Bio-guided isolation of anti-Alzheimer’s compounds from Phyllanthus niruri and role of niruriflavone in the reversal of aluminum chloride-induced neurobehavioral and biochemical changes in an animal model

Alzheimer’s disease (AD) is one of the chronic neurodegenerative pathologies that lead to memory loss and mental and behavioral changes in elderly people. The senile plaques, neurofibrillary tangles, oxidative stress, increased acetylcholinesterase (AChE), and neuroinflammation by activating 5-lipoxygenases (5-LOX) are important pathological processes in AD. Phyllanthus niruri Linn (PN) earned a lot of attention for phytoconstituents and their medicinal properties. The compounds quercitrin and niruriflavone were isolated by bio-guided fractionation from PN using the in vitro assays. Both compounds showed good docking scores on AChE and 5-LOX targets in the molecular docking studies. AD was induced in rats by 100 mg/kg of oral aluminum chloride (AlCl 3 ) for 42 days. It decreased the antioxidative enzymes and increased lipid peroxidation and AChE activity. Oral administration of niruriflavone reversed the neurobehavioral changes caused by AlCl 3 . The niruriflavone treatment also restored the antioxidative enzymes and attenuated the AChE and lipid peroxidation. All the evidence suggests that isolated compounds could benefit the population afflicted by AD in a multitargeted manner. Graphical abstract