title: Protection of MPTP-induced neuroinflammation and neurodegeneration by Pycnogenol.
abstract: Oxidative stress and inflammation play a crucial role in Parkinson's disease (PD) pathogenesis and may represent a target for treatment. Current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Flavonoids have been suggested to exert human health benefits by its anti-oxidant and anti-inflammatory properties. Therefore, in the present study, using 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-induced mouse model of Parkinsonism, we investigated the neuroprotective potential of bioflavonoid compound Pycnogenol® (PYC), an extract of Pinus maritime bark. MPTP injected mice developed significantly severe oxidative stress and impaired motor coordination at day 1 and day 7 postinjection. This was associated with significantly increased inflammatory responses of astrocyte and microglia as assessed by ionized calcium binding adaptor molecule 1 (Iba 1) and glial fibrillary acidic protein (GFAP) immunohistochemistry, and nuclear transcription factor-κB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the striata by Western blot. Additionally, there was significant upregulation of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) expression in the striata of MPTP injected mice compared to saline controls. The MPTP-induced neuroinflammation, neurodegeneration and behavioral impairments were markedly repudiated by treatment with PYC. These results suggest that PYC protects dopaminergic neurons from MPTP-induced toxicity in the mouse model of PD. Thus, the present finding of PYC-induced adaptation to oxidative stress and inflammation could suggest a novel avenue for clinical intervention in neurodegenerative diseases including PD.
authors: Department of Neurology, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA. mohammad-khan@uiowa.edu
authors: Mohammad Moshahid
authors: MM
authors: Khan
authors: Duraisamy
authors: D
authors: Kempuraj
authors: Ramasamy
authors: R
authors: Thangavel
authors: Asgar
authors: A
authors: Zaheer
mesh_terms: D000818:Animals; D005419:Flavonoids / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D020267:MPTP Poisoning / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010300:Parkinson Disease / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010936:Plant Extracts
chemical_list: D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; C024070:pycnogenols
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