Abstract
Ginkgo biloba, a natural biflavonoid isolated from Ginkgo biloba leaves, is reported to have strong anti-inflammatory and immunosuppressive properties. The aim of this study is to investigate the potential anti-inflammatory mechanisms of ginkgo flavonoids on cerebral ischemia/reperfusion (I/R) injury. Inflammatory-associated cytokines in cerebral ischemic hemispheres were determined by immunohistochemical staining, Western blot and enzyme-like immunosorbent assay (ELISA). Our results indicated that treatment with Ginkgetin significantly restored rat brain I/R-induced neurological deficit scores. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in Ginkgetin treatment group (100 mg/kg) also significantly reduced. The expression inflammation-related protein prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-8 (IL-8) was also decreased in Ginkgetin treatment group. However, the expression of interleukin-10 (IL-10) was remarkably increased. Thus, this study demonstrates that Ginkgetin protects neurons from I/R-induced rat injury by down-regulating pro-inflammatory cytokines and blocking the TLR4/NF-κB pathway.
Keywords:
Ginkgetin; Ginkgo flavonoid; TLR4/NF-κB; anti-inflammatory; cerebral ischemia/reperfusion (I/R) injury.
MeSH terms
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Animals
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Anti-Inflammatory Agents / isolation & purification
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Anti-Inflammatory Agents / pharmacology*
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Biflavonoids / isolation & purification
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Biflavonoids / pharmacology*
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Brain Ischemia / drug therapy*
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Brain Ischemia / genetics
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Brain Ischemia / immunology
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Brain Ischemia / pathology
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / immunology
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Dinoprostone / genetics
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Dinoprostone / immunology
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Disease Models, Animal
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Drug Administration Schedule
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Gene Expression Regulation / drug effects*
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Ginkgo biloba / chemistry*
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Interleukin-10 / genetics
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Interleukin-10 / immunology
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Interleukin-1beta / genetics
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Interleukin-1beta / immunology
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Interleukin-8 / genetics
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Interleukin-8 / immunology
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Male
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NF-kappa B / genetics
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NF-kappa B / immunology
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Neuroprotective Agents / isolation & purification
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Neuroprotective Agents / pharmacology*
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / immunology
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Plant Extracts / chemistry
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Rats
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Rats, Sprague-Dawley
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Reperfusion Injury / drug therapy*
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Reperfusion Injury / genetics
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Reperfusion Injury / immunology
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Reperfusion Injury / pathology
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Signal Transduction
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Toll-Like Receptor 4 / genetics
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Toll-Like Receptor 4 / immunology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Anti-Inflammatory Agents
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Biflavonoids
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IL1B protein, rat
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Il6 protein, rat
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Interleukin-1beta
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Interleukin-6
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Interleukin-8
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NF-kappa B
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Neuroprotective Agents
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Plant Extracts
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Tlr4 protein, rat
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Toll-Like Receptor 4
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Tumor Necrosis Factor-alpha
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Interleukin-10
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ginkgetin
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Nitric Oxide Synthase Type II
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Nos2 protein, rat
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Cyclooxygenase 2
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Ptgs2 protein, rat
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Dinoprostone