Arctigenin ameliorates renal impairment and inhibits endoplasmic reticulum stress in diabetic db/db mice.
Life Sci. 2019 Apr 15 ;223:194-201. Epub 2019 Mar 18. PMID: 30898648
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.