Allantoin ameliorates dopaminergic neuronal damage in MPTP-induced Parkinson's disease mice via regulating oxidative damage, inflammation, and gut microbiota disorder

Aug 27, 2024Food & function

Allantoin reduces dopamine neuron damage in Parkinson’s model mice by controlling oxidative stress, inflammation, and gut bacteria imbalance

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Abstract

Allantoin administration improved motor function and reduced neuronal damage in mice with Parkinson's disease induced by MPTP.

Allantoin may reduce neuroinflammation and oxidative damage associated with Parkinson's disease.
The compound appears to inhibit inflammatory responses by affecting specific signaling pathways (NF-κB and MAPK).
Allantoin is associated with the modulation of oxidative stress through the AKT/Nrf2/HO-1 signaling pathway.
There is a potential improvement in intestinal barrier function linked to Allantoin's effects on gut microbiota.
The findings suggest that Allantoin could alleviate motor deficits related to MPTP-induced Parkinson's disease.

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Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that often occurs in older people. Neuroinflammation and oxidative stress are important factors in the development of PD. Gastrointestinal dysfunction is the most common non-motor symptom, and inflammation of the gut, which activates the gut-brain axis, maybe a pathogenic factor. Previous studies have attributed anti-inflammatory and antioxidant effects to Allantoin, but its function and mechanism of action in PD are unclear. This study aimed to investigate the effect and mechanism of Allantoin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice. Our results showed that Allantoin administration ameliorated motor dysfunction and neuronal damage in mice injected with MPTP by inhibiting neuroinflammation and oxidative damage. Mechanistic studies showed that Allantoin suppresses inflammatory responses by inhibiting the overactivation of the NF-κB and MAPK signaling pathways, as well as oxidative stress by regulating the AKT/Nrf2/HO-1 signaling pathway. Notably, Allantoin also restored intestinal barrier function by modulating the gut microbiota and improving antioxidant and anti-inflammatory capacities to alleviate MPTP-induced motor deficits. In conclusion, the present study shows that the administration of Allantoin attenuated neurodegeneration in mice injected with MPTP by inhibiting neuroinflammation and oxidative stress and modulating the composition of the gut microbiome.

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