ABSTRACT Alzheimer's disease (AD) is a progressive neurodegenerative disorder, posing a global health challenge. It affects millions of people, causing cognitive decline and a heavy burden on healthcare systems. Neuroinflammation is a key pathological feature of AD, often associated with the dysregulation of microRNAs such as hsa‐miR‐146a‐5p. WGX50 (N‐2‐(3,4‐Dimethoxy‐phenyl)‐ethyl‐3‐phenyl‐acrylamide), a small molecule derived from Zanthoxylum bungeanum Maxim, has antioxidant and anti‐inflammatory activities. While WGX50 demonstrates potent inhibition of neuroinflammation, its poor blood–brain barrier permeability may be improved using targeted delivery strategies. The current study aimed to design a novel nanoconjugate of WGX50 and curcumin with gold nanoparticles (AuNPs) to observe its therapeutic effects in a rat model. All nanoconjugates were synthesised as targeted (Cys‐capped AuNPs with WGX50‐insulin and curcumin‐insulin) and non‐targeted (without insulin). Immunohistochemical analysis revealed that both non‐targeted (WGX50‐NT) and targeted (WGX50‐T) therapies have a significant effect in the rat model, with WGX50‐T showing a more pronounced effect. The histopathology results of WGX50 and WGX50‐T showed an approximate 80%–90% reduction in Aβ plaque deposition. The treatment with both curcumins targeted (C‐T) and non‐targeted (C‐NT) formulations led to a significant reduction in Aβ levels in AD rats. Fluorescence microscopy confirmed that targeted delivery was more effective, potentially leading to better therapeutic outcomes. The expression levels of hsa‐miR‐146a‐5p showed differential expression levels with targeted treatments correlating with lower expression levels, suggesting a role in modulating neuroinflammation and immune responses. Overall, these findings highlight the potential of targeted drug delivery systems in enhancing the efficacy of AD treatments.
Lodhi et al. (Sun,) studied this question.