JAX2, an ethanol extract of Hyssopus cuspidatus Boriss, can prevent bronchial asthma by inhibiting MAPK/NF-κB inflammatory signaling.
Animals
Anti-Asthmatic Agents
/ pharmacology
Asthma
/ metabolism
Disease Models, Animal
Ethanol
/ chemistry
Female
Hyssopus Plant
/ chemistry
Lipopolysaccharides
/ pharmacology
MAP Kinase Signaling System
/ drug effects
Male
Mice
NF-kappa B
/ metabolism
Nitric Oxide
/ metabolism
Phosphorylation
/ drug effects
Plant Extracts
/ chemistry
RAW 264.7 Cells
Rats, Sprague-Dawley
Signal Transduction
/ drug effects
Anti-inflammatory
Bronchial asthma
Hyssopus cuspidatus Boriss
MAPK
NF-κB
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
07
08
2018
revised:
18
12
2018
accepted:
29
12
2018
pubmed:
27
2
2019
medline:
25
6
2019
entrez:
27
2
2019
Statut:
ppublish
Résumé
Hyssopus cuspidatus Boriss has been used to treat bronchial asthma for many years in Uighur medicine. JAX2, an ethanol extract from this plant, has effectiveness against bronchial asthma. However, the molecular basis for the anti-inflammatory effects of JAX2 remains unclear. This study aimed to evaluate the mechanism of JAX2 against bronchial asthma. We established an asthma model in rats using ovalbumin (OVA), and an inflammatory model in RAW264.7 cells using lipopolysaccharide (LPS) stimulation. To evaluate the anti-inflammatory effects of JAX2, the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-17, eotaxin and immunoglobulin (Ig)E were measured by enzyme-linked immunosorbent assay (ELISA). Cell viability was investigated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay. Further, nitric oxide (NO) and reactive oxygen species (ROS) were determined using Griess reagent and 2,7-dichlorofluorescein diacetate. The phosphorylation of p-extracellular signal-regulated kinase (ERK), p-Jun-NH2-terminal kinase (JNK), p38 kinases (p38) and p-inhibitor of nuclear factor kappa-B kinase (IKK), and nuclear translocation of p-p65 kinases (p-p65) were determined by immunofluorescence to uncover the effects of JAX2 on the Mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. After JAX2 administration to rats, Interferon (IFN)-γ concentrations in BALF increased significantly. Further, the concentrations of TNF-α, IL-4, IL-6, IL-17 and eotaxin in BALF, and IgE in serum decreased. JAX2 decreased TNF-α, IL-6 and NO in cell supernatant, and reduced ROS intracellularly. Concurrently, IFN-γ concentrations increased in cell supernatant significantly. In LPS-induced RAW264.7 cells, JAX2 inhibited phosphorylation of p-ERK, p-JNK and p-38 MAPK. The subsequent phosphorylation of p-IKK and nuclear translocation of the p-p65 subunit of NF-κB were also suppressed. Based on these findings, we believe that JAX2 has both preventive and treatment effects in bronchial asthma. Furthermore, in the RAW264.7 cell inflammatory model, JAX2 also inhibited NF-κB and MAPK signaling pathways.
Sections du résumé
BACKGROUND
BACKGROUND
Hyssopus cuspidatus Boriss has been used to treat bronchial asthma for many years in Uighur medicine. JAX2, an ethanol extract from this plant, has effectiveness against bronchial asthma. However, the molecular basis for the anti-inflammatory effects of JAX2 remains unclear.
PURPOSE
OBJECTIVE
This study aimed to evaluate the mechanism of JAX2 against bronchial asthma.
METHODS
METHODS
We established an asthma model in rats using ovalbumin (OVA), and an inflammatory model in RAW264.7 cells using lipopolysaccharide (LPS) stimulation. To evaluate the anti-inflammatory effects of JAX2, the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-17, eotaxin and immunoglobulin (Ig)E were measured by enzyme-linked immunosorbent assay (ELISA). Cell viability was investigated by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)2H-tetrazolium, inner salt (MTS) assay. Further, nitric oxide (NO) and reactive oxygen species (ROS) were determined using Griess reagent and 2,7-dichlorofluorescein diacetate. The phosphorylation of p-extracellular signal-regulated kinase (ERK), p-Jun-NH2-terminal kinase (JNK), p38 kinases (p38) and p-inhibitor of nuclear factor kappa-B kinase (IKK), and nuclear translocation of p-p65 kinases (p-p65) were determined by immunofluorescence to uncover the effects of JAX2 on the Mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways.
RESULTS
RESULTS
After JAX2 administration to rats, Interferon (IFN)-γ concentrations in BALF increased significantly. Further, the concentrations of TNF-α, IL-4, IL-6, IL-17 and eotaxin in BALF, and IgE in serum decreased. JAX2 decreased TNF-α, IL-6 and NO in cell supernatant, and reduced ROS intracellularly. Concurrently, IFN-γ concentrations increased in cell supernatant significantly. In LPS-induced RAW264.7 cells, JAX2 inhibited phosphorylation of p-ERK, p-JNK and p-38 MAPK. The subsequent phosphorylation of p-IKK and nuclear translocation of the p-p65 subunit of NF-κB were also suppressed.
CONCLUSION
CONCLUSIONS
Based on these findings, we believe that JAX2 has both preventive and treatment effects in bronchial asthma. Furthermore, in the RAW264.7 cell inflammatory model, JAX2 also inhibited NF-κB and MAPK signaling pathways.
Identifiants
pubmed: 30807985
pii: S0944-7113(18)30635-4
doi: 10.1016/j.phymed.2018.12.043
pii:
doi:
Substances chimiques
Anti-Asthmatic Agents
0
Lipopolysaccharides
0
NF-kappa B
0
Plant Extracts
0
Nitric Oxide
31C4KY9ESH
Ethanol
3K9958V90M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
305-314Informations de copyright
Copyright © 2019 Elsevier GmbH. All rights reserved.