Lignan Derivatives from Krameria lappacea Roots Inhibit Acute Inflammation in Vivo and Pro-inflammatory Mediators in Vitro

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (111) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID50 77 \u3bcg/cm2) as well compounds 111 (ID50 0.310.60 \u3bcmol/cm2) exhibited topical antiedematous properties comparable to those of indomethacin (ID50 0.29 \u3bcmol/cm2) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NFkB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E2 synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug

Plant extracts in cell-based anti-inflammatory assays—Pitfalls and considerations related to removal of activity masking bulk components

Plants used in traditional medicine represent an important source of new lead compounds. However, cell-based in vitro screening assays with plant material are hampered by the complex nature of plant extracts as mixtures of active and inactive components. Bulk constituents, such as chlorophyll and polyphenols were previously shown to interfere with several biological in vitro assays. Their influence on anti-inflammatory cell-based testing systems has not been thoroughly investigated. Hence, the present study was aimed at comparing different procedures for the removal of bulk constituents from plant extracts and examining the influence of their elimination on selected cell-based anti-inflammatory assays. Malva sp. and Glechoma hederacea L., two plants used in traditional European medicine for the treatment of inflammatory disorders, were subjected to three different methods for the removal of chlorophyll and polyphenols, respectively. Removal of bulk constituents was confirmed by HPLC and mass spectrometry. Extracts were tested before and after the purification procedure, to determine their potential to inhibit the activation of the transcription factor NF-κB in reporter gene assay and to interfere with the secretion of the chemokine IL-8 after stimulation of endothelial cells with tumor necrosis factor (TNF-α) or lipopolysaccharide (LPS). Removal of chlorophyll from tested extracts led to a strong decrease in the anti-inflammatory activities, due to loss of bioactive constituents. In contrast, the effect of the polyphenol-free extracts was either not changed or significantly increased, depending on the purification method used. The study concluded that clearance of bulk compounds represents a valuable strategy for cell-based in vitro anti-inflammatory evaluation of plant extracts. Liquid–liquid partitioning was identified as the optimal method for the elimination of both chlorophyll and polyphenols. It is recommended that removal of chlorophyll from extracts always be accompanied by HPLC profiling to detect a possible loss of active constituents

Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease

Background: The major histocompatibility complex (MHC) is the most important genomic region that contributes to the risk of graft versus host disease (GVHD) after haematopoietic stem cell transplantation. Matching of MHC class I and II genes is essential for the success of transplantation. However, the MHC contains additional genes that also contribute to the risk of developing acute GVHD. It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes and other genes involved in the pathophysiology of GVHD by mRNA expression profiling. Methodology/Principal Findings: To reduce the complexity of the task, we used genetically well-defined rat inbred strains and a rat skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR), to analyze the expression of MHC, natural killer complex (NKC), and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 MHC, 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected MHC and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in GVHD-affected skin lesions of transplanted rats and in human skin explant assays. Conclusions/Significance: We identified rat and human MHC and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for GVHD. Several of the respective human genes, including HLA-DMB, C2, AIF1, SPR1, UBD, and OLR1, are polymorphic. These candidates may therefore contribute to the genetic risk of GVHD in patients

A virtual screening approach for identifying plants with anti H5N1 neuraminidase activity

Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here, we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 μM. Furthermore, four of the 12 isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources

A sketch on aquisition by higher cognitive concepts

SIGLEDEGerman

Ein logik-orientierter Ansatz zum automatischen Text-verstehen

Engl. Version erscheint in L.Bolc: Natural based computer systems. Dieser Bericht loest Nr. 3/77 inhaltlich abSIGLETIB: AC 6074 (1979,1),2 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische Informationsbibliothek2. ed..DEGerman

Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 by plant extracts used as traditional antidiabetic medicines

Elevated glucocorticoids are a key risk factor for metabolic diseases, and the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) represents a promising therapeutic target. We measured the potential of six traditional antidiabetic medicinal plants extracts to inhibit 11beta-HSD1 activity and glucocorticoid receptor (GR) activation in transfected HEK-293 cells. Leave extracts of Eriobotrya japonica preferentially inhibited 11beta-HSD1 over 11beta-HSD2. Extracts of roasted but not native coffee beans preferentially inhibited 11beta-HSD1 over 11beta-HSD2, emphasizing the importance of sample preparation. Thus, natural compounds inhibiting 11beta-HSD1 may contribute to the antidiabetic effect of the investigated plant extracts