ZFIN ID: ZDB-PUB-201007-9
Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish
Foulkes, M.J., Tolliday, F.H., Henry, K.M., Renshaw, S.A., Jones, S.
Date: 2020
Source: PLoS One   15: e0240231 (Journal)
Registered Authors: Henry, Katherine, Renshaw, Steve A.
Keywords: none
MeSH Terms:
  • Abietanes/chemical synthesis
  • Abietanes/chemistry
  • Abietanes/pharmacology*
  • Animals
  • Animals, Genetically Modified
  • Anti-Inflammatory Agents, Non-Steroidal/pharmacology*
  • Apoptosis/drug effects
  • Humans
  • Inflammation/drug therapy*
  • Molecular Structure
  • Naphthoquinones/chemistry
  • Naphthoquinones/pharmacology
  • Neutrophil Infiltration/drug effects
  • Zebrafish
PubMed: 33022012 Full text @ PLoS One
ABSTRACT
During inflammation, dysregulated neutrophil behaviour can play a major role in a range of chronic inflammatory diseases, for many of which current treatments are generally ineffective. Recently, specific naturally occurring tanshinones have shown promising anti-inflammatory effects by targeting neutrophils in vivo, yet such tanshinones, and moreover, their isomeric isotanshinone counterparts, are still a largely underexplored class of compounds, both in terms of synthesis and biological effects. To explore the anti-inflammatory effects of isotanshinones, and the tanshinones more generally, a series of substituted tanshinone and isotanshinone analogues was synthesised, alongside other structurally similar molecules. Evaluation of these using a transgenic zebrafish model of neutrophilic inflammation revealed differential anti-inflammatory profiles in vivo, with a number of compounds exhibiting promising effects. Several compounds reduce initial neutrophil recruitment and/or promote resolution of neutrophilic inflammation, of which two also result in increased apoptosis of human neutrophils. In particular, the methoxy-substituted tanshinone 39 specifically accelerates resolution of inflammation without affecting the recruitment of neutrophils to inflammatory sites, making this a particularly attractive candidate for potential pro-resolution therapeutics, as well as a possible lead for future development of functionalised tanshinones as molecular tools and/or chemical probes. The structurally related β-lapachones promote neutrophil recruitment but do not affect resolution. We also observed notable differences in toxicity profiles between compound classes. Overall, we provide new insights into the in vivo anti-inflammatory activities of several novel tanshinones, isotanshinones, and structurally related compounds.
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