Tripterygium glycoside tablets and triptolide alleviate experimental autoimmune encephalomyelitis mice involving the PACAP/cAMP signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE

Tripterygiumwilfordii, a traditional Chinese herbal medicine, has been used for treating autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. Tripterygium glycoside tablets (TGT), derived from this herb, is widely used in clinical practice in China. However, the therapeutic effects of TGT on Multiple sclerosis (MS), particularly through its active component triptolide (TP), remain insufficiently understood.

AIM OF THE STUDY

This study aimed to investigate the therapeutic effects of TGT and TP on experimental autoimmune encephalomyelitis (EAE) and elucidate the underlying molecular mechanisms.

MATERIALS AND METHODS

TGT and TWPT were chemically characterized using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The therapeutic effect of TGT, TWPT, and TP was evaluated in the EAE model. Proteomics analysis and Western blot analysis were validated the signaling pathways.

RESULTS

TGT and TP significantly alleviated EAE symptoms in mice, including reduced weight loss and neurological deficits, whereas TWPT (TGT without triptolide) shows no significant therapeutic effect. Histological analysis revealed that TGT and TP reduced demyelination and inflammatory cell infiltration in the spinal cord. TGT and TP decreased systemic inflammatory cytokines (IL-17A, IFN-γ, TNF-α, and IL-6) and the mRNA expression of the transcription factors T-bet and ROR-γt in the spinal cord. Proteomic analysis indicated that TP significantly upregulated the expression of PACAP and activated the cAMP signaling pathway. Furthermore, TGT and TP modulate PKA, PI3K-AKT, NF-κB, and apoptosis-related signaling pathways, contributing to the reducing inflammation, apoptosis and demyelination in EAE mice.

CONCLUSION

TGT and TP exert anti-inflammatory and demyelination-improving effects to alleviate both clinical and pathological manifestations of EAE in mice via the PACAP/cAMP signaling axis, suggesting TGT as promising therapeutic strategies for MS.