PUBLICATION
Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish
- Authors
- Foulkes, M.J., Tolliday, F.H., Henry, K.M., Renshaw, S.A., Jones, S.
- ID
- ZDB-PUB-201007-9
- 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
Citation
Foulkes, M.J., Tolliday, F.H., Henry, K.M., Renshaw, S.A., Jones, S. (2020) Evaluation of the anti-inflammatory effects of synthesised tanshinone I and isotanshinone I analogues in zebrafish. PLoS One. 15:e0240231.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping