Effects of garcinol on free radical generation and NO production in embryonic rat cortical neurons and astrocytes.
Garcinol (camboginol) is a polyisoprenylated benzophenone derivative isolated from fruit rind of Garcinia indica. This study was to elucidate the anti-oxidative and neuroprotective properties of garcinol in rat cortical neuron cultures. First, garcinol protects DNA from Fenton reaction-induced breakage in a dose-dependent manner, with an IC(50) value of 0.32 microM. Garcinol also inhibits xanthine oxidase activity with an IC(50) value of 52 microM and exhibits competitive inhibition. To further ascertain the neuroprotective effects of garcinol in inflammatory-mediated neurotoxicity, we utilized primary neuron/astrocyte co-cultures treated with LPS or cytokine. Our data implicate that treatment with garcinol (5 microM) for 7 days promotes neuronal attachment and neurite extension. The formation of nitric oxide (NO) by LPS in rat astrocytes has been suggested to correlate with the neurodegenerative process. In identifying the effect of neuroprotection, we found that garcinol prevented NO accumulation in LPS-treated astrocytes. Garcinol significantly reduced the expression of LPS-induced inflammatory mediators, such as iNOS and COX-2. Consequently, our results suggest that the neuroprotective effects of garcinol are associated with anti-oxidation and inhibition of iNOS induction in astrocytic cells. Garcinol may exert a similar anti-inflammatory effect and may be neuroprotective against brain injury.
Liao
Chiung-Ho
CH
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ho
Chi-Tang
CT
Lin
Jen-Kun
JK
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D013729:Terpenes / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D004791:Enzyme Inhibitors; D005609:Free Radicals; D008070:Lipopolysaccharides; D013729:Terpenes; D009569:Nitric Oxide; D017665:Hydroxyl Radical; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D014969:Xanthine Oxidase; C054597:garcinol