The biochemical integrity of the brain is essential for the functioning of the central nervous system (CNS). Oxidative stress is one of the parameters that contribute to brain biochemical disorders. The brain is highly susceptible to oxidative stress due to its high oxygen consumption and rich lipid content. As a result, oxidative stress can alter the normal function of the CNS. Therefore, oxidative stress can disrupt normal cell signaling mechanisms. The use of plant metabolites has been proven as one of the most potential therapeutic strategies to inhibit the effects of anxiety and reduce the level of oxidative stress. Two of these metabolites are syringic acid (SA) and quercetin (QU) which are known as natural flavonols with significant pharmacological effects. This study aims to investigate the synergistic antioxidant effect of the SA-Qu combination inhibitory/protective effect on memory deficit and oxidative stress induced by intraventricular injection of streptozotocin in rats. Rats were randomly divided into five groups (n=7): control group, streptozotocin-treated group, and streptozotocin treatment groups receiving syringic acid, quercetin and the combination of these compounds. After surgery, rats in all groups except the control and streptozotocin-treated group were gavaged with SA, QU and QU+SA(1:1) at a 50 mg/kg dose for 21 days. Then, memory performance, anxiety and stress were examined by cross-maze, shuttle box and new object recognition tests. Also, the activity of antioxidant enzymes catalase, superoxide dismutase, acetylcholinesterase enzyme, and glutathione and malondialdehyde levels were evaluated. Anxiety-like behaviors as well as impairment in learning and cognitive function have increased with streptozotocin injection. In addition, streptozotocin decreased the activities of antioxidant enzymes and acetylcholine, increasing the level of peroxidation. While the simultaneous treatment with syringic acid and quercetin with a synergistic effect has improved memory and learning performance and also reduced anxiety. In addition, it has caused an increase in the activity of antioxidant enzymes along with a decrease in the level of lipid peroxidation and a decrease in the activity of the acetylcholinesterase enzyme, and an increase in the level of acetylcholine in the brain. The results suggest that the synergistic effect of syringic acid and quercetin compounds may be related to anxiety-like behaviors and memory function induced by streptozotocin through reducing oxidative stress. Therefore, the use of quercetin and syringic acid is recommended for effective and low-risk treatment for anxiety conditions caused by oxidative stress and neurological diseases such as Alzheimer's.
