Fucosylated Chondroitin Sulfate against Parkinson's Disease through Inhibiting Inflammation Induced by Gut Dysbiosis

J Agric Food Chem. 2022 Oct 26;70(42):13676-13691. doi: 10.1021/acs.jafc.2c06429. Epub 2022 Oct 13.

Abstract

Growing evidence for the importance of the gut-brain axis in Parkinson's disease (PD) has attracted researchers' interest in the possible application of microbiota-based treatment approaches. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, we looked into the prospect of treating PD with fucosylated chondroitin sulfate obtained from sea cucumbers Isostichopus badionotus (fCS-Ib). We showed that giving fCS-Ib polysaccharide orally greatly reduced the motor deficits, dopamine depletion, and alpha-synuclein increase caused by MPTP in the substantia nigra (SN). It appears that the anti-PD action of fCS-Ib polysaccharide could be attained by squelching inflammation. Glial cell hyperactivation in SN and overproduction of proinflammatory substances in serum could both be suppressed by fCS-Ib polysaccharide injection. The bacterial DNA in fresh colonic feces was submitted to 16S rRNA and untargeted metabolic analyses to confirm the participation of the microbiota-gut-brain axis in the aforementioned interpretation. The findings showed that the MPTP treatment-induced decrease in norank_f_Muribaculaceae and the increase in Staphylococcus were reversed by the administration of fCS-Ib polysaccharide. The NF-κB signaling pathway was shown to be involved in the fCS-Ib polysaccharide-induced anti-inflammation. In conclusion, our research demonstrated for the first time how fCS-Ib polysaccharide combats PD by reducing inflammation caused by gut microbial dysbiosis.

Keywords: Parkinson’s disease; gut microbiota; inflammation; sea cucumber fucosylated chondroitin sulfate.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Chondroitin Sulfates
  • DNA, Bacterial
  • Disease Models, Animal
  • Dopamine
  • Dysbiosis / drug therapy
  • Inflammation / drug therapy
  • Intestines
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B
  • Parkinson Disease* / etiology
  • Parkinson Disease* / genetics
  • Polysaccharides / pharmacology
  • RNA, Ribosomal, 16S
  • Sea Cucumbers*
  • alpha-Synuclein

Substances

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • alpha-Synuclein
  • Chondroitin Sulfates
  • DNA, Bacterial
  • Dopamine
  • fucosylated chondroitin sulfate
  • NF-kappa B
  • Polysaccharides
  • RNA, Ribosomal, 16S