Abstract
The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA) was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and inhibited the levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α and IL-6 messenger RNA (mRNA) expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α), p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which provided useful information for its application and development.
Keywords:
anti-inflammation; mitogen-activated protein kinase; nuclear transcription factor kappa-B alpaha; scandoside.
MeSH terms
-
Animals
-
Anti-Inflammatory Agents / chemistry
-
Anti-Inflammatory Agents / isolation & purification
-
Anti-Inflammatory Agents / pharmacology*
-
Cell Survival / drug effects
-
Cyclooxygenase 2 / chemistry
-
Cyclooxygenase 2 / genetics
-
Cyclooxygenase 2 / metabolism
-
Dinoprostone / antagonists & inhibitors
-
Dinoprostone / biosynthesis
-
Hedyotis / chemistry*
-
I-kappa B Kinase / antagonists & inhibitors
-
I-kappa B Kinase / chemistry
-
I-kappa B Kinase / genetics
-
I-kappa B Kinase / metabolism
-
Interleukin-6 / genetics
-
Interleukin-6 / metabolism
-
Iridoids / chemistry
-
Iridoids / isolation & purification
-
Iridoids / pharmacology*
-
JNK Mitogen-Activated Protein Kinases / genetics
-
JNK Mitogen-Activated Protein Kinases / metabolism
-
Lipopolysaccharides / antagonists & inhibitors*
-
Lipopolysaccharides / pharmacology
-
Mice
-
Mitogen-Activated Protein Kinase 1 / genetics
-
Mitogen-Activated Protein Kinase 1 / metabolism
-
Mitogen-Activated Protein Kinase 3 / genetics
-
Mitogen-Activated Protein Kinase 3 / metabolism
-
Molecular Docking Simulation
-
NF-kappa B / antagonists & inhibitors*
-
NF-kappa B / genetics
-
NF-kappa B / metabolism
-
Nitric Oxide / antagonists & inhibitors
-
Nitric Oxide / biosynthesis
-
Nitric Oxide Synthase Type II / antagonists & inhibitors
-
Nitric Oxide Synthase Type II / chemistry
-
Nitric Oxide Synthase Type II / genetics
-
Nitric Oxide Synthase Type II / metabolism
-
Plant Extracts / chemistry
-
RAW 264.7 Cells
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / metabolism
-
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
-
p38 Mitogen-Activated Protein Kinases / genetics
-
p38 Mitogen-Activated Protein Kinases / metabolism
Substances
-
Anti-Inflammatory Agents
-
Interleukin-6
-
Iridoids
-
Lipopolysaccharides
-
NF-kappa B
-
Plant Extracts
-
Tumor Necrosis Factor-alpha
-
interleukin-6, mouse
-
Nitric Oxide
-
Nitric Oxide Synthase Type II
-
Nos2 protein, mouse
-
Ptgs2 protein, mouse
-
Cyclooxygenase 2
-
I-kappa B Kinase
-
JNK Mitogen-Activated Protein Kinases
-
Mapk1 protein, mouse
-
Mitogen-Activated Protein Kinase 1
-
Mitogen-Activated Protein Kinase 3
-
p38 Mitogen-Activated Protein Kinases
-
Dinoprostone