Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is the most chronic metabolic ailment characterized by insulin deficiency leading to aberrant cognitive dysfunction in later stages. Hesperidin is a bioflavonoid, having different pharmacological activities, but its poor water solubility and short plasma half-life restrict its applications in the clinical field. So, the hesperidin was conjugated with gold, selenium, and core-shell bimetallic nanoparticles of gold and selenium. Different spectroscopic methods characterized the synthesized monometallic and bimetallic nanoparticles. The rats were injected with streptozotocin to induce cognitive dysfunction, followed by administering HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs daily for 21 days. Then, the neurobehavioral studies, oxidative stress parameters, AChE and nitrite levels, the content of amyloid-β42, and inflammatory mediators were accessed to evaluate the effect of the nanoparticles against the STZ rat model. The results showed a significant increase in oxidative stress, AChE activity, amyloid-β42, nitrite levels, and neuroinflammation by upregulating the inflammatory cytokines in the streptozotocin-administered rat brain. The HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs effectively reversed all these effects of streptozotocin. However, the bimetallic nanoparticle Se@Au-HSP NPs revealed better neuroprotective action than HSP-Au NPs and HSP-Se NPs. Hesperidin-conjugated bimetallic nanoparticles improved learning and memory in the STZ rat model and may be an alternative approach for neurodegenerative diseases, including Alzheimer's disease.