Effect of Melilotus Extract and Exercise on Oxidative Stress and Neuroinflammation in an Alzheimer's Mouse Model

Abstract

Background: Oxidative stress and neuroinflammation are key factors in the pathophysiology of Alzheimer's disease (AD). Objectives: This study aimed to investigate the effects of resistance training on gene expression and certain neuroinflammatory and oxidative stress indicators in the hippocampus and testicular tissue of male rats with AD. Methods: Fifty-five eight-week-old male Wistar rats were obtained and randomly divided into four groups: Alzheimer's control, Alzheimer's + training, Alzheimer's + melilotus, and Alzheimer's + melilotus + training. An additional 11 rats were included in a healthy control group. Alzheimer's disease was induced in the rats. The intervention protocol included resistance training and melilotus administration. In the resistance training protocol, a weight was attached to the rats' tails, requiring them to lift these weights up 26 steps of a ladder. Complementary groups also received melilotus. Seventy-two hours after the last session, the rats were euthanized, and the hippocampus was extracted for further analysis. A two-way ANOVA test was used to estimate differences between groups after the induction of AD (P ≤ 0.05). Primers were designed, cDNA was prepared, and specific tissues were analyzed. Results: The results showed that exercise and melilotus consumption decreased the levels of the beta-secretase enzyme, testicular clusterin, nerve growth factor (NGF), and Brain-Derived neurotrophic factor (BDNF) genes, and increased nuclear erythroid-related factor 2 (Nrf2), peroxiredoxin 6 (PRDX6), and lysine acetyltransferase 2B (KAT2B), with significant differences observed between the groups. Conclusions: The intervention of exercise and melilotus extract consumption positively affected health and reduced the progression of AD. The independent variables' intervention modified the expression of genes related to AD, likely due to increased brain blood flow from exercise, synaptic strengthening of neurons, and the anti-inflammatory and antioxidant properties of melilotus.