Biological and Pharmacological Characterization of Ascorbic Acid and Nicotinamide Chitosan Nanoparticles against Insulin-Resistance-Induced Cognitive Defects: A Comparative Study

Abstract

High consumption of industrialized food with high fat content is generally associated with insulin resistance, which in turn causes memory impairment and cognitive decline. Nicotinamide and ascorbic acid are among the promising neuroprotective molecules; however, an appreciable therapeutic activity necessitates the administration of a large dose of either. Therefore, the study aimed to assess if loading them in chitosan nanoparticles in doses 5–10 times lower than the unencapsulated forms would achieve comparable therapeutic results. Animals were fed a high-fat-high-fructose (HFHF) diet for 75 days. The vitamins in their conventional form (100 mg/kg) and the nanoparticles under investigation (10 and 20 mg/kg) were given orally concomitantly with the diet in the last 15 days. The intake of HFHF diet for 75 days led to an insulin-resistant state, with memory impairment, which was verified behaviorally through the object recognition test. This was accompanied by significant reduction in brain insulin-like growth factor 1 (IGF-1), increased acetylcholine esterase activity, increase in the serotonin and dopamine turnover ratio, and increase in oxidative stress and 8-OHdG, indicating cellular DNA fragmentation. Cellular energy was also decreased, and immunohistochemical examination verified the high immunoreactivity in both the cortex and hippocampus of the brain. The administration of nanoparticulated nicotinamide or ascorbic acid with a 10 times lesser dose than the unencapsulated forms managed to reverse all aforementioned harmful effects, with an even lesser immunoreactivity score than the unencapsulated form. Therefore, it can be concluded that nicotinamide or ascorbic acid chitosan nanoparticles can be recommended as daily supplements for neuroprotection in patients suffering from insulin resistance after conduction of clinical investigations.

Intranasal ondansetron microemulsion counteracting the adverse effects of cisplatin: animal study

“…In addition, it was previously reported that 8-hydroxy-2-deoxyguanosine (8OHdG); which is a repair product of oxidized guanine lesions, is directly connected to elevated oxidative stress or disease states, and could be used as a reliable marker of cellular DNA damage and repair [ 50 – 53 ].…”

Curcumin nanoemulsion counteracts hepatic and cardiac complications associated with high‐fat/high‐fructose diet in rats

“…The first group of rats ( n = 10) were fed a standard control diet and tap water, serving as the normal control group. The other groups were administered HFHF diet for seventy‐five days (Abd‐Allah et al, 2020b, 2021) On the 60th day, insulin resistance (IR) was confirmed by measuring fasting glucose and insulin, and computing the fasting insulin sensitivity indices. Afterwards, treatments were supplemented orally for two weeks.…”

Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors

“…Other mechanisms are also compromised in WD-induced cognitive damage: insulin (INS) signaling in the brain [ 60 , 68 ], blood-brain barrier (BBB) permeability [ 41 , 57 , 62 ], HPC inflammation [ 45 , 46 , 49 , 54 , 60 , 68 ], microglia activation [ 54 , 57 , 65 , 68 , 72 ], endoplasmic reticulum (ER) and oxidative stress [ 43 , 51 , 58 , 60 , 61 , 71 ], gut microbiome composition [ 44 , 46 , 54 , 56 , 58 ], and neurogenesis [ 59 ]. Therapeutic strategies based on modulating these mechanisms have demonstrated unequal effects on memory loss.…”