Arctigenin ameliorates renal impairment and inhibits endoplasmic reticulum stress in diabetic db/db mice

Aims Diabetic nephropathy (DN) is the most common complication of diabetes mellitus. Endoplasmic reticulum (ER) plays an important role in the development and progression of DN. Arctigenin (ATG), a lignan extract from Fructus Arctii , exhibits anti-inflammatory, anticarcinogenic, anti-oxidative stress and immunomodulatory properties. The present research aimed to investigate whether ATG could protect against diabetes-related renal injury and inhibit ER stress in db / db mice. Main methods Male db / db mice were randomly divided into two groups: DN group and ATG treatment group (DN + ATG). db / m mice were defined as the normal control group (NC). ATG was dissolved in 0.5% carboxymethyl cellulose sodium salt solution and administered orally at a dose of 80 mg/kg to mice in the DN + ATG group once daily for 8 consecutive weeks. HK2 cells were used to determine the effects of ATG on ER stress and cell apoptosis in vitro . Key findings ATG administration significantly reduced blood glucose, urine albumin excretion, and urine albumin to creatinine ratio, and attenuated renal pathological injury when compared with untreated db / db mice. These changes were accompanied by decreased expression of both ER stress-related markers and caspase 12 level in the kidneys of db / db mice. In vitro , high glucose activated ER stress signal transduction pathway and induced cell apoptosis in HK2 cells, which were blocked by ATG. Significance Our results suggest that ATG exerts renoprotective effects on diabetes-related renal injury in db / db mice and cytoprotective effects on high glucose induced cell apoptosis and inhibits ER stress.