Exploiting Citrus aurantium seeds and their secondary metabolites in the management of Alzheimer disease

Abstract

Fruit by-products are considered nature's golden gift for human health and a good starting point to discover new drugs depending on the fact that they contain millions of bio-active compounds that are responsible for therapeutic activities. In this context, the main goal of this study is to recycle Citrus aurantium (C. aurantium) seeds to produce pharmaceutical molecules to be used in the prevention of the progressive neurological damage associated with Alzheimer disease (AD). Donepezil (0.75 mg/kg), hesperidin (125 and 250 mg/kg) and limonoids (50 and 100 mg/kg) were used for treatment of rats for 2 weeks prior to concomitant administration of AlCl₃ for three successive weeks. Protection against cognitive deterioration was observed among study group with insignificant difference from normal control group and significant difference from positive control group in the Y-Maze test. On the other hand, treatment with both doses of hesperidin (125 and 250 mg/kg) and high dose of limonoids only (100 mg/kg) produced improvement in psychological state, observed by significant increase in ambulation frequency in comparison to positive control group, however it was not as frequent as normal group, as it was significantly less than normal group in the open field test. Regarding acetylcholine esterase (AChE) and beta-amyloid (β amyloid) levels, the effect of limonoids low dose was the best as it didn't have a significant effect when compared to normal control, also hesperidin in both doses showed insignificant effects on β amyloid levels when compared to normal control group. Our results encourage the use of C. aurantium seeds which are wasted in huge amounts, as Alzheimer prophylactic food additives.

Keywords: Acetylcholine esterase; Alzheimer disease; Beta-Amyloid protein; Citrus aurantium seeds; Flavonoids; Lemonoids; Open field; Tau protein; Y-Maze.

Graphical abstract

Fig. 1

Structure of spontaneous alternation of Y maze apparatus.

Fig. 2

(1): A Photomicrograph of a section showing the normal control cerebral cortex of adult rats with the molecular layer containing nuclei of neuroglial cells, the granular layer containing numerous granular cells with rounded open face nuclei (black arrow) and small pyramidal cells with short apical dendrites (blue arrow) (H&E×400). (2): A Photomicrograph of a section of cerebral cortex of the donepezil (0.75 mg/kg) treated rats showing nearly normal neuronal cells (H&E×400). (3): A Photomicrograph of the cerebral cortex of the AlCl₃ treated rats showing cellular vascular degeneration, atrophy, pyknosis, necrosis, neurology, congestion of cerebral blood vessels and focal cerebral haemorrhage (H&E×400). (4): Photomicrograph of the cortex of rat treated with low dose of limonoid showing marked improvement in most of the granule cells while the pyramidal are shown to be irregular in shape and surrounded by pericellular halos (H&E ×400). (5): A Photomicrograph of the cortex of rats treated with high dose of limonoid showing prominent regeneration where molecular layer contain nuclei of neuroglia cells and are covered with pia mater, and the granular layer contains numerous granular cells with rounded open face nuclei (H&E ×400).(6): A Photomicrograph of the cortex of rats treated with a low dose of hesperidin showing more or less improvement in granular cells and focal celluar pyknosis (H&E×400).(7): A Photomicrograph of the cortex of rats treated with a high dose of hesperidin showing nearly normal granular cells and neural structure (H&E ×400).