Multitarget pharmacological effects of Lawsone in mitigating Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive neuronal loss, cognitive impairment, oxidative stress, neuroinflammation, and aggregation of abnormal proteins, including amyloid precursor protein (APP), amyloid-beta (Aβ), and hyper phosphorylated Tau (p-Tau). Developing therapies that simultaneously target multiple pathogenic pathways remains a major therapeutic challenge. Lawsone (LW), a naturally occurring naphthoquinone derived from the leaf of henna plant (Lawsonia inermis), was investigated for its therapeutic potential in AD. Computational studies were performed to evaluate binding affinities and stability of the compound against key AD-related molecular targets. Sprague-Dawley rats were randomly assigned to five groups: vehicle control, Scopolamine (SCP), donepezil (DNZ), and two groups treated with LW at doses of 2.5 and 5 mg/kg. Morris water Maze and Y Maze tests were employed to validate the behavioral performance. Oxidative stress markers were measured biochemically, tissue histopathology was evaluated using hematoxylin-eosin and Congo red staining. Expression of the proinflamatory markers, nuclear factor kappa β (NF-κβ), c-Jun N terminal kinase (c-JNK), Tumor necrosis factor-α (TNF-α) and Alzheimer's associated proteins APP, Aβ1-42, and p-Tau were assessed through real time polymerase chain reaction (qPCR), enzyme linked immunosorbent assay (ELISA). Computational evaluation showed strong binding to NF-κβ, c-JNK, acetylcholinestrase (AChE), butyrylcholinestrase (BuChE) and TNF-α, supporting its multi-target potential. LW demonstrated neuropharmacological efficacy through preservation of neuronal structure, suppression of Aβ pathology, enhancement of cognitive function, restoration of antioxidant defenses, downregulation of proinflamatory, amyloidogenic, and tauopathic markers. These findings featured its potential as a multi target therapeutic agent for the management of AD.