Neuroprotective Effect of Fucoxanthin against Intracerebroventricular Streptozotocin (ICV-STZ) Induced Cognitive Impairment in Experimental Rats

Background: Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neurotransmitter levels, and excessive deposition of Aβ(1-42) plaques. Fucoxanthin is a carotenoid with potential antioxidant, anti-inflammatory, and neuroprotective actions. Objective: In the present study, fucoxanthin was employed as a protective strategy in Intracerebroventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment. Methods: STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (ACh, GABA Glutamate), Aβ(1-42) and Tau protein measurements. Results: STZ-infused rats showed significant impairment in learning and memory, increased oxidative stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cytokine release, and change in neurotransmitters level. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and restored neurotransmitters concentration. Conclusion: The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ(1-42) accumulation, and tau protein.