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Neuroinflammation has been closely linked to neurodegeneration that leads to dysfunction of memory and learning where glial fibrillary acidic protein plays important role within hippocampus. In experimental neurodegeneration achieved by two-vessel occlusion (2VO) intervention, Nigella sativa (L.) seeds extract (NSSE) has shown to have anti-neuroinflammatory and antioxidant properties. Toxic free radicals formation and prevention of neuroinflammatory mediators are of two possible mechanisms. The current study aimed to investigate the anti-neuroinflammatory effect of Nigella sativa and the role of GFAP as a relevant biomarker of neuroinflammation. The relative normalized hippocampal GFAP mRNA expressions (∆∆Cq) of Nigella sativa (L.) seeds extract treatment (100mg/kg/day orally) was compared with that of healthy control (HC) and untreated 2VO groups (n=6) of rats. The brain hippocampal tissues were humanely collected at the end of 10th treatment week and preserved in Allprotect™ reagent at – 80°C. Total RNA was extracted and purified by phenol/chloroform method using kits, and reverse transcribed into cDNA and relatively quantified as per ∆∆Cq. The NSSE treatment showed significantly (P<0.001) different relative GFAP mRNA expression in the treated group as compared to that of untreated 2VO whilst it was insignificantly (P>0.5) different to that of HC. Prolonged or daily treatment with NSSE may possess moderate anti-neuroprotective activity within hippocampus.