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

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Abstract

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.

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Acknowledgements

The acknowledgment expresses gratitude to the Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, for their essential support in facilitating the successful completion of work conducted at the Zebra Fish Laboratory. This support likely included providing the necessary infrastructure, and resources, which greatly contributed to the project's accomplishment. Sincere, appreciation is extended to the Drug Testing Laboratory at Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Saveetha University, for their contribution of vital equipment such as the fluorescent microscope and ELISA reader.

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  1. Praveen Kumar Issac and Kadhirmathiyan Velumani contributed equally.

Authors and Affiliations

  1. Institute of Biotechnology, Department of Medical Biotechnology and Integrative Physiology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, 602 105, Tamil Nadu, India

    Praveen Kumar Issac & Kadhirmathiyan Velumani

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  1. Praveen Kumar Issac
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Contributions

Conceptualisation, P.K.I. and K.V.; methodology, P.K.I; investigation, P.K.I. and K.V.; formal analysis, P.K.I. and K.V.; software, K.V.; writing—original draft, K.V.; writing—review and editing, P.K.I. and K.V.; visualisation, P.K.I. and K.V.

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Correspondence to Praveen Kumar Issac.

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The authors declare no competing interests.

Research Involving Humans and Animals Statement

All animal experiments were carried out following the ethical guidelines for the care and use of animals approved by the Institutional Ethical Committee (SU/CLAR/RD/001/2023).

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Highlights

• Gut dysbiosis will raise ROS level and leads to neurodegenerative diseases.

• Rutin trihydrate-conjugated zinc oxide nanoparticles (RTH-ZnO) were fabricated.

• RTH-ZnO inhibited the growth of gut dysbiosis-associated pathogens.

• RTH-ZnO scavenges free radicals and regulates stress-induced apoptosis.

• Improved cognitive behaviour was observed in the RTH-ZnO-treated group.

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Issac, P.K., Velumani, K. Rutin Trihydrate Conjugated Zinc Oxide Nanoparticles Targeting Oxidative Stress Pathways for the Protection of Gut Microbiome Dysfunction and Neurodegenerative Diseases. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01430-z

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