PUBLICATION
A non-polar fraction of Saponaria officinalis L. acted as a TLR4/MD2 complex antagonist and inhibited TLR4/MyD88 signaling in vitro and in vivo
- Authors
- Yu, G.R., Lim, D.W., Karunarathne, W.A.H.M., Kim, G.Y., Kim, H., Kim, J.E., Park, W.H.
- ID
- ZDB-PUB-220614-14
- Date
- 2022
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36: e22387 (Journal)
- Registered Authors
- Keywords
- M1 polarization, Saponaria officinalis L, TLR4/MD2 complex, TLR4/MyD88 complex, immunomodulation, molecular docking simulation, saponarin, zebrafish
- MeSH Terms
-
- Adaptor Proteins, Signal Transducing/metabolism
- Animals
- Lipopolysaccharides/pharmacology
- Myeloid Differentiation Factor 88/metabolism
- NF-kappa B/metabolism
- Saponaria*/metabolism
- Signal Transduction/physiology
- Toll-Like Receptor 4*/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism
- PubMed
- 35696068 Full text @ FASEB J.
Citation
Yu, G.R., Lim, D.W., Karunarathne, W.A.H.M., Kim, G.Y., Kim, H., Kim, J.E., Park, W.H. (2022) A non-polar fraction of Saponaria officinalis L. acted as a TLR4/MD2 complex antagonist and inhibited TLR4/MyD88 signaling in vitro and in vivo. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 36:e22387.
Abstract
Targeting Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD2) signaling is regarded as a potential strategy for treating inflammatory diseases. Saponaria officinalis L. is rich in saponin, which include quillaic acid, gypsogenin, saponarin, and hederagenin. We evaluated the pharmacological activity of a Saponaria officinalis extract in THP-1 derived macrophages and RAW264.7 macrophages. TLR4/MyD88 complex formation and downstream signals were investigated by co-immunoprecipitation (Co-IP). In silico docking simulation was conducted to predict binding scores and perform 3D modeling of saponarin-TLR4/MD2 complex. A hexane fraction of Saponaria officinalis (SH) and fr.1 (a sub-fraction 1 of SH) inhibited mitogen-activated protein kinase (MAPK) signaling, nuclear factor kappa b (NF-κB) activity, cytokine production, and the expressions of marker genes specific for M1 polarization. The inhibitory effects of fr.1 and saponarin on TLR4/MyD88 complex formation were observed by western blotting TLR4 co-immunoprecipitated proteins. Saponarin and fr.1 markedly attenuated LPS-induced inflammatory cytokines, thus reducing mortality and morphological abnormality in zebrafish larvae. Finally, docking simulation revealed that saponarin can directly interact with TLR4/MD2 complex to inhibit downstream signalings. Our findings suggest that saponarin reduces downstream inflammatory response by disrupting TLR4/MD2 complex and blocking MyD88-dependent inflammatory signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping