Rutin Trihydrate Conjugated Zinc Oxide Nanoparticles Targeting Oxidative Stress Pathways for the Protection of Gut Microbiome Dysfunction and Neurodegenerative Diseases

Neurodegenerative diseases associated with gut dysbiosis are an important health concern, particularly reactive oxygen species (ROS) generation playing a critical role. However, therapeutic methods are hindered by the inadequate absorption of plant secondary metabolites into the brain. In our study, rutin trihydrate (RTH), a flavonoid, was used to synthesise rutin trihydrate-conjugated zinc oxide nanoparticles (RTH-ZnO) for addressing gut dysbiosis-generated ROS and its implications on neurodegeneration. We tested its antimicrobial properties against gut dysbiosis-associated pathogens and antioxidant activity against oxidative stress-induced zebrafish larvae. Our in vitro results indicated that the synthesised RTH-ZnO can efficiently scavenge free radicals and maintain redox homeostasis. The zebrafish developmental toxicity analysis does not reveal any lethal malformation in the RTH-ZnO-treated group with an increased survival rate. RTH-ZnO potentially regulated the intercellular reactive oxygen species (ROS) and stress-induced apoptosis in the larvae exposed to H₂O₂. Notably, cognitive functions were also improved with increased acetylcholinesterase (AChE) and antioxidant gene expression. In conclusion, our study supports the potential of RTH-ZnO nanoparticles to treat gut dysbiosis-generated ROS-induced neurodegeneration.