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Molecular and Cellular Biochemistry

, Volume 445, Issue 1–2, pp 169–178 | Cite as

Falcarindiol inhibits LPS-induced inflammation via attenuating MAPK and JAK-STAT signaling pathways in murine macrophage RAW 264.7 cells

  • Thamizhiniyan Venkatesan
  • Young-Woong Choi
  • Jennifer Lee
  • Young-Kyoon KimEmail author
Article

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.

Graphical Abstract

Keywords

Cnidium officinale Rhizome Falcarindiol RAW 264.7 cells Anti-inflammatory activity 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Thamizhiniyan Venkatesan
    • 1
  • Young-Woong Choi
    • 1
  • Jennifer Lee
    • 1
  • Young-Kyoon Kim
    • 1
    Email author
  1. 1.Department of Forest Products and Biotechnology, College of Science and TechnologyKookmin UniversitySeoulSouth Korea

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