Dementia is a clinical syndrome involving the loss of cognitive and social functions and to cause significant impairment in daily life. The most common type of dementia is Alzheimer's disease (AD) in which amyloid beta (Aβ) and neurofibrillary tangles are major pathological changes, causing oxidative stress and triggering inflammation process in central nervous system neurons.1 In addition, the activity of endogenous antioxidant enzymes are decreased in patients with AD.2 (Aβ) inhibits enzymes in the brain and mitochondria especially cytochrome c oxidase. Mitochondrial dysfunction together with lower activity of antioxidative enzymes trigger oxidative stress. Oxidative damage is associated with the release of proinflammatory cytokines and irreversible DNA damage.3
Alzheimer's dementia is associated with the loss of cholinergic neurons that produce acetylcholine and most licensed drugs that act as cholinesterase inhibitors which increase acetylcholine levels at the synapse are alkaloid-based drugs derived from phytochemicals, such as galantamine and rivastigmine. The use of these natural sources in the development of medicines sets a precedent for extensive research on plant-derived medicines.4 In addition, phytochemicals are less toxic than synthetic drugs and offer a more reliable alternative.5 Polyphenols are compounds that make up one of the broadest categories of phytochemicals are essential in human life.6 Flavonoids are a subclass of polyphenols and are divided into 6 subgroups: anthocyanins, flavanols, flavanones, flavones, flavanols, and isoflavones. Anthocyanins, a subclass of flavonoids from polyphenolic compounds, are abundant in various flowers, leaves, seeds, and fruits, such as berries6. Anthocyanins have attracted a lot of attention because of their neuroprotective effects on the central nervous system.7 Anthocyanins may ameliorate many of the deleterious effects of processes involved in neurodegeneration, such as oxidative and nitrosative stress, excitotoxicity, glial inflammation, protein aggregation, and induction of apoptotic signaling proteins.8
Mulberry is a tree species belonging to the Morus genus from the mulberry family (Moraceae). The three most common species are white mulberry (Morus alba L.), red mulberry (M. Rubra L.), and black mulberry (M. nigra L.). Phenolic acids, flavonoids, and anthocyanin-structured compounds are the main bioactive components found in Morus nigra plant.9
Phenolic components found in its fruits are chlorogenic acid and rutin.10 Cyanidin-3 glycoside, cyanidin-3 rutinoside, pelargonidin-3 glycoside and pelargonidin-3 rutinoside are found as anthocyanin derivatives from flavonoids.11 Mulberry fruits contain about 43% more phenolic compounds and approximately 50% more anthocyanins than blueberry fruits.12 In addition, black mulberry contains more anthocyanins than blackberries and currants.13 Significant improvements in cognitive functions were seen in individuals with mild cognitive impairment in both clinical studies with blueberry juice and grape juice.14,15 The purpose of this study was to test the feasibility and possible effects of black mulberry intervention on cognitive function and complete blood count in patients with AD. Therefore, we hypothesized that black mulberry consumption improves Mini-Mental State Examination (MMSE) and AD Assessment Scale–Cognitive Subscale (ADAS-Cog) scores in individuals in the early stages of dementia.
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