Chitosan–Ellagic Acid Nanohybrid for Mitigating Rotenone-induced Oxidative Stress

Abstract

Antioxidants derived from nature, such as ellagic acid (EA), demonstrated high potency to mitigate neuronal oxidative stress and related pathologies, including Parkinson’s disease. However, the application of EA is limited due to its toxicity at moderate doses and poor solubility, cellular permeability, and bioavailability. Here, we introduce a sustainably resourced, green nanoencasement strategy to overcome the limitations of EA and derive synergistic effects to prevent oxidative stress in neuronal cells. Chitosan, with its high biocompatibility, potential antioxidant properties, and flexible surface chemistry, was chosen as the primary component of the nanoencasement in which EA is immobilized. Using a rotenone model to mimic intracellular oxidative stress, we examined the effectiveness of EA and chitosan to limit cell death. Our studies indicate a synergistic effect between EA and chitosan in mitigating rotenone-induced reactive oxygen species death. Our analysis suggests that chitosan encapsulation of EA reduces the inherent cytotoxicity of the polyphenol (a known anticancer molecule). Furthermore, its encapsulation permits its delivery via a rapid burst phase and a relatively slow phase making the nanohybrid suitable for drug release over extended time periods.

Ellagic Acid Prevents Dopamine Neuron Degeneration from Oxidative Stress and Neuroinflammation in MPTP Model of Parkinson’s Disease

“…However, EA treatment prior to MPTP administration significantly increased the GSH level and decreased the MDA level, again suggesting the antioxidant function of EA. In several studies, EA has been widely reported to exert free radical scavenging and potent antioxidant activity by scavenging ROS and restoring the activity of cellular antioxidant enzymes [31][32][33][34][35].…”

Electrosprayed chitosan‐coated alginate–pectin beads as potential system for colon‐targeted delivery of ellagic acid

“…The peak intensity at 1026 cm −1 seen in pure powders was reduced with bead formation due to perturbation by calcium and weakening in the bonds 36 . The chitosan spectrum used in this study showed an absorption peak marked at 1620 and 1518 cm −1 (LC) and 1648 and 1590 cm −1 (HC) attributed to the carbonyl stretching of amide (amide I band) and bending vibrations of NH (amide II) and at 1456 cm −1 corresponding to amide III vibrations 38,39 . The characteristic peaks of chitosan that appeared at 1590 cm −1 were overlapping with alginate; the peak of amino groups (NH 2 ) of chitosan at 1150 cm −1 showed itself as a shouldering peak in the chitosan‐coated beads with lower intensity due to a partial covalent bonding between calcium and oxygen atoms present in the chitosan structure 40 …”

Natural Phytochemicals as Novel Therapeutic Strategies to Prevent and Treat Parkinson’s Disease: Current Knowledge and Future Perspectives

“…Furthermore, the nanoformulation outperformed free EA in several activities: amelioration of apoptosis, inhibition of Cyto-C release, activation of caspases, regulation of P53, Bax, and Bcl-2 protein expression, and protection against DNA damage. Moreover, the EA and chitosan-coated combination mitigated rotenone-induced ROS overproduction and reduced cytotoxicity [355]. The antioxidant and antiaging properties of CA-loaded nanotransfersomes were found to enhance cell viability, reduce intracellular ROS generation, attenuate lipid peroxidation, and modulate MMP expression [350].…”