Author: Raisa Mahboob
Mahboob, Raisa, 2025 Neuroprotective activities of industry-grade fucoxanthin and fucoidan alone and in combination against beta-amyloid and hydrogen peroxide-induced neurotoxicity in PC12 cell line, Flinders University, College of Medicine and Public Health
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Introduction: Alzheimer’s disease (AD) is a chronic neurodegenerative disorder marked by gradual loss of memory and cognitive decline. It is characterised pathologically by the accumulation of beta-amyloid (Aβ1-42) plaques, oxidative stress, and mitochondrial dysfunction in brain cells. The available treatment options only relieve symptoms but do not prevent disease progression. Thus, marine-derived natural products, such as fucoxanthin and fucoidan, are gaining popularity due to their antioxidant, anti-inflammatory, and neuroprotective effects. However, most previous research has been conducted with highly pure analytical-grade compounds, which are not only expensive but also impractical for large-scale use. We hypothesised that these compounds would show neuroprotection against beta-amyloid and hydrogen peroxide-induced stresses in PC12 cells, and their combination would show synergistic effects. Methods: PC12 cells were treated with different concentrations of industrial-grade FX1, FX4 and FD. The cells were then exposed to amyloid-beta (1 µM and 2 µM) and hydrogen peroxide (100 µM and 150 µM), which induced cytotoxicity. The MTT assay measured cell viability. The Chou-Talalay method was used to determine the combined neuroprotective potential of the compounds. The CI value obtained helped to determine the effects are synergistic (CI <1), additive (CI=1) or antagonistic (CI ˃1). Results: FX1, FX4 and FD significantly provided dose-dependent neuroprotective effects when tested individually against both Aβ and H2O2 induced cytotoxicity. FX4 (20 µg/mL), which is lower in purity (5.6%), showed protection similar to FX1 (95.6%) at 10 µg/mL. FD in all concentrations showed protection against both stresses. Combination treatments restored up to 93% viability for FX1+FD at 5+25 µg/mL, 10+25 µg/mL and FX4+FD at 20+25 µg/mL, respectively, with CI < 1 showing a synergistic effect. The combinations restored cell viability at higher concentrations of the stress (2 µM of Aβ and 150 µM of H2O2). Although under high stress, fewer concentrations were found to be synergistic, which may be due to any previous cellular damage. Conclusion: This study demonstrated that industry-grade fucoxanthin and fucoidan exhibited neuroprotective effects against beta-amyloid and hydrogen peroxide-induced cytotoxicity in PC12 cells. They have demonstrated neuroprotection when used individually against the induced stress. However, in combination, the protection was better than the sum of their individual effects. This result supported our hypothesis that, in combination, they will show a synergistic effect. Moreover, FX4, being of low purity, was found to be as potent as higher-purity FX1. This might be due to the presence of other crude extracts that are contributing to neuroprotection. These findings align with the earlier research on pure compounds. Therefore, these results demonstrate the potential of industrial-grade purity of fucoxanthin and fucoidan as an affordable neuroprotective agent for early-stage prevention of Alzheimer’s disease.
Keywords: Alzheimer’s disease, industrial-grade fucoxanthin, industrial-grade fucoidan, Aβ1–42-induced cytotoxicity, H₂O₂-induced oxidative stress, PC12 cells, synergistic neuroprotection
Subject: Biotechnology thesis
Thesis type: Masters
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Prof. Wei Zhang