ABSTRACT
To elucidate the anti-inflammatory mechanism of Curcuma sp., we investigated whether dehydrocurdione, a sesquiterpene contained in Curcuma sp., induces heme oxygenase (HO)-1, an antioxidative enzyme, in RAW 264.7 macrophages. Dehydrocurdione was extracted from the rhizome of Curcuma sp., and its purity was verified by high performance liquid chromatography. Treatment with 10-100 µM dehydrocurdione transiently and concentration-dependently increased HO-1 mRNA and protein levels. Docking simulation suggested the presence of the Michael reaction between dehydrocurdione and Kelch-like ECH-associated protein (Keap)1 keeping nuclear factor-erythroid2-related-factor (Nrf)2, a transcription factor, in the cytoplasm. Nrf2 that was definitely free from Keap1 was detected in the nuclei after dehydrocurdione treatment. Subsequently, the HO-1 E2 enhancer, a target of Nrf2, was activated, resulting in HO-1 expression. Also, an investigation using 6-shogaol and 6-gingerol supported the concept that the α, ß-unsaturated carbonyl structure plays an important role in the interaction with Keap1. Dehydrocurdione suppressed lipopolysaccharide-induced NO release, a marker of inflammation. Clarification of the HO-1 synthesis increase mechanism revealed in this study will help contribute to the development of novel phytotherapeutic strategies against inflammation-associated diseases.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Curcuma/chemistry , Heme Oxygenase-1/metabolism , Sesquiterpenes/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/pharmacology , Cells, Cultured , Enzyme Induction/drug effects , HEK293 Cells , Heme Oxygenase-1/chemistry , Humans , Kelch-Like ECH-Associated Protein 1/metabolism , Macrophages/drug effects , Macrophages/metabolism , Mice , NF-E2-Related Factor 2/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Protein Binding/drug effects , Protein Carbonylation , Protein Interaction Domains and Motifs , Sesquiterpenes/isolation & purificationABSTRACT
Four kinds of endophytic filamentous fungi (code names: CLS-1, CLS-2, CLS-3, and CLS-4) associated with the seeds of Cinchona ledgeriana (Rubiaceae) from West Java, Indonesia, were isolated. All of the isolates were classified into Diaporthe spp. based on phylogenetic analysis of the nucleotide sequences of the internal transcribed spacers (ITS1 and ITS2) including the 5.8S ribosomal DNA region. All four of these endophytic fungi produce Cinchona alkaloids, mainly quinine and quinidine, in synthetic liquid medium.
Subject(s)
Ascomycota/metabolism , Cinchona Alkaloids/metabolism , Cinchona/microbiology , Endophytes/metabolism , Phylogeny , Seeds/microbiology , Ascomycota/classification , Ascomycota/isolation & purification , Base Sequence , Cinchona/chemistry , Endophytes/classification , Endophytes/isolation & purification , Indonesia , Quinidine/metabolism , Quinine/metabolism , Seeds/chemistry , Species SpecificityABSTRACT
We have investigated the ability of endophytic filamentous fungi associated with Cinchona ledgeriana (Rubiaceae) to produce Cinchona alkaloids on potato dextrose agar medium and in a synthetic liquid medium. It was found that all twenty-one endophytic fungi produce Cinchona alkaloids, despite their genetic differences.
Subject(s)
Cinchona Alkaloids/metabolism , Cinchona/microbiology , Fungi/metabolism , Fungi/physiology , Molecular StructureABSTRACT
A new monoterpene glucoside, artemisioside, was isolated from the aerial parts of Artemisia ordosica Krasch. (Asteraceae). The chemical structure was elucidated from physicochemical data and by the application of Klyne's rule.