas declined significantly. Changes were consistent over the years 2012–2018. Changes in prescription patterns occurred even before the publication of international and national guidelines. Thus, physicians change their prescription practice not only based on published guidelines, but even earlier on publication of cardiovascular outcome trials

Identification of Chromomoric Acid C‑I as an Nrf2 Activator in <i>Chromolaena odorata</i>

Activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) contributes to several beneficial bioactivities of natural products, including induction of an increased cellular stress resistance and prevention or resolution of inflammation. In this study, the potential of a crude leaf extract of <i>Chromolaena odorata</i>, traditionally used against inflammation and skin lesions, was examined for Nrf2 activation. Guided by an Nrf2-dependent luciferase reporter gene assay, the phytoprostane chromomoric acid C-I (<b>1</b>) was identified as a potent Nrf2 activator from <i>C. odorata</i> with a CD (concentration doubling the response of vehicle-treated cells) of 5.2 μM. When tested at 1–10 μM, <b>1</b> was able to induce the endogenous Nrf2 target gene heme oxygenase 1 (HO-1) in fibroblasts. Between 2 and 5 μM, compound <b>1</b> induced HO-1 in vascular smooth muscle cells (VSMC) and inhibited their proliferation in a HO-1-dependent manner, without eliciting signs of cytotoxicity