L -Theanine Ameliorates d -Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways

Abstract

The maintenance of homeostasis is essential for mitigating stress and delaying degenerative diseases such as Alzheimer's disease (AD). AD is generally defined as the abnormal production of β-amyloid (Aβ) and advanced glycation end products (AGEs). The effects of l-theanine on Aβ and AGE generation were investigated in this study. Decreased AGEs and Aβ1-42 levels were reflected by increased acetylcholine (ACh) concentration and acetylcholinesterase (AChE) activity inhibition compared to model rats. l-Theanine also inhibited nuclear factor-κB (p65) protein expression by activating sirtuin1 (SIRT1), reducing inflammatory factor expression, and downregulating the mRNA and protein expression of AGE receptors (RAGE). Superoxide dismutase 2 and catalase protein expressions were markedly upregulated by l-theanine, whereas oxidative stress-related injury was alleviated. The expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was also found to be increased. H&E staining showed that the apoptosis of hippocampal neurons was mitigated by decreased Bax and cleaved-caspase-3 protein expression and the increase of Bcl-2 protein expression. Moreover, l-theanine increased the gene and protein expression of brain-derived neurotrophic factor (BDNF). These findings suggest that the potential preventive effects of l-theanine against AD may be attributed to its regulation of SIRT1 and BDNF proteins and its mitigation of AGEs/RAGE signaling pathways in the brain tissue of AD model rats.