A natural product composition targeting oxidative stress induced mitochondrial dysfunction in Alzheimer's Disease

Abstract

Mitochondria regulates cellular metabolism and apoptosis. Oxidative stress induced mitochondrial dysfunction, appears to play a role in the pathogenesis of Alzheimer's disease. Natural antioxidants have been known to play an important role in alleviating the deleterious effects induced by free radicals by blocking the initiation and propagation of oxidizing chain reactions. Hence, the study hypothesizes the effect of natural product composition (combinatorial extract of Eclipta alba, Morinda pubescens and Withania somnifera) on restoring the mitochondrial functional capacity and mitochondrial enzyme levels. The individual and combinatorial methanolic extracts of dried whole plants of Eclipta alba (MEEA), dried fruits of Morinda pubescens (MEMP) and dried roots of Withania somnifera (MEWS) and MECE were prepared. The extracts were screened for in vitro antioxidant activity by DPPH assay. A rodent behavioural model to assess the effect of the extracts on short term memory was performed subsequent to scopolamine hydrobromide induced amnesia and oxidative stress. The brain homogenates from these rodents were subjected to screening in vivo antioxidaint activity using a battery of assays. The effect of extracts on restoring mitochondrial functional capacity (using MTT assay) and the levels of key mitochondrial enzymes succinate dehydrogenase and isocitrate dehydrogenase; was performed using synaptosomal fractions prepared from rodent brain samples.MEEA, MEMP, MEWS and MECE compared with ascorbic acid exhibited 50% scavenging effect at 69.34 μg/ml, 72.19 μg/ml, 65.84 μg/ml, 45.09μg/ml and 57.64 μg/ml, respectively by DPPH assay. Pretreatment with MEEA, MEMP and MEWS at the doses 50,100 and 200 mg/kg and MECE at 50 and 100mg/kg for 8 days followed by scopolamine hydrobromide treatment significantly (p<0.001) improved the antioxidant defense system, the mitochondrial functional capacity and mitochondrial enzyme levels.The natural product composition strengthened the endogenous antioxidant defense system, restored the mitochondrial functional capacity and enzyme levels. Hence, it has a potential neuroprotective role in Alzheimer's disease which needs to be investigated further in a clinical setting.Support or Funding InformationNMIMS UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.