Chaetoglobosin Fex from the Marine-Derived Endophytic Fungus Inhibits Induction of Inflammatory Mediators via Toll-Like Receptor 4 Signaling in Macrophages

Dou, Huan; Song, Yuxian; Liu, Xianqin; Gong, Wei; Li, Erguang; Tan, Renxiang; Hou, Yayi

doi:10.1248/bpb.34.1864

Cited by 43 publications

(31 citation statements)

References 45 publications

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“…The current knowledge on the structure and function of the TLR4 has opened the possibility to develop new drug targets to fight sepsis associated with this signaling molecule. In an effort to search for novel TLR4 signaling regulators from endophytic metabolites in our lab, we tested more than 300 natural products for their ability to reduce inflammatory mediator production from LPS-stimulated RAW 264.7 macrophages (30). Based on FC bioactivity backbone, FC-99 ( Figure 1A) shows a novel structure, and this is the first study to exhibit protective effects in two murine models of sepsis.…”

Section: Discussionmentioning

confidence: 99%

A Novel Benzenediamine Derivate Rescued Mice from Experimental Sepsis by Attenuating Proinflammatory Mediators via IRAK4

Dou

Song

Liu

et al. 2014

Am J Respir Cell Mol Biol

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We designed and synthesized a novel benzenediamine derivate, FC-99, that was tested for its ability to protect mice from experimental sepsis. Moreover, we sought to determine whether FC-99 could control a bacterial infection and to clarify the mechanism by which FC-99 inhibited LPS-activated macrophages. The effects of FC-99 on inflammation were evaluated in two experimental sepsis models and in cultured macrophages. Microarrays and docking and molecular dynamics simulations were used to determine the target of FC-99. Surface plasmon resonance and molecular detection were performed to confirm the direct interaction of FC-99 with its target. FC-99 protected mice from experimental sepsis. The mice that received FC-99 exhibited a diminished inflammatory response, had a lower local bacterial burden, and experienced a significantly improved survival rate. Genome-wide transcriptional profiling of FC-99-treated macrophages identified IRAK4 as a drug-regulated gene involved in LPS/TLR4 signaling. A computer search and calculations indicated that IRAK4 directly interacted with FC-99. Surface plasmon resonance, IRAK4-regulated signaling pathway analysis, and gene expression profiling of proinflammatory mediators confirmed the direct interaction between FC-99 and IRAK4. FC-99 is a potential therapeutic molecule for sepsis that alleviated experimental sepsis by directly inhibiting IRAK4 activation, which represents a novel target for sepsis therapy.

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Section: Discussionmentioning

confidence: 99%

A Novel Benzenediamine Derivate Rescued Mice from Experimental Sepsis by Attenuating Proinflammatory Mediators via IRAK4

Dou

Song

Liu

et al. 2014

Am J Respir Cell Mol Biol

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“…Furthermore, Cha Fex didn't affect LPS binding to the RAW264.7 cells and human monocytes, while Cha Fex has able to inhibit the increase of membrane-associated CD14 (mCD14) expression both on RAW cells and human monocytes induced by LPS to a certain degree. These results suggest that the anti-inflammatory property of Cha Fex may be attributed to NF-kB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations [65].…”

Section: Anti-inflammatory Metabolitesmentioning

confidence: 77%

Natural Products with Anticancer Activity from Marine Fungi

Karuppiah

Zhang

2014

Handbook of Anticancer Drugs From Marine Origin

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Cancer is one of the major diseases, which require the improved drugs with fewer side effects. Until now, several marine natural products have been accessed for the anticancer property and few of them are in clinical trials too. Marine fungi are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The natural products isolated from the marine fungi are possibly inhibiting the processes such as inflammation, cell differentiation and survival, and metastasis of various signal transduction pathways and their by reducing the risk of cancer. In this chapter, we have discussed about the anticancer, anti-inflammatory and cytotoxic activities of marine derived fungi.

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“…Based on such a targeted approach, NFjB inhibition is a plausible mechanism for the treatment or prevention of cancer (Schupp et al 2009;Luqman & Pezzuto 2010). Some fungal metabolites reported for potential to inhibit NFjB include trichodion, tricyclic acid, panepoxydone, hispidin derivatives, chaetoglobosin and mycoepoxydiene (Erkel 2000;Wijeratne et al 2003;Erkel et al 2007;Dou et al 2011;Wu et al 2011;Wang et al 2012). In our study, six of the isolates presented more than 60% NFjB inhibition, suggesting their potential to produce cancer chemopreventive compounds.…”

Section: Discussionmentioning

confidence: 99%

Endophytic fungi associated withTaxus fuana(West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

Fatima

Kondratyuk

Park

et al. 2016

Pharmaceutical Biology

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Context: Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery. Objective: Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity. Materials and methods: Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-ainduced NFjB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells. Results: Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFjB activity (IC 50 values ranging between 0.18 and 17 lg/mL) and five inhibited iNOS (IC 50 values ranging between 0.32 and 12.9 lg/mL). In the aromatase assay, only two isolates mediated inhibition (IC 50 values 12.2 and 10.5 lg/ mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5 lg/mL), and five extracts inhibited the growth of MCF-7 cells (IC 50 values ranging from 0.56 to 17.5 lg/mL). Six active cultures were derived from woody parts of the plant material. Conclusion: The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents. ARTICLE HISTORY

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Chaetoglobosin Fex from the Marine-Derived Endophytic Fungus Inhibits Induction of Inflammatory Mediators via Toll-Like Receptor 4 Signaling in Macrophages

Cited by 43 publications

References 45 publications

A Novel Benzenediamine Derivate Rescued Mice from Experimental Sepsis by Attenuating Proinflammatory Mediators via IRAK4

A Novel Benzenediamine Derivate Rescued Mice from Experimental Sepsis by Attenuating Proinflammatory Mediators via IRAK4

Natural Products with Anticancer Activity from Marine Fungi

Endophytic fungi associated withTaxus fuana(West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

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