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Astaxanthin-loaded alginate-chitosan gel beads activate Nrf2 and pro-apoptotic signalling pathways against oxidative
Hamieh Goshtasbi1,2, Elaheh Dalir Abdolahinia2,3, Marziyeh Fathi2
1Department of Plant, Cell and Molecular Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Abstract:
Oxidative stress (OS) plays a crucial role in disease development. Astaxanthin (ATX), a valuable natural compound, may reduce OS and serve as a treatment for diseases like neurodegenerative disorders and cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and OS management. We evaluated ATX's antioxidant activity via Alg-CS/ATX gel beads in vitro. ATX-encapsulated alginate-chitosan (Alg-CS/ATX) gel beads were synthesized and structurally/morphologically characterized by SEM, FT-IR, and XRD. Their biological effects were examined in human umbilical vein endothelial cells (HUVECs) treated with H2O2 through MTT assay, Annexin V/PI, cell cycle studies, and western blotting. Alg-CS effectively carried ATX, with high capacity and reduced pore size. Alg-CS/ATX displayed an 84% encapsulation efficiency, maintaining stability for 30 days. In vitro studies showed a 1.4-fold faster release at pH 5.4 than at neutral pH, improving ATX's therapeutic potential. HUVECs treated with Alg-CS/ATX showed enhanced viability via increased Nrf2 expression. Alg-CS gel beads exhibit significant potential as a biocompatible vehicle for delivering ATX to combat OS with considerable opportunity for clinical applications.
Insights
Astaxanthin (ATX) delivered via alginate-chitosan gel beads effectively combats oxidative stress. This novel delivery system enhances cell viability by increasing nuclear factor-erythroid 2-related factor 2 (Nrf2) expression, showing promise for disease treatment.
Area of Science:
- Biomaterials Science
- Cell Biology
- Pharmacology
Background:
- Oxidative stress (OS) is implicated in various diseases, including neurodegenerative disorders and cancer.
- Astaxanthin (ATX), a natural antioxidant, shows therapeutic potential for OS-related conditions.
- Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key regulator of antioxidant responses.
Purpose of the Study:
- To evaluate the antioxidant efficacy of ATX delivered via alginate-chitosan (Alg-CS/ATX) gel beads.
- To characterize the physical and chemical properties of the Alg-CS/ATX gel beads.
- To assess the biological effects of Alg-CS/ATX on human umbilical vein endothelial cells (HUVECs) under oxidative stress.
Main Methods:
- Synthesis and characterization of Alg-CS/ATX gel beads using SEM, FT-IR, and XRD.
- In vitro release studies at different pH levels.
- Assessment of cell viability (MTT assay), apoptosis (Annexin V/PI), cell cycle, and Nrf2 expression (Western blotting) in H2O2-treated HUVECs.
Main Results:
- Alg-CS/ATX gel beads demonstrated high encapsulation efficiency (84%) and stability for 30 days.
- Faster ATX release was observed at acidic pH (5.4) compared to neutral pH.
- Treatment with Alg-CS/ATX significantly enhanced HUVEC viability and increased Nrf2 expression.
Conclusions:
- Alg-CS gel beads serve as an effective and biocompatible vehicle for ATX delivery.
- This delivery system shows potential for combating oxidative stress and offers opportunities for clinical applications.
- Enhanced Nrf2 expression highlights the mechanism by which ATX-loaded gel beads protect cells.
