Therapeutic effects of a novel extract of Nerium Oleander in the Transgenic mouse model of Alzheimer's Disease

Alzheimer's disease (AD) can be characterized by the formation and progressive cerebral deposition of Amyloid beta plaques and neurofibrillary tangles, leading to loss of synapses and neuronal loss. Though the exact mechanism or cause of the disease is still unknown, constant efforts have been made to identify drugs that alleviate the symptoms and eliminate the progression of the disease. PBI-05204, the botanical extract of Nerium oleander and an anti-cancer drug has been previously reported to display neuroprotective activity and is mediated through the neurotrophic factor, BDNF (Brain derived neurotrophic factor) The suggested neuroprotective effects of PBI-05204 may potentially be mediated through Oleandrin, a component of PBI and exhibits anti-inflammatory and antioxidant properties. Giving the advantage of being a blood brain barrier penetrant among the other drugs that provide neuroprotection, it could be a potential therapeutic option for AD. The goal of this study is to analyze the therapeutic effects of PBI on neuropathological, neuroanatomical and neurochemical markers of Alzheimer's disease. The hallmarks of AD to be analyzed include the formation and progressive cerebral deposition of the amyloid β-protein (Aβ), activation of the glial cells surrounding amyloid, neuroinflammatory status and the antioxidant response. For this study, we use the APP/PSEN1 double transgenic mouse which expresses mutant human APP and mutant human PSEN1 (APPswe, PSEN1dE9). After administration of PBI-05204 or saline for four months to four-month-old APP/PSEN1 transgenic, the brain tissue were collected for further analysis. By methods of immunohistochemistry and western blotting, we found that on treatment with PBI-05204, there was an overall significant decline in the amyloid plaque accumulation and the expression of neuroinflammatory cell types, specifically microglia and astrocytes. The treatment with PBI-05204 also decreased the levels of Hemeoxygenase-1 antioxidant and induced protection to the cells against cell death and antioxidant stress. Hence PBI-05204 exhibits anti-inflammatory properties and aid decrease of the amyloid plaque pathology.