Abstract
Herein, we have evaluated the protective potentials of Fisetin against d-galactose-induced oxidative stress, neuroinflammation, and memory impairment in mice. d-galactose (D-gal) causes neurological impairment by inducing reactive oxygen species (ROS), neuroinflammation, and synaptic dysfunction, whereas fisetin (Fis) is a natural flavonoid having potential antioxidant effects, and has been used against different models of neurodegenerative diseases. Here, the normal mice were injected with D-gal (100 mg/kg/day for 60 days) and fisetin (20 mg/kg/day for 30 days). To elucidate the protective effects of fisetin against d-galactose induced oxidative stress-mediated neuroinflammation, we conducted western blotting, biochemical, behavioral, and immunofluorescence analyses. According to our findings, D-gal induced oxidative stress, neuroinflammation, synaptic dysfunctions, and cognitive impairment. Conversely, Fisetin prevented the D-gal-mediated ROS accumulation, by regulating the endogenous anti-oxidant mechanisms, such as Sirt1/Nrf2 signaling, suppressed the activated p-JNK/NF-kB pathway, and its downstream targets, such as inflammatory cytokines. Hence, our results together with the previous reports suggest that Fisetin may be beneficial in age-related neurological disorders.
Highlights
Aging is a cause of several chronic diseases, including diabetes mellitus, cardiovascular diseases, cancer, and neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) (Khan et al, 2018)
To analyze the antioxidant effects of Fisetin, we performed the reactive oxygen species (ROS) and LPO assays, which showed that D-gal increased the levels of LPO and ROS, which were partially reduced with the administration of Fisetin (Figures 2A,B)
These results were further confirmed with the immunofluorescence analysis, which showed that Fisetin significantly enhanced the expression of silent information regulator transcript-1 (SIRT1) and Nuclear factor erythroid 2-related factor 2 (Nrf-2) in the Fisetin-treated mice brains (Figures 2D,E)
Summary
Aging is a cause of several chronic diseases, including diabetes mellitus, cardiovascular diseases, cancer, and neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) (Khan et al, 2018). Several studies have indicated that elevated ROS level is responsible for different neurodegenerative conditions in various age-associated disorders such as AD, PD, and diabetes (Olanow, 1993; Khan et al, 2019a). The elevated oxidative stress triggers cellular damage to the macromolecules (proteins, lipids, and DNA), which disturbs the physiological functions of the central nervous system (CNS), leading to neurodegeneration (Paradies et al, 2011). The neurodegeneration caused by elevated oxidative stress could be a therapeutic target to tackle age-related diseases neurodegenerative diseases. To develop neuroprotective strategies against age-related neurological disease, different animal models have been developed. One of the known models is the D-gal injected animal model
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