Grilled nux vomica alleviates myasthenia gravis by inhibiting the JAK2/STAT3 signaling pathway: a study in a mice model.
Animals
Janus Kinase 2
/ metabolism
STAT3 Transcription Factor
/ metabolism
Mice
Signal Transduction
/ drug effects
Disease Models, Animal
Myasthenia Gravis
/ drug therapy
Pyrimidines
/ pharmacology
Mice, Inbred C57BL
Drugs, Chinese Herbal
/ pharmacology
Female
Myasthenia Gravis, Autoimmune, Experimental
/ drug therapy
Tyrphostins
/ pharmacology
Receptor Protein-Tyrosine Kinases
/ metabolism
Nitriles
/ pharmacology
Pyrazoles
Grilled nux vomica
Inflammation
JAK2/STAT3 pathway
Myasthenia gravis
Neuromuscular disorder
Journal
European journal of medical research
ISSN: 2047-783X
Titre abrégé: Eur J Med Res
Pays: England
ID NLM: 9517857
Informations de publication
Date de publication:
21 Oct 2024
21 Oct 2024
Historique:
received:
20
08
2024
accepted:
08
10
2024
medline:
22
10
2024
pubmed:
22
10
2024
entrez:
21
10
2024
Statut:
epublish
Résumé
Grilled Nux Vomica (GNV) is a promising traditional Chinese medicine to treat myasthenia gravis (MG), but its effects and mechanisms need further exploration. Experimental autoimmune MG (EAMG) model was established by muscle-specific kinase (MuSK) induction on C57BL/6 J mice. Mice were treated with GNV and/or ruxolitinib (JAK2 inhibitor) or AG490 (STAT3 inhibitor) for 30 days via gavage after modeling and randomized into 7 groups: control, model, low-dose GNV, middle-dose GNV, high-dose GNV, GNV + ruxolitinib, GNV + AG490. Body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity (agrin and acetylcholine receptor [AChR] levels), inflammatory factors (IL-2 and IL-6), and the activation of the JAK2/STAT3 pathway were measured and compared between groups. GNV significantly improved body weight and muscle strength, as well as reduced clinical scores, MuSK levels, and inflammatory markers (IL-2 and IL-6) levels compared with untreated EAMG mice. GNV also protected the neuromuscular junction and increased agrin and AChR co-expression in a dose-dependent manner. In addition, GNV attenuated the levels of p-JAK2 and p-STAT3, which are aberrantly upregulated in EAMG mice. After co-treatment with ruxolitinib or AG490, the effect of GNV on body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity, levels of inflammatory factors, and JAK2/STAT3 pathway was further amplified in EAMG mice. GNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.
Sections du résumé
BACKGROUND
BACKGROUND
Grilled Nux Vomica (GNV) is a promising traditional Chinese medicine to treat myasthenia gravis (MG), but its effects and mechanisms need further exploration.
METHODS
METHODS
Experimental autoimmune MG (EAMG) model was established by muscle-specific kinase (MuSK) induction on C57BL/6 J mice. Mice were treated with GNV and/or ruxolitinib (JAK2 inhibitor) or AG490 (STAT3 inhibitor) for 30 days via gavage after modeling and randomized into 7 groups: control, model, low-dose GNV, middle-dose GNV, high-dose GNV, GNV + ruxolitinib, GNV + AG490. Body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity (agrin and acetylcholine receptor [AChR] levels), inflammatory factors (IL-2 and IL-6), and the activation of the JAK2/STAT3 pathway were measured and compared between groups.
RESULTS
RESULTS
GNV significantly improved body weight and muscle strength, as well as reduced clinical scores, MuSK levels, and inflammatory markers (IL-2 and IL-6) levels compared with untreated EAMG mice. GNV also protected the neuromuscular junction and increased agrin and AChR co-expression in a dose-dependent manner. In addition, GNV attenuated the levels of p-JAK2 and p-STAT3, which are aberrantly upregulated in EAMG mice. After co-treatment with ruxolitinib or AG490, the effect of GNV on body weight, muscle strength, clinical score, MuSK level, neuromuscular junction integrity, levels of inflammatory factors, and JAK2/STAT3 pathway was further amplified in EAMG mice.
CONCLUSIONS
CONCLUSIONS
GNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.
Identifiants
pubmed: 39434147
doi: 10.1186/s40001-024-02100-2
pii: 10.1186/s40001-024-02100-2
doi:
Substances chimiques
Janus Kinase 2
EC 2.7.10.2
STAT3 Transcription Factor
0
Jak2 protein, mouse
EC 2.7.10.2
Stat3 protein, mouse
0
Pyrimidines
0
Drugs, Chinese Herbal
0
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
0
ruxolitinib
82S8X8XX8H
Tyrphostins
0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Nitriles
0
Pyrazoles
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
507Subventions
Organisme : Natural Science Foundation of Zhejiang Province
ID : LQ20H270015
Organisme : Natural Science Foundation of Zhejiang Province
ID : GD21H270008
Informations de copyright
© 2024. The Author(s).
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