کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2536841 1559168 2006 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of nuclear factor κB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Inhibition of nuclear factor κB is associated with neuroprotective effects of glycyrrhizic acid on glutamate-induced excitotoxicity in primary neurons
چکیده انگلیسی

Glycyrrhizic acid is an herbal drug with a broad spectrum of antiviral activities and pharmacological effects and multiple sites of action. We investigated whether glycyrrhizic acid protects against glutamate-induced excitotoxicity and the underlying mechanisms. We found that glycyrrhizic acid protected against neurotoxicity in rat primary neuronal cultures and hippocampal slices by suppression of the glutamate-induced apoptosis. Glycyrrhizic acid conferred neuroprotective properties in a concentration-dependent manner, as determined by cell survival, apoptosis, and Ca2+ influx. Glycyrrhizic acid selectively inhibited the Ca2+ influx activated through N-methyl-d-aspartate (NMDA) receptor by glutamate, but not through membrane depolarization elicited by high K+ induction. Glycyrrhizic acid treatment also diminished glutamate-induced DNA fragmentation and cleavage of poly (ADP-ribose) polymerase (PARP). Electrophoretic mobility shift assay (EMSA) indicated that glycyrrhizic acid inhibited the binding activity of nuclear factor κB (NF-κB) to its target elements. Western blot analysis of NF-κB inhibitor (IκBα) protein revealed that the inhibitory effect of glycyrrhizic acid on glutamate-induced activation of NF-κB activity was attributable to the inhibition of IκB kinase activity. Thus, the site of action of glycyrrhizic acid could be a downstream consequence of Ca2+entry through NMDA receptors and that NF-κB may be one downstream target in this process. These observations suggest that glycyrrhizic acid may be of therapeutic value for the prevention of cerebral damage elicited by the glutamate.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 547, Issues 1–3, 10 October 2006, Pages 10–21
نویسندگان
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