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

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.

• Authors: Thamizhiniyan Venkatesan, Young-Woong Choi, Jennifer Lee, Young-Kyoon Kim
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 445 Issue 1-2 Pg. 169-178 (Aug 2018) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 29368095 (Publication Type: Journal Article)

Chemical References

• Diynes
• Fatty Alcohols
• Interleukin-1beta
• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• STAT1 Transcription Factor
• STAT3 Transcription Factor
• Stat1 protein, mouse
• Stat3 protein, mouse
• Tumor Necrosis Factor-alpha
• Flavin-Adenine Dinucleotide
• falcarindiol
• Nitric Oxide Synthase Type II
• Janus Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Araliaceae (chemistry)
• Diynes (pharmacology)
• Fatty Alcohols (pharmacology)
• Flavin-Adenine Dinucleotide (pharmacology)
• Inflammation (chemically induced)
• Interleukin-1beta (genetics)
• Interleukin-6 (genetics)
• Janus Kinases (metabolism)
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• MAP Kinase Signaling System (drug effects)
• Macrophages (drug effects, enzymology, metabolism)
• Mice
• NF-kappa B (metabolism)
• Nitric Oxide Synthase Type II (genetics)
• Proto-Oncogene Proteins c-akt (metabolism)
• RAW 264.7 Cells
• STAT1 Transcription Factor (metabolism)
• STAT3 Transcription Factor (metabolism)
• Tumor Necrosis Factor-alpha (genetics)