N-Acetyl cysteine together with rutin combats oxidative toxicity by modulating Nrf2 pathway in inflammatory brain–Liver axis in scopolamine-administered alzheimer&#039;s disease model in rats

Yongwei Shi; Yujie Yuan; Jing Li; Jun Shen; Qiangguo Ju; Shaoge Gao; Yuxiang Chen; Ibrahim Abdel Aziz Ibrahim; Petchi Iyappan; Ravindran Jaganathan

Articles

Abstract

Pharmacognosy Magazine,2022,18,80,1035-1044.

DOI:10.4103/pm.pm_108_22

Published:November 2022

Type:Original Article

Authors:

Author(s) affiliations:

Yongwei Shi¹, Yujie Yuan², Jing Li², Jun Shen¹, Qiangguo Ju¹, Shaoge Gao¹, Yuxiang Chen³, Ibrahim Abdel Aziz Ibrahim⁴, Petchi Iyappan⁵, Ravindran Jaganathan⁶
¹Department of Neurology, Taizhou Fourth People's Hospital, Taizhou, Jiangsu Province, 225300, China
²Department of Neurology, The Eighth People's Hospital of Hengshui, Hengshui, Hebei Province, 253800, China
³Department of Neurology, Chongqing Changshou District People's Hospital, Chongqing, 401220, China
⁴Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
⁵Faculty of Medicine, Bioscience and Nursing, School of Bioscience, MAHSA University, Saujana Putra 42610, Malaysia
⁶Microbiology Unit, Preclinical Department, Faculty of Medicine, Royal College of Medicine, Universiti Kuala Lumpur, Ipoh 30450, Perak, Malaysia

Abstract:

Background: Disruptive cholinergic neurotransmission and abnormal cognitive functions were the characteristics of Alzheimer's disease leading to abnormal brain–liver inflammatory responses. Oxidative stress was prominent in Alzheimer's disease-related neurodegeneration leading to inflammatory communication through altered cytokines between the brain and peripheral organs, mainly the liver. Objectives: Current study would demonstrate the healthier effect of N-acetyl cysteine and rutin against AD in rats. Materials and Methods: Experimental Wistar rats have been grouped appropriately for the administration of scopolamine and treatment using a combination of N-acetyl cysteine and rutin for 10 weeks. Results: In our study, scopolamine (2 mg/kg b.w.i.p.) administered Alzheimer's disease model in Wistar rats showed abnormality in behavioural changes (Morris water maze test), pro-inflammatory cytokines, decreased activities of enzymatic antioxidants, decreased reduced glutathione content, elevated brain oxidative stress markers, increased amyloid-beta, elevated acetylcholinesterase, elevated butyrl cholinesterase, increased phosphorylated tau protein, increased GSK-3β, BDNF, altered expressions of β-secretase, NADPH oxidase 2, and Nrf2 genes in brain, and augmented oxidative stress in liver affecting brain–liver axis. Oxidative stress in the liver was evident through decreased activities of enzymatic antioxidants, decreased glutathione content, and elevated liver oxidative stress markers. Conclusion: Treatment with N-acetyl cysteine with rutin showed protective efficacy by modulating the pathways related to Nrf2, NOX-2, and BACE1 genes in combating these abnormalities in rats. Modulation in the gene expressions in the brain tissue showed direct evidence of the drug's neuroprotective efficacy for future therapeutic strategies in scopolamine-induced Alzheimer's disease.