PUBLICATION
In Vitro and In Vivo Anti-Inflammatory Effects of Polyphyllin VII through Downregulating MAPK and NF-κB Pathways
- Authors
- Zhang, C., Li, C., Jia, X., Wang, K., Tu, Y., Wang, R., Liu, K., Lu, T., He, C.
- ID
- ZDB-PUB-190306-1
- Date
- 2019
- Source
- Molecules 24(5): (Journal)
- Registered Authors
- Keywords
- anti-inflammation, macrophage, mice, polyphyllin VII, zebrafish
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/chemistry
- Anti-Inflammatory Agents/pharmacology*
- Cyclooxygenase 2/genetics
- Dinoprostone/genetics
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Gene Expression Regulation/drug effects
- Humans
- Inflammation/chemically induced
- Inflammation/drug therapy*
- Inflammation/pathology
- Interleukin-1beta/genetics
- Interleukin-6/genetics
- Lipopolysaccharides/toxicity
- MAP Kinase Kinase 1/genetics
- Mice
- NF-kappa B/genetics
- Nitric Oxide/genetics*
- Nitric Oxide Synthase Type II/genetics
- RAW 264.7 Cells/drug effects
- Saponins/chemistry
- Saponins/pharmacology*
- Signal Transduction/drug effects
- Tumor Necrosis Factor-alpha/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 30832224 Full text @ Molecules
Citation
Zhang, C., Li, C., Jia, X., Wang, K., Tu, Y., Wang, R., Liu, K., Lu, T., He, C. (2019) In Vitro and In Vivo Anti-Inflammatory Effects of Polyphyllin VII through Downregulating MAPK and NF-κB Pathways. Molecules. 24(5).
Abstract
Background: Polyphyllin VII (PP7), a steroidal saponin from Paris polyphylla, has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models. Methods: The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE₂) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models. Results: PP7 reduced the production of NO and PGE₂ and the protein and mRNA expressions of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and enzymes (inducible NO synthase [iNOS], cyclooxygenase-2 [COX-2], and Matrix metalloproteinase-9 [MMP-9]) in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO₄-induced inflammation and toxicity in zebrafish embryos. Conclusion: This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping