Background
Grilled Nux Vomica (GNV) is a promising traditional Chinese medicine to treat myasthenia gravis (MG), but its effects and mechanisms need further exploration.
Conclusions
GNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.
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
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: GNV improves MG by inhibiting the JAK2/STAT3 pathway, which might be an effective therapeutic strategy for MG.