Curcuma sp.-derived dehydrocurdione induces heme oxygenase-1 through a Michael reaction between its α, ß-unsaturated carbonyl and Keap1.

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.

Bioproduction of Cinchona alkaloids by the endophytic fungus Diaporthe sp. associated with Cinchona ledgeriana.

We report that an endophytic filamentous fungus species of the genus Diaporthe isolated from Cinchona ledgeriana (Rubiaceae) produces Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) upon cultivation in a synthetic liquid medium. This study provides evidence that Cinchona alkaloids are produced not only in Cinchona plant cells, but also in the endophytic microbe cells, and will help to elucidate the relationship between endophytic microbes and their host plants.

Cinchona alkaloids are also produced by an endophytic filamentous fungus living in cinchona plant.

We report that the endophytic filamentous fungus Diaporthe sp., isolated from Cinchona ledgeriana and cultivated in a synthetic liquid medium, produces Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine). This shows that Cinchona alkaloids are produced not only in Cinchona plant cells, but also in endophytic microbe cells.

Microbial conversion of curcumin into colorless hydroderivatives by the endophytic fungus Diaporthe sp. associated with Curcuma longa.

We investigated the microbial conversion of curcumin (1) using endophytic fungi associated with the rhizome of Curcuma longa (Zingiberaceae). We found that Diaporthe sp., an endophytic filamentous fungus, converts curcumin (1) into four colorless derivatives, namely (3R,5R)-tetrahydrocurcumin (2), a novel (3R,5S)-hexahydrocurcumin (3) named neohexahydrocurcumin, (3S,5S)-octahydrocurcumin (4) and meso-octahydrocurcumin (5).

High ophiobolin A production in endophytic fungus Bipolaris sp. associated with Datura metel.

Ophiobolin A, a metabolite of fungi, is known to induce cell death and have anticancer activity. Therefore, obtaining ophiobolin A has become an important aspect in studying activity with medicinal properties that are affected by it. Ophiobolin A-producing filamentous fungi are endophytic or infectious microbes that attack annual and short-cycle plants. Here we isolated the endophyte of Datura metel, which is an annual plant that produces ophiobolin A. Results of this study have led to the identification of an endophytic filamentous fungus Bipolaris sp. with high ophiobolin A production (235 mg/L) in liquid culture after 21 days. Our findings further indicate that ophiobolin A-producing fungi live in short-cycle plants, and a method of finding the fungus is described.

Composition of the endophytic filamentous fungi associated with Cinchona ledgeriana seeds and production of Cinchona alkaloids.

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.

Ability of endophytic filamentous fungi associated with Cinchona ledgeriana to produce Cinchona alkaloids.

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.

Artemisioside, a new monoterpene glucoside from the aerial parts of Artemisia ordosica (Asteraceae).

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.

Transformation of Cinchona alkaloids into 1-N-oxide derivatives by endophytic Xylaria sp isolated from Cinchona pubescens.

The microbial transformation of four Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) by endophytic fungi isolated from Cinchona pubescens was investigated. The endophytic filamentous fungus Xylaria sp. was found to transform the Cinchona alkaloids into their 1-N-oxide derivatives.