Methods and related compositions for reducing oxidative stress

#The present disclosure relates to methods and related compositions for reducing oxidative stress. Specifically, the one embodiment of the present disclosure reduces the oxidative stress of a mammal by administering the mammal with Baillonella toxisperma extract which provides a variety of benefits, including but not limited to reducing free radicals and protecting neurons of a mammal, which in turn allows the prevention and treatment of Alzheimer's and Parkinson's disease.

#Oxidative stress is the disturbance of the intracellular oxidative status; either by the excessive production of free radicals or by a reduction of the antioxidant defense capacity (Morel et al., 1999). It is implicated in pathologies such as Cardiovascular Disease (CVD), certain cancers, cutaneous aging and neurodegenerative diseases (Morel et al., 1999). Oxidative stress is considered as a major risk factor in the incidence and progression of cognitive decline which usually occurs during normal cerebral aging and plays a critical role in a variety of neurodegenerative processes such as Alzheimer's and Parkinson's diseases (Butterfield et al., 1999). Recent data show that oxidative stress is one of the primordial events involved in the pathogenesis of Alzheimer's disease, where it is implicated in excitotoxicity (a major cause of the death of neurons) (Nunomura et al., 2001).

#Many factors such as metabolic disturbances, inflammation, physical agents, cytokines, presence of oxygenated oxidants, oxidative phosphorylation etc. can lead to the production of free radicals (Morel et al., 1999). Free radicals react with oxidisable substrate (i.e. oxygen) and produce carbonyl radicals. The latter have multiple intracellular effects amongst which are glycation of proteins, alteration of DNA structure, generation of products of lipid peroxidation and the modulation of the transcription of numerous genes. The amount of reactive oxygen species is produced in any tissue is directly proportional to its rate of oxygen consumption. The effects of the latter production could accumulate in neurons for years (Nunomura et al., 2001). The brain with its high energy consumption rate is constantly undergoing the oxidation/antioxidation process which makes it highly stress sensitive (Ikonomidou et al., 2011), especially as this process is amplified by intellectual activities such as thinking and reasoning. The antioxidant defense mechanism of the brain traps free radicals and reduces damages which they could cause, but this mechanism cannot always be efficient. This efficiency discrepancy is exacerbated especially when the concentration of reactive oxygen species (ROS) becomes too high, or when the concentration of antioxidants becomes too low. This provokes the destruction of macromolecules such as DNA, lipids, proteins; and eventually the death of the cell by apoptosis and/or necrosis which could lead to many neurological, motor and cognitive inconsistencies and worst still, neurodegenerative disorders of which Alzheimer's (incurable) is the leading disease. (Halliwell and Gutteridge, 1999; Halliwell, 2012). Thus improving cell antioxidant status or reducing its rate of free radical production could be an effective strategy to protect neurons from oxidative damages and therefore prevent the initiation and progression of Alzheimer's disease (Simonian et al., 1996, Mangialasche et al., 2010).

#FIG. 1 shows extraction protocol for phenolic compound in B. toxisperma in accordance with one embodiment of the present disclosure.

#FIG. 2 shows protocol for fractionation of flavonoids in B. toxisperma in accordance with one embodiment of the present disclosure.

#FIG. 3 shows total antioxidant capacity of aqueous, ethanolic and hydroethanolic extracts of B. toxisperma in accordance with one embodiment of the present disclosure.

#The following description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention. Various inventive features are described below that can each be used independently of one another or in combination with other features.

#Broadly, embodiments of the present invention generally relates using extracts and flavonoid fractions obtained from the bark of Baillonella toxisperma to protect neurons from oxidative stress and provide benefits as an antioxidant.

#In one aspect of the present disclosure, the antioxidant and neuroprotective effects of the bark of Baillonella toxisperma on in vivo and in vitro neuro-toxicity models associated to oxidative stress was evaluated. In another aspect of the present disclosure, the effects of extracts and flavonoid fractions of Baillonella toxisperma on in vivo and in vitro neuro-toxicity models associated to oxidative stress was evaluated. Specific objectives of the present disclosure further includes evaluating the contents of bioactive compounds in aqueous, ethanolic and hydroethanolic extracts of the bark of Baillonella toxisperma as well as their in vitro antioxidant potential; evaluating the neuroprotective effects of the extract with the best in vitro anti-oxidative potential; against neurotoxicity induced by the administration of a single dose of Aluminum in Wistar rats and measurement of some markers of oxidative stress; and extracting flavonoid fractions of the bark of Baillonella toxisperma from its methanolic extract and compare the effectiveness of this extract with those of the fractions; in reducing the production of reactive oxygen species induced by hydrogen peroxide in human SK-N-SH neuroblastome cells.