Inducing secondary metabolite production from Daldinia eschscholzii JC-15 by red ginseng medium.

Red ginseng (RG) is one of the most popular herbal medicines and used as a dietary supplement in recent years. The bioactive ingredient in RG can induce the production of novel microbial metabolite from fermented RG. Using the one strain-many compounds strategy, the reinvestigation of the metabolites from Daldinia eschscholzii JC-15 cultured in red ginseng medium led to the isolation of an unprecedented benzopyran-naphthalene hybrid, daldinsin (1) and a new lactone (2). In this research, a new lactone, 8-hydroxylhelicascolide A (2) instead of helicascolide A was produced by the D. eschscholzii JC-15 induced by the red ginseng medium. Compound 1 showed anti-acetylcholinesterase activity with the inhibition ratio of 38.8% at 50 µM. Compound 2 indicated antimicrobial activities against Fusarium Solani, F. oxysporum, and Escherichia coli with MICs at 128 µg/mL. RG is therefore a promising activator in production of novel microbial metabolite.

Benzopyran derivatives from endophytic Daldinia eschscholzii JC-15 in Dendrobium chrysotoxum and their bioactivities.

Five new benzopyran derivatives (2-6) and a new natural product (1) were isolated from endophytic Daldinia eschscholzii in Dendrobium chrysotoxum and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one (1), (2R, 4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol (2), (R)-3-methoxyl-1-(2,6-dihydroxy phenyl)-butan-1-one (3), 7-O-α-d-ribosyl-5-hydroxy-2-methyl-4H-chromen-4-one (4), 7-O-α-d-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one (5), daldinium A (6). These compounds were evaluated for their antimicrobial activity, anti-acetylcholinesterase, nitric oxide inhibition, anticoagulant, photodynamic antimicrobial activities and glucose uptake of adipocytes. Some compounds showed photoactive antimicrobial activities and glucose uptake stimulating activities.

New azaphilones and tremulane sesquiterpene from endophytic Nigrospora oryzae cocultured with Irpex lacteus.

Five new metabolites belonging to two backbones of pulvilloric acid-type azaphilone and tremulane sesquiterpene were obtained and their structures were determined by spectral analysis. Based on the biogenesis analysis, tremulane sesquiterpenes were obtained from Irpex lacteus by the stimulation of mixed-culture. The antifungal selectivities of metabolites produced by fungus against their co-culture fungus and common pathogens, exhibited competitive interaction of this mix-culture. The tremulane sesquiterpene conocenol B produced by I. lacteus through the induction of Nigrospora oryzae showed selectivity of anti-fungal activity against its co-culture fungus, N. oryzae, with MICs at 16 µg/mL and 128 µg/mL against I. lacteus. The fungus can metabolize these new compounds to inhibit the growth of co-culture fungus while not inhibiting its own growth. Compound 5 was active against acetylcholinesterase (AChE) with a ratio of 35% at the concentration of 50 µM.

Phytotoxic, antibacterial, and antioxidant activities of mycotoxins and other metabolites from Trichoderma sp.

A new natural mycotoxin was isolated from the fermentation broth of Trichoderma sp. Jing-8 and the structure was determined as alternariol 1'-hydroxy-9-methyl ether (1), together with twelve known compounds. The structures were elucidated on the basis of their 1D, 2D NMR spectra and mass spectrometric data. Compounds 1, 8 and 9 indicated inhibitions against germination of the seeds of cabbage with MICs < 3 µg/mL. The compound 1 showed the antibacterial activity against Bacillus subtilis and Staphylococcus aureus with MICs at 64 µg/mL. Compound 1 and 3 showed significant DPPH radical-scavenging activities with IC50 at 12 µg/mL, respectively. The OH at C-1' in compound 1 decreased the cytotoxicity of these mycotoxins. A primary structure-activity relationship about the alternariol derivatives was discussed. Compounds 2-7 and 8 were the first time to be isolated from the Trichoderma.

Anti-rheumatic drug iguratimod (T-614) alleviates cancer-induced bone destruction via down-regulating interleukin-6 production in a nuclear factor-κB-dependent manner.

Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 µg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.