7,8-Dihydroxy-4-methylcoumarin Provides Neuroprotection by Increasing Hippocalcin Expression

Abstract

7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein that buffers intracellular calcium and prevents calcium-induced cell death. In our in vivo studies, Dhmc reduced infarct volume in neonatal rats when administered 4 h after cerebral hypoxia/ischemia injury and attenuated the hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal rats. Taken together, these results suggest that Dhmc prevents glutamate-induced toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc may represent a promising agent in the treatment of acute and chronic neurological disorders induced by oxidative stress.

Neurocalcin-delta: a potential memory-related factor in hippocampus of obese rats induced by high-fat diet.

“…Hpca is a protein that buffers intracellular calcium and prevents calcium-induced cell death 33 . A proteomic approach revealed that Hpca expression wasdecreased in vehicle-treated animals with combined middle cerebral artery occlusion 34 , indicating that its decline was likely to be the performance of damage/lesion.…”

Neuroprotective and Antioxidant Activities of 4-Methylcoumarins: Development of Structure–Activity Relationships

“…8,9,12,13) Since antioxidant agents may have great potential as neuroprotective compounds, in this study, we focused on the examination of the neuroprotective effect of previously synthesized 4-methylcoumarin derivatives in oxidative stress-induced neurotoxicity model in PC12 cells with a special focus on derivatives bearing 7,8-ortho-dihydroxy and 7,8-ortho-diacetoxy substitutions.…”

“…5,6) Antioxidant activities of various 4-methylcoumarin derivatives have been studied by our groups and other investigators [7][8][9][10][11] among which, 7,8-ortho-dihydroxy and 7,8-ortho-diacetoxy structures have shown promising effects in various test systems. 8,9,12,13) Since antioxidant agents may have great potential as neuroprotective compounds, in this study, we focused on the examination of the neuroprotective effect of previously synthesized 4-methylcoumarin derivatives in oxidative stress-induced neurotoxicity model in PC12 cells with a special focus on derivatives bearing 7,8-ortho-dihydroxy and 7,8-ortho-diacetoxy substitutions.…”

Behavioral, neuroplasticity and metabolic effects of 7,8-dihydroxy-4-methylcoumarin associated with physical activity in mice

“…It is considered a simple coumarin since structural substitution occurs only in the benzene ring using two hydroxyl radicals. In vitro studies have pointed to a possible neuroprotective effect of this coumarin, mainly related to its antioxidant and anti-in ammatory properties (Tyagi et al 2005;Togna et al 2014;Jin et al 2015). In the CNS coumarins seem to improve cell survival, promoting neuroprotection and promoting favorable conditions for neuronal expansion in mice and rats (Gao et Frequently these stimuli-induced neuroplasticity responses are mediated by trophic factors, such as ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) (Fabel et al 2003;Kokoeva et al 2007;Choi et…”