Abstract
Falcarindiol (FAD) is a natural polyacetylene compound found rich in many plants of the Umbelliferae family. Previously, we isolated FAD from the rhizome of Cnidium officinale Makino, which belongs to the Umbelliferae family and found it to have a significant inhibitory effect on lipopolysaccharide (LPS)-induced production of nitric oxide, a pro-inflammatory molecule in murine macrophage RAW 264.7 cells. In this study, we investigated its effect on the expression of other major pro-inflammatory molecules as well as the mechanism underlying these effects. Pre-treatment of RAW 264.7 cells with FAD suppressed LPS-stimulated mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) and thereby reduced the respective protein levels. Mechanistic studies demonstrated that FAD attenuated the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling molecules. Moreover, we found that FAD did not influence LPS-induced activation of p38 and NFκB signaling pathways. Collectively, this study provides evidence that FAD inhibits the production of major pro-inflammatory molecules in LPS-challenged murine macrophages via suppression of JNK, ERK, and STAT signaling pathways.
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Abbreviations
- BCA:
-
Bicinchoninic acid
- BSA:
-
Bovine serum albumin
- cDNA:
-
Complementary deoxyribonucleic acid
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- DMSO:
-
Dimethyl sulfoxide
- E. coli :
-
Escherichia coli
- ERK:
-
Extracellular signal–regulated kinase
- FAD:
-
Falcarindiol
- FBS:
-
Fetal bovine serum
- IL-1β:
-
Interleukin-1β
- HBSS:
-
Hank’s balanced salt solution
- HEPES:
-
4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, N-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)
- HRP:
-
Horseradish peroxidase
- IκB:
-
Inhibitory kappa B protein
- IL-6:
-
Interleukin-6
- iNOS:
-
Inducible nitric oxide synthase
- JAK-STAT:
-
Janus kinase-signal transducers and activators of transcription
- JNK:
-
c-Jun N-terminal kinase
- LPS:
-
Lipopolysaccharide
- MAPKs:
-
Mitogen-activated protein kinases
- mRNA:
-
Messenger RNA
- MTT:
-
(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)
- NaCl:
-
Sodium chloride
- NFκB:
-
Nuclear transcription factor kappa B
- NO:
-
Nitric oxide
- P38:
-
P38 Mitogen-activated protein kinase
- PBS:
-
Phosphate-buffered saline
- qRT-PCR:
-
Quantitative real-time polymerase chain reaction
- RIPA:
-
Radioimmunoprecipitation assay
- RNA:
-
Ribonucleic acid
- SDS:
-
Sodium dodecyl sulfate
- STAT1:
-
Signal transducers and activators of transcription factor 1
- STAT3:
-
Signal transducers and activators of transcription factor 3
- TLR4:
-
Toll-like receptor 4
- TNF-α:
-
Tumor necrosis factor α
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Funding
The funding was provided by Forest Science & Technology Projects, Forest Service, Republic of Korea (Grant No. S211316L010110), Kookmin University (KR) research grant (Grant No. 2016)
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Venkatesan, T., Choi, YW., Lee, J. et al. Falcarindiol inhibits LPS-induced inflammation via attenuating MAPK and JAK-STAT signaling pathways in murine macrophage RAW 264.7 cells. Mol Cell Biochem 445, 169–178 (2018). https://doi.org/10.1007/s11010-017-3262-z
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DOI: https://doi.org/10.1007/s11010-017-3262-z