Neuroprotective Effect of Syringic Acid by Modulation of Oxidative Stress and Mitochondrial Mass in Diabetic Rats

Abstract

Diabetes is a metabolic complaint associated with oxidative stress and dysfunction of mitochondria. One of the most common complications of diabetes mellitus is neuropathy. This study evaluated the possible neuroprotective effects of syringic acid (SYR), a natural polyphenolic derivative of benzoic acid, on oxidative damage and mitochondria in the brain, spinal cord, and sciatic nerve of streptozotocin-induced diabetic rats. Different groups of rats including normal control, diabetics (induced by streptozotocin), diabetic groups treated with 25, 50, and 100 mg/kg of SYR, and non-diabetic group treated with only 100 mg/kg of SYR were treated for 6 weeks. Learning and memory function, physical coordination, and acetylcholinesterase (AChE) and antioxidant indexes, as well as mRNA expression of mitochondrial biogenesis, were measured in the brain, spinal cord, and sciatic nerves. Diabetic rats treated with 100 mg/kg SYR exhibited significantly improved learning, memory, and movement deficiency ($p<0.05$). SYR 100 mg/kg also significantly upregulated the brain mRNA expression of PGC-1α and NRF-1, the key regulators of energy metabolism, oxidative phosphorylation, and mitochondrial biogenesis. In addition, SYR 100 mg/kg and SYR 50 mg/kg increased the mtDNA/nDNA ratio in the brain and the spinal cord of diabetic rats, respectively ($p<0.05$). SYR attenuated the lipid peroxidation in all the tissues, but not significant effects were observed on GSH, AChE, catalase, and superoxide dismutase activity. In all the tests, nonsignificant differences were observed between the control and SYR 100 mg/kg groups. Moreover, SYR reduced inflammation and demyelination in sciatic nerves. This is the first study to reveal the regulation of mitochondrial biogenesis and energy metabolism by SYR, beyond its antioxidant role in the diabetic rats’ brain and spinal tissues.