Nanogel Delivery of Plumbagin from Nepenthes Khasiana Attenuates Neuroinflammation and Cognitive Decline in Alzheimer's Mice Models.

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by memory deficits, oxidative stress, and neuroinflammation. Plumbagin (PB), a bioactive naphthoquinone derived from Nepenthes khasiana, possesses therapeutic potential but is limited by poor solubility and bioavailability. To overcome these challenges, PB was encapsulated into hyaluronic acid nanogels (PB-NGs) and systematically evaluated for anti-Alzheimer's efficacy. The study aimed to evaluate the neuroprotective and anti-inflammatory properties of PB-NGs by in vitro and in vivo analyses. PB-NGs were synthesized and characterized using FT-IR, NMR, and TEM, confirming successful encapsulation. In silico docking demonstrated strong binding affinities of PB to β-amyloid and tau proteins, suggesting potential inhibition of AD-related pathological processes. In vitro, PB-NGs significantly decreased ROS production, mitigated pro-inflammatory cytokines (IL-1β, TNF-α), and improved cell viability in LPS-stimulated SH-SY5Y cells relative to free PB. In vivo, administration of PB-NGs to AD-induced mice significantly improved behavioral outcomes, including enhanced spatial memory and exploratory activity in Y-maze, open field, and Morris's water maze tests. Biochemical assays further revealed reduced oxidative stress (decreased MDA, increased SOD, CAT, GST) and modulation of cholinergic dysfunction (reduced AChE, increased ChAT). Histopathological analysis supported neuronal protection with diminished amyloid burden. Collectively, these findings demonstrate that PB-NGs effectively enhance bioavailability and exert significant neuroprotective and anti-inflammatory effects, supporting their potential as a promising nanotherapeutic approach for mitigating cognitive deficits in AD.