Bidirectional effect of Triphala on modulating Gut-brain axis to improve cognition in the Murine Model of Alzheimer’s disease

Abstract

Background The emerging role of gut microbiota and their metabolites in the modulation of the gut-brain axis has received much attention as a new hope for the treatment of hard-to-treat chronic neurodegenerative diseases like Alzheimer’s Disease. The naturally occurring polyphenols can restore the gut-brain axis by modulating gut microbiota and brain neurotransmitters. However, the mechanism of action remained unclear. The Indian traditional medicine Triphala, a rich source of polyphenols, has been used on humans based on Prakriti or disease conditions for many years. Methods: In this study, the dual mode (morning and evening) action of Triphala was used to provide scientific evidence of its superior preventive and therapeutic efficacy in C57BL/6 and 5xFAD, APP/PS1 transgenic mouse model of Alzheimer’s disease. For behavior analysis, used the Morris water model and Y maze model to assess spatial memory and exploratory behavior. The blood serum and brain lysate were used to evaluate the inflammatory activity and oxidative parameters in the mice. The gut microbiome analysis was done by 16srRNA analysis from mice feces after 60 days of treatment. Results We observed that Triphala treatment has significantly improved cognitive function, by modulating the APP pathway, reducing inflammation, oxidative stress, and restoring the gut-brain axis by increasing the gut microbiota phyla of Bacteroides, Proteobacteria, Actinobacteria, etc., involved in maintaining the gut homeostasis. Conclusions Our study paved a new path for using dual modes of Triphala one or in combination to treat incurable AD.