The genus Talaromyces belongs to the phylum Ascomycota of the kingdom Fungi. Studies have shown that Talaromyces species yield many kinds of secondary metabolites, including esters, terpenes, steroids, alkaloids, polyketides, and anthraquinones, some of which have biological activities such as anti-inflammatory, bacteriostatic, and antitumor activities. The chemical constituents of fungi belonging to the genus Talaromyces that have been studied by researchers over the past several years, as well as their biological activities, are reviewed here to provide a reference for the development of high-value natural products and innovative uses of these resources.

No abstract

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.

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.

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.

Excessive inflammation causes chronic diseases and tissue damage. Although there has been drug treatment, its side effects are relatively large. Searching for effective anti-inflammatory drugs from natural products has become the focus of attention. First isolated from Trichoderma longibraciatum, trichodimerol is a natural product with TNF inhibition. In this study, lipopolysaccharide (LPS)-induced RAW264.7 macrophages were used as a model to investigate the anti-inflammatory activity of trichodimerol. The results of nitric oxide (NO) detection, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) showed that trichodimerol could reduce the production of NO, ROS, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Western blotting results showed that trichodimerol could inhibit the production of inflammatory mediators such as cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and the protein expression of nuclear transcription factor-kappaB (NF-κB), p-IKK, p-IκB, Toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteinyl aspartate specific proteinase (Caspase)-1, and ASC, which indicated that trichodimerol may inhibit inflammation through the NF-κB and NLRP3 pathways. At the same time, molecular docking showed that trichodimerol can directly combine with the TLR4-MD2 complex. Hence, trichodimerol inhibits inflammation by obstructing the interaction between LPS and the TLR4-MD2 heterodimer and suppressing the downstream NF-κB and NLRP3 pathways.

No abstract