Aureonitol Analogues and Orsellinic Acid Esters Isolated from <i>Chaetomium elatum</i> and Their Antineuroinflammatory Activity

Ju, Feng; Kuang, Qi-Xuan; Li, Qingzhou; Huang, Lijun; Guo, Wenxiu; Gong, Lei-Qiang; Dai, Yifei; Wang, Lun; Gu, Yu‐Cheng; Wang, Dong; Deng, Yun; Guo, Da‐Le

doi:10.1021/acs.jnatprod.1c00783

Cited by 23 publications

(16 citation statements)

References 27 publications

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“…RAW264.7 macrophages were plated into 6-well plates overnight, pretreated with 2 ml medium containing DMSO (0.1%), dexamethasone (30 μM) or 1 at concentrations of 7.5, 15, and 30 μM for 1 h and incubated with LPS (1 μg/ml). The details of protein sample extraction and experimental procedures are described in our previous work ( Ju et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

Kuang

Lei²,

Li³

et al. 2022

Front. Pharmacol.

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Background: Excessive inflammation results in severe tissue damage as well as serious acute or chronic disorders, and extensive research has focused on finding new anti-inflammatory hit compounds with safety and efficacy profiles from natural products. As promising therapeutic entities for the treatment of inflammation-related diseases, fusaproliferin and its analogs have attracted great interest. However, the underlying anti-inflammatory mechanism is still poorly understood and deserves to be further investigated.Methods: For the estimation of the anti-inflammatory activity of fusaproliferin (1) and its analogs (2-4)in vitro and in vivo, lipopolysaccharide (LPS)-induced RAW264.7 macrophages and zebrafish embryos were employed. Then, transcriptome analysis was applied to guide subsequent western blot analysis of critical proteins in related signaling pathways. Surface plasmon resonance assays (SPR) combined with molecular docking analyses were finally applied to evaluate the affinity interactions between 1-4 and TLR4 and provide a possible interpretation of the downregulation of related signaling pathways.Results: 1-4 significantly attenuated the production of inflammatory messengers, including nitric oxide (NO), reactive oxygen species (ROS), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), as well as nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in LPS-induced RAW264.7 macrophages. Transcriptome analyses based on RNA-seq indicated the ability of compound 1 to reverse LPS stimulation and the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPKs) signaling pathways contribute to the anti-inflammatory process. Experimental verification at the protein level revealed that 1 can inhibit the activation of inhibitor of NF-κB kinase (IKK), degradation of inhibitor of NF-κB (IκB), and phosphorylation of NF-κB and reduce nuclear translocation of NF-κB. 1 also decreased the phosphorylation of MAPKs, including p38, extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK). SPR assays and molecular docking results indicated that 1-4 exhibited affinity for the TLR4 protein with KD values of 23.5–29.3 μM.Conclusion: Fusaproliferin and its analogs can be hit compounds for the treatment of inflammation-associated diseases.

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Section: Methodsmentioning

confidence: 99%

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

Kuang

Lei²,

Li³

et al. 2022

Front. Pharmacol.

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“…Cytotoxic activities of 1 – 19 were evaluated against the human breast cancer MBA-MD-231 cell line, the human colon cancer SW620 cell line, and RAW264.7 macrophages by measuring the reduction of metabolically active cells following standard procedures of MTT …”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Microglia are resident CNS cells that comprise 10% of the CNS population. In addition, microglia execute immune surveillance and perform macrophage-like activities, including the production of proinflammatory factors, such as interleukin (IL)-1β, interleukin-6 (IL-6) and tumor necrosis factor (TNF)-α, chemokines, small molecule messengers, such as nitric oxide, and reactive oxygen species (ROS) [ 1 , 3 , 4 ] . Uncontrolled and overactivated microglia can lead to pathological changes in the CNS and further lead to neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease [ 5 ‒ 8 ] .…”

Section: Introductionmentioning

confidence: 99%

N-acetyldopamine dimer inhibits neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 pathways

Huang¹,

Gong²,

Huo³

et al. 2022

ABBS

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Neuroinflammation mediated by microglia is an important pathophysiological mechanism in neurodegenerative diseases. However, there is a lack of effective drugs to treat neuroinflammation. N-acetyldopamine dimer (NADD) is a natural compound from the traditional Chinese medicine Isaria cicada . In our previous study, we found that NADD can attenuate DSS-induced ulcerative colitis by suppressing the NF-κB and MAPK pathways. Does NADD inhibit neuroinflammation, and what is the target of NADD? To answer this question, lipopolysaccharide (LPS)-stimulated BV-2 microglia was used as a cell model to investigate the effect of NADD on neuroinflammation. Nitric oxide (NO) detection, reactive oxygen species (ROS) detection and enzyme-linked immunosorbent assay (ELISA) results show that NADD attenuates inflammatory signals and proinflammatory cytokines in LPS-stimulated BV-2 microglia, including NO, ROS, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin-6 (IL-6). Western blot analysis show that NADD inhibits the protein levels of Toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), ASC and cysteinyl aspartate specific proteinase (Caspase)-1, indicating that NADD may inhibit neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 signaling pathways. In addition, surface plasmon resonance assays and molecular docking demonstrate that NADD binds with TLR4 directly. Our study reveals a new role of NADD in inhibiting the TLR4/NF-κB and NLRP3/Caspase-1 pathways, and shows that TLR4-MD2 is the direct target of NADD, which may provide a potential therapeutic candidate for the treatment of neuroinflammation.

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Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity

Cited by 23 publications

References 27 publications

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

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

N-acetyldopamine dimer inhibits neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 pathways

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Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity

Cited by 23 publications

References 27 publications

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

Investigation of the Anti-Inflammatory Activity of Fusaproliferin Analogues Guided by Transcriptome Analysis

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

N-acetyldopamine dimer inhibits neuroinflammation through the TLR4/NF-&kappa;B and NLRP3/Caspase-1 pathways

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N-acetyldopamine dimer inhibits neuroinflammation through the TLR4/NF-κB and NLRP3/Caspase-1 pathways