Hydroanthraquinones from Nigrospora sphaerica and Their Anti-inflammatory Activity Uncovered by Transcriptome Analysis

Abstract

Transcriptome analysis is shown to be an effective strategy to understand the potential function of natural products. Here, it is reported that 11 previously undescribed hydroanthraquinones [nigroquinones A−K (1−11)], along with eight known congeners, were isolated from Nigrospora sphaerica. Their structures were elucidated by interpreting spectroscopic and spectrometric data including high-resolution mass spectra and nuclear magnetic resonance. The absolute configurations of 1−11 were confirmed by electronic circular dichroism calculations. Transcriptome analysis revealed that 3 (isolated in the largest amount) might be antiinflammatory. Assays based on LPS-induced RAW264.7 macrophages and zebrafish embryos confirmed that some of the isolated hydroanthraquinones attenuated the secretion of pro-inflammatory mediators in vitro and in vivo. Further Western blotting and immunofluorescence experiments indicated that 4 (which showed the most obvious nitric oxide inhibition) could suppress the expression of nuclear factor-kappa-B (NF-κB), phosphorylation of the inhibitor of NF-κB kinase and inhibit the transportation of NF-κB to the nucleus. Hence, the suppression of the NF-κB signaling pathway may be responsible for the anti-inflammatory effect. These results show that bioactivity evaluation on the basis of transcriptome analysis may be effective in the functional exploration of natural products.

Alkannin reverses lipopolysaccharides-induced inflammatory responses by suppressing mitogen-activated protein kinase and nuclear factor kappa-B signalling

“…Further, 20 µL MTT (5 mg/mL, 20 µL/well) was added to each well and incubated for 4 h. Subsequently, the supernatant of each well was removed, the cells were resolved with DMSO (150 µL per well), and absorbance was measured at 490 nm using the ELX800-UV microplate reader (USA). To detect the cytotoxicity of ALK, these cells were pre-treated with 1, 3, 5, 10, and 20 μM ALK (without LPS) or phosphate buffered solution (PBS, as control) for 24 h, and the viability of these cells was determined using the MTT assay, as described previously [ 30 ].…”

Trichodimerol inhibits inflammation through suppression of the nuclear transcription factor-kappaB/NOD-like receptor thermal protein domain associated protein 3 signaling pathway

“…Due to the side effects of marketed drugs, the search for new efficacious and safe anti-inflammatory natural products with novel structures is still a focus of extensive research ( Zhong and Shi, 2019 ). Fungi are highly rewarding resources of auspicious hit compounds for inflammation-related diseases, and many anti-inflammatory natural products with novel, complex, and compact structures have been isolated from fungi ( Cao et al, 2021 ; Ju et al, 2021 ; Huang et al, 2022 ; Kuang et al, 2022a , b ). Trichodimerol is a typical natural product isolated from Trichoderma longibraciatum .…”

Caryophyllene Sesquiterpenes from a Chaetomium globosum Endophyte of the Canadian Medicinal Plant Empetrum nigrum

“…Endophytic fungi, particularly those isolated from medicinal plants, continue to be a promising source of natural products. − Fungi of the genus Chaetomium are most commonly isolated from plants − but have also been isolated from soil, terrestrial invertebrates, , and the marine environment − and represent a source of diverse, new, and bioactive natural products. ,,,,− Chaetomium globosum , in particular, displays a high capacity to produce alkaloids such as the chaetoglobosins and a variety of polyketides, many of which display antibacterial, ,, antifungal, ,, antiviral, immunosuppressive, and cytotoxic activities. − , During our investigation of endophytic fungi from North American medicinal plants, the ethyl acetate extract of a C. globosum isolate (TC2-041) was found to possess a unique metabolic profile among our extract library . Fractionation of the ethyl acetate extract of a two-week bench-scale fermentation of TC2-041 by liquid–liquid partition, reversed-phase flash chromatography, and HPLC led to the isolation of two new natural products, punctaporonin T ( 1 ) and punctaporonin U ( 2 ), along with the known punctaporonins A–C ( 3 – 5 ) .…”