Trigonelline protects hippocampus against intracerebral Aβ(1-40) as a model of Alzheimer's disease in the rat: insights into underlying mechanisms

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common phenotype of dementia. Trigonelline is an alkaloid found in medicinal plants such as fenugreek seeds and coffee beans with neuroprotective potential and according to existing evidences, a favorable agent for treatment of neurodegenerative disorders. In this study, the possible protective effect of trigonelline against intracerebral Aβ(1-40) as a model of AD in the rat was investigated. For induction of AD, aggregated A(1-40) (10 μg/2 휇l for each side) was bilaterally microinjected into the hippocampal CA1 area. Trigonelline was administered p.o. at a dose of 100 mg/kg. The results showed that trigonelline pretreatment of Aβ-microinjected rats significantly improves spatial recognition memory in Y maze and performance in novel object recognition (NOR) task, mitigates hippocampal malondialdehyde (MDA), protein carbonyl, lactate dehydrogenase (LDH), and improves mitochondrial membrane potential (MMP), glutathione (GSH), and superoxide dismutase (SOD) with no significant change of catalase activity, nitrite level, caspase 3 activity, and DNA fragmentation. Additionally, trigonelline ameliorated hippocampal levels of glial fibrillary acidic protein (GFAP), S100b, cyclooxygenase 2 (Cox2), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) with no significant alteration of inducible nitric oxide synthase (iNOS). In addition, trigonelline pretreatment prevented loss of hippocampal CA1 neurons in Aβ-microinjected group. Therefore, our results suggest that trigonelline pretreatment in Aβ model of AD could improve cognition and is capable to alleviate neuronal loss through suppressing oxidative stress, astrocyte activity, and inflammation and also through preservation of mitochondrial integrity.

Keywords: Alzheimer’s disease; Amyloid beta; Hippocampus; Inflammation; Oxidative stress; Trigonelline.