Neuroprotective and Antioxidant Activities of Algerian Punica granatum L. Peel Extracts

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Background: Oxidative stress is implicated in many neurodegenerative disorders, such as Alzheimer’s disease. As an alternative, Punica granatum peels are widely used in the treatment of several ailments. To date, this is the first study on the anti-acetyl/butyrylcholinesterase effects of diethyl ether extract from Algerian pomegranate peels. Objective: This research aimed to evaluate the content of total phenolics, flavonoids, flavonols, and tannins in Punica granatum peel crude extract and its fraction diethyl ether, as well as to assess its antioxidant and neuroprotective activities. Methods: The total phenolic, flavonoid, flavonol, and tannin contents in the extracts were evaluated using spectrophotometric methods. The inhibitory effects on acetyl/butyrylcholinesterase were assessed using the in vitro models. In addition, several methods were used to investigate the antioxidant capacity of extracts, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline- 6-sulfonate) (ABTS) free radicals scavenging, phenanthroline, reducing power and cupric ion reducing antioxidant capacity (CUPRAC) assays. Results: Phytochemical analysis revealed that the diethyl ether extract recorded the highest content of total phenolics, flavonoids, flavonols, and tannins with values of 643.3 ± 9.96 μgGAE/mg, 78.97 ± 9.97 μgQE/mg, 31.32 ± 1.79 μgQE/mg and 96.6 ± 13.65 μgTAE/mg, respectively. Moreover, the diethyl ether extract exhibited the strongest activity in the DPPH scavenging assay (IC50=3.36 ± 0.11 μg/mL), ABTS scavenging assay (IC50=1.46 ± 0.10 μg/mL), CUPRAC assay (CA0.5=3.62 ± 0.36 μg/mL), phenanthroline assay (CA0.5=1.04 ± 0.10 μg/mL), reducing power assay (CA0.5=4.14 ± 0.32 μg/mL), antiacetylcholinesterase assay (IC50=114.86 ± 13.66μg/mL), and anti-butyrylcholinesterase assay (IC50=147.00 ± 10.41 μg/mL). Conclusion: The present study has shown the extracts from Punica granatum peel to be a rich source of bioactive compounds, potent antioxidants, and cholinesterase inhibitors. They could be considered as natural agents that can be used in anti-neurodegenerative pharmaceutical formulations