Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease

Abstract

Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood–brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6‐RES‐OPC‐HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6‐RES‐OPC‐HA nanoparticles have the potential to prevent and alleviate early AD.

Lactic Acid Bacteria-Derived Exopolysaccharides Mitigate the Oxidative Response via the NRF2-KEAP1 Pathway in PC12 Cells

“…Zhang et al 61] showed that AD patients have significantly elevated levels of ROS in the brain, experiencing OS. The high intracellular ROS levels in the H 2 O 2 group found in our study are similar to those reported by Zhang et al [77] in patients with AD. However, while the study of Zhang et al [77] included patients with AD, our study included PC-12 cells induced by OS with H 2 O 2 (in vitro ND model).…”

“…The high intracellular ROS levels in the H 2 O 2 group found in our study are similar to those reported by Zhang et al [77] in patients with AD. However, while the study of Zhang et al [77] included patients with AD, our study included PC-12 cells induced by OS with H 2 O 2 (in vitro ND model). In research conducted by Zhang et al [78], the EPS from L. plantarum YW11 displayed a remarkable scavenging ability, with IC 50 values against hydroxyl radical of 75.10% and 1.22 mg/mL, and against superoxide anion radical of 62.71% and 1.54 mg/mL.…”

Role of Nanoparticle-Conjugates and Nanotheranostics in Abrogating Oxidative Stress and Ameliorating Neuroinflammation

“…Nonetheless, the clinical utility of these pharmacological agents is hampered by challenges such as limited absorption, chemical instability, and suboptimal efficacy, which impose constraints on their widespread momentum in the medicament of free radical-associated diseases [156]. Certain studies have demonstrated that conjugated or functionalized NPs can cross the blood-brain barrier (BBB) and exhibit their neuroprotective role against ROS-mediated neuronal toxicity and brain inflammation [160][161][162][163].…”