Erythrina caffra Extract Restores Memory, Modulates Cholinergic Dysfunction, Neuroinflammation, and Attenuates Oxidative Stress in Cadmium-Induced Alzheimer's Disease-Like Pathology in Rats

Cadmium (Cd) is well known for its neurotoxic effects. Numerous studies have highlighted the link between its exposure and Alzheimer’s disease (AD), considering that AD is a multifactorial disorder influenced by a complex interplay of various factors, including environmental factors. Erythrina species, including Erythrina caffra , are a rich source of bioactive substances with anti-inflammatory, antioxidant, and anticholinesterase activities. However, current studies on the preventive potential of Erythrina caffra against heavy metals linked to neurodegeneration are insufficient. This study explored the impact of cadmium on the cholinergic system, oxidative stress, neuroinflammation, and memory as key pathological features implicated in AD and the therapeutic potential of Erythrina caffra seeds ethanolic extract in attenuating cadmium-induced AD-like alterations in Wistar rats. Rats were exposed to cadmium chloride directly through intracerebroventricular injections. The treated groups received 2.5 mg/kg of Erythrina caffra extract and 20mg/kg of memantine via gavage. Memory performance, cholinergic dysfunction, oxidative stress, neuroinflammation, and neuronal integrity were assessed upon completion of the experiment. Results showed significant alterations in cholinergic function, evidenced by decreased levels of acetylcholine, decline in antioxidant enzyme activities, catalase, and superoxide dismutase, in addition to a significant decrease in Non-protein thiols level, an increase in the levels of IL-6 and TNF-α, and neuronal loss in the hippocampus. Both treatments restored memory, modulated cholinergic dysfunction and neuroinflammation, and prevented neuronal integrity and mitigated oxidative stress caused by cadmium. These findings suggest that Erythrina caffra may represent a promising therapeutic potential in mitigating key pathological features of AD.