C16 peptide and angiopoietin-1 alleviate the side effects of glucocorticoids in a rat multiple sclerosis model

Background: Natural glucocorticoids (GCs) have been widely used to treat acute multiple sclerosis (MS) attacks. However, they also cause significant side effects related to immunosuppression. Our previous study found that C16 peptide combined with angiopoietin-1 (ANG-1) inhibited inflammatory cell infiltration and protected blood vessels in animal models of inflammatory neurodegenerative diseases.

Methods: An acute experimental autoimmune encephalomyelitis model was established in Lewis rats to explore the effects of these drugs on MS. One hundred rats were equally and randomly assigned into five groups: normal control, vehicle, low-dose methylprednisolone (MP), high-dose MP, and C16 + ANG-1 (C+A). Histological examinations, behavioral tests, and high-throughput 16S rRNA gene Sequencing were conducted to determine inflammation levels in the central nervous system, neuronal survival, functional recovery and gut microbiota.

Results: The results illustrated that C+A exerted a neuroprotective effect in MS rats, with fewer side effects observed in the C+A group than in the high-dose MP group. The abundance of Campylobacter was increased in vehicle-treated rats, indicating an imbalance of the gut microbiota after MS. The abundance of probiotic Lactobacillus plantarum was increased in the C+A group. Low-dose MP failed to reverse the gut microbiota imbalance, whereas both the C+A and high-dose MP groups exhibited gut microbiota profiles more similar to those of the normal controls, with C+A displaying superior efficacy.

Conclusions: C16 plus ANG-1 might serve as a complement to GCs for the treatment of MS. Changes in the abundance of Campylobacter and L. plantarum suggest their essential roles in the pathogenesis of MS.

Angiopoietin-1; C16 peptide; Glucocorticoids; Inflammation; Multiple sclerosis; Side effects.