Neuroprotective effect and antioxidant activity of Passiflora edulis fruit flavonoid fraction, aqueous extract, and juice in aluminum chloride-induced Alzheimer’s disease rats

Abstract

Background: Oxidative stress is known to contribute to the mechanisms underpinning the pathogenesis of neurodegenerative diseases. Previous studies have identified the presence of flavonoids as the major constituents of Passiflora edulis (PE) with antioxidant activity. This work aims at investigating the antioxidant, anti-neuroinflammatory, and neuroprotective effect of three PE fruit extracts, flavonoid fraction, and juice on neurodegenerative rat model. Methods: Extracts were prepared using fruit pulp and peel and juice using pulp. Phytochemical contents (phenolic content and flavonoid) and in vitro antioxidant activity were evaluated through the DPPH radical scavenging capacity and the ability to reduce ferric ion. The neurocognitive dysfunction, activity of acetylcholinesterase (AChE), levels and activities of in vivo oxidant–antioxidant indices as well as neuroinflammatory markers were evaluated in the hippocampus and cortex of aluminum chloride (AlCl3) induced Alzheimer’s rats (AD). Results: The highest total phenolic and flavonoids’ contents, the best DPPH scavenging activity and the ability to reduce ferric ion (Fe3+) were obtained with peel aqueous extract. The administration of the peel aqueous extract, juice, and flavonoid fraction resulted in a significant decrease (P < 0.05) in plasma and tissue levels of malondialdehyde compared to the positive control (PC). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cycyclooxygenase-2 (COX-2), and amyloid ß-42 (ß-42) were significantly reduced whereas the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione level were significantly higher in the treated than that in the untreated Alzheimer’s rats (PC) groups (P < 0.05), respectively, in the hippocampus and in plasma, brain, and liver homogenates following the administration of juice, flavonoid fraction, and extracts (both doses). Treatment of AD-rats with PE ameliorated neurobehavioral changes, as evidenced by the improvement in brain function, as well as, modulation of AChE, and confirmed by the histological changes and Morris water maze test. The effect of aqueous extract was slightly greater than that of the flavonoids fraction, thus suggesting that flavonoids account for most of the Passiflora edulis antioxidant activity and neuroprotective effect.