Esculentoside B inhibits inflammatory response through JNK and downstream NF-κB signaling pathway in LPS-triggered murine macrophage RAW 264.7 cells.

Abstract

Natural compound esculentoside B (EsB), (2S,4aR,6aR,6aS,6bR,8aR,9R,10R,11S,12aR,14bS)-11-hydroxy-9-(hydroxymethyl)-2 methoxycarbonyl-2,6a,6b,9,12a-pentamethyl-10-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxy-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid with molecular weight of 664.833, isolated from roots of Phytolacca acinosa Roxb has been widely used as a constituent of traditional Chinese medicine (TCM). However, the anti-inflammatory capacity of EsB has not been reported yet. Therefore, the objective of this study was to investigate anti-inflammatory activities of EsB in LPS-treated macrophage RAW 264.7 cells. EsB could inhibit nitric oxide (NO) production. EsB also suppressed gene and protein expression levels of inducible isoform of NO synthase (NOS) and cyclooxygenase-2 in a dose-dependent manner. In addition, EsB decreased gene expression and protein secretion levels of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6. EsB remarkably suppressed nuclear translocation of nuclear factor kappa-B (NF-κB) from cytosolic space. Phosphorylation of IκB was also inhibited by EsB. Moreover, EsB specifically down-regulated phospho-c-Jun N-terminal kinase (p-JNK), but not p-p38 or phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2). Taken together, these results suggest that EsB has inhibitory effect on inflammatory response by inactivating NF-κB and p-JNK. It could be used as a new modulatory drug for effective treatment of inflammation-related diseases.

• Authors: Fukushi Abekura, Junyoung Park, Choong-Hwan Kwak, Sun-Hyung Ha, Seung-Hak Cho, Young-Chae Chang, Ki-Tae Ha, Hyeun-Wook Chang, Young-Choon Lee, Tae-Wook Chung, Cheorl-Ho Kim
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 68 Pg. 156-163 (Mar 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30639961 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Lipopolysaccharides
• NF-kappa B
• Saponins
• Terpenes
• Nitric Oxide
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, pharmacology)
• Cell Survival (drug effects)
• Cytokines (genetics, metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Lipopolysaccharides
• Macrophages (drug effects, metabolism)
• Mice
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• RAW 264.7 Cells
• Saponins (chemistry, pharmacology)
• Signal Transduction (drug effects)
• Terpenes (chemistry, pharmacology)