Background: Diabetic nephropathy (DN) is a major cause of chronic kidney disease around the world. Endoplasmic reticulum (ER) stress plays an important role in DN progression. Ligustrazine (Lig) is derived from the Chinese herb Ligusticum wallichii and is reported to exert anti-oxidant, anti-inflammation and anti-fibrosis effects. The aim of our study was to investigate the influence of Lig on the treatment of DN. Methods: Streptozotocin (STZ) was used to induce diabetes in Sprague–Dawley (SD) rats. Then, STZ-induced rats were treated with different concentrations of Lig (50 or 150 mg kg−1 day−1) for 8 weeks of treatment. Urinary albumin concentrations, blood urea nitrogen (BUN), serum creatinine (Scr) and creatinine clearance (Ccr) were determined. The levels of proinflammatory cytokines (IL-8, IL-6, IL-1β and TNF-α) were estimated by ELISA. TUNEL assay was used for apoptosis index measurement. Western blot was used for the detection of GRP78, CHOP, p-eIF2α, eIF2α, p-p38, p-38, p-ERK1/2 and ERK1/2. Results: Lig treatment significantly reduced urinary albumin excretion, BUN and Scr and increased Ccr in STZ-induced rats. Lig also suppressed the levels of IL-8, IL-6, IL-1β and TNF-α and inhibited apoptosis dose-dependently. In addition, Lig inhibited GRP78 and CHOP expression and prevented the phosphorylation of eIF2α, p-38 and ERK1/2. Conclusion: Our study indicated that Lig attenuated renal damage by inhibiting ER stress in DN by inactivating MAPK pathways.
