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Open AccessArticle

Phytomedicine-Based Potent Antioxidant, Fisetin Protects CNS-Insult LPS-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment

Division of Applied Life Science (BK 21), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(6), 850; https://doi.org/10.3390/jcm8060850
Received: 16 May 2019 / Revised: 5 June 2019 / Accepted: 11 June 2019 / Published: 14 June 2019
Phytomedicine based natural flavonoids have potent antioxidant, anti-inflammatory, and neuroprotective activities against neurodegenerative diseases. The aim of the present study is to investigate the potent neuroprotective and antioxidant potential effects of fisetin (natural flavonoid) against central nervous system (CNS)-insult, lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), neuroinflammation, neurodegeneration, and synaptic/memory deficits in adult mice. The mice were injected intraperitoneally (i.p.) with LPS (250 μg/kg/day for 1 week) and a fisetin dosage regimen (20 mg/kg/day i.p. for 2 weeks, 1 week pre-treated to LPS and 1 week co-treated with LPS). Behavioral tests, and biochemical and immunofluorescence assays were applied. Our results revealed that fisetin markedly abrogated the LPS-induced elevated ROS/oxidative stress and activated phosphorylated c-JUN N-terminal Kinase (p-JNK) in the adult mouse hippocampus. Fisetin significantly alleviated LPS-induced activated gliosis. Moreover, fisetin treatment inhibited LPS-induced activation of the inflammatory Toll-like Receptors (TLR4)/cluster of differentiation 14 (CD14)/phospho-nuclear factor kappa (NF-κB) signaling and attenuated other inflammatory mediators (tumor necrosis factor-α (TNF-α), interleukin-1 β (IL1-β), and cyclooxygenase (COX-2). Furthermore, immunoblotting and immunohistochemical results revealed that fisetin significantly reversed LPS-induced apoptotic neurodegeneration. Fisetin improved the hippocampal-dependent synaptic and memory functions in LPS-treated adult mice. In summary, our results strongly recommend that fisetin, a natural potent antioxidant, and neuroprotective phytomedicine, represents a promising, valuable, and therapeutic candidate for the prevention and treatment of neurodegenerative diseases. View Full-Text
Keywords: phytomedicine; natural flavonoids; fisetin; central nervous system (CNS) insult; lipopolysaccharide (LPS); oxidative stress; neuroinflammation; neurodegeneration; synaptic and memory functions phytomedicine; natural flavonoids; fisetin; central nervous system (CNS) insult; lipopolysaccharide (LPS); oxidative stress; neuroinflammation; neurodegeneration; synaptic and memory functions
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Ahmad, A.; Ali, T.; Rehman, S.U.; Kim, M.O. Phytomedicine-Based Potent Antioxidant, Fisetin Protects CNS-Insult LPS-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment. J. Clin. Med. 2019, 8, 850.

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