Anti-Alzheimer potential of a waste by-product (peel) of Omani pomegranate fruits: Quantification of phenolic compounds, in-vitro antioxidant, anti-cholinesterase and in-silico studies

Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease. Punica granatum L., (P. granatum) is one of the most important commercial crops of Oman with traditional medicinal claims. The study aimed to quantify the phenolic content of the Omani pomegranate peel extracts and to investigate their antioxidant, anti-cholinesterase activities along with computational studies for the development of AD therapy. The dried peels of P. granatum fruits were exhaustively extracted with chloroform, ethyl acetate and butanol. Peel extracts were subjected to the preliminary phytochemical screening. Colorimetric methods were used to quantify total phenolic and flavonoids contents. The neuroprotective potential of the peel extracts was evaluated by assessing the in-vitro antioxidant activity and their ability to inhibit acetylcholinesterase (AChE) enzyme activity. In-silico analysis and molecular docking of the most promising phenolic metabolite present in pomegranate peel was also carried out. The phytochemical screening showed the presence of flavonoids, tannins, alkaloids, carbohydrates and terpenoids. The total phenolic, flavonoids content & antioxidant activity was found to be higher in the butanol extract. Surprisingly, butanol extract showed slightly lower AChE inhibitory activity than chloroform extract. Catechin, a polyphenolic compound present in the peel showed lower binding energy for AChE in comparison to Beta-secretase-1 (BACE-1). It formed three and two hydrogen bonds with AChE and BACE-1, respectively. The results of the current study provided evidence that butanol extract is rich in phenolics and possesses excellent antioxidant activity. Furthermore, in silico and in-vitro studies conducted on P. granatum revealed promising anti-AD activity. Further investigations must be carried out to isolate and develop the chemical constituents of pomegranate peel as neuroprotective agent(s).