Syringic acid ameliorates experimental diabetic nephropathy in rats through its antiinflammatory, anti-oxidant and anti-fibrotic effects by suppressing Toll like receptor-4 pathway

Diabetic nephropathy (DN) is an important healthcare challenge because it occurs in about 40% of diabetic people and is a main cause end-stage renal disease. Toll like receptor-4 (TLR-4) signaling is involved in DN incidence and progression through its activation by hyperglycemia and hyperglycemia-induced alterations besides its crucial roles in initiating inflammation and fibrosis in kidney. Syringic acid is a natural phenolic acid. It is naturally available in many fruits and vegetables, including swiss chards, grapes and olives. In this study, Reno protective effects of syringic acid, as anti-inflammatory, anti-oxidant and anti-fibrotic natural compound, against experimental DN were investigated. Streptozotocin (45mg/kg) was used in inducing rat model of DN pathogenesis. In kidney homogenate, concentrations of TLR-4, interleukin-6 and transforming growth factor β1 (TGFβ1) were estimated by ELISA technique. Moreover, hydroxyproline and relevant collagen content in kidney tissues were evaluated using spectrophotometry. Oral administration of syringic acid (50 mg/kg) for 8 weeks succeeded in keeping kidney function evidenced by significant decrease in serum levels of creatinine, blood urea nitrogen (BUN) and decreased urinary protein content. Besides, it led to significant increase in renal superoxide dismutase (SOD) activity and significant decline in kidney malondialdehyde (MDA) content. Moreover, it showed significant anti-inflammatory and anti-fibrotic effects reflected by significant decrease in levels of TLR-4, interleukin-6, TGFβ1 and collagen in kidney homogenate as compared to DN group. Besides, it significantly attenuated DN-induced histopathological deteriorations. In conclusion, syringic acid can be proposed as an effective natural compound in halting DN progression through inhibiting TLR-4 pathway resulting in ameliorating oxidative stress, inflammation and fibrosis in kidney tissues.