Effects of total flavonoids from Oxytropis falcata Bunge on the SOCS/JAK/STAT inflammatory signaling pathway in the kidneys of diabetic nephropathy model mice

Abstract

To investigate the effects of total flavonoids from Oxytropis falcata Bunge on the inflammatory signaling pathway suppressor of cytokine signaling (SOCS)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) in diabetic nephropathy KK-Ay mice. KK-Ay mice were used to establish a diabetic nephropathy model. The general condition of the mice treated with different concentrations of total flavonoids from O. falcata was monitored, respectively. Body weight, blood glucose, 24-h urinary albumin (UAlb), serum creatinine (Cre), blood urea nitrogen (BUN), and uric acid (UA) levels were measured at different time points. Hematoxylin and eosin staining quantitative reverse transcription-polymerase chain reaction and western blotting were used to detect changes in renal tissues and glomerular mesangial cells. Four weeks after model establishment, body weight, blood glucose, and 24 h UAlb significantly increased in KK-Ay mice compared with that in control C57BL/6j mice ( P < 0.05). Compared with non-treated model mice, mice treated with total flavonoids from O. falcata for 4 weeks had significantly decreased serum Cre, BUN, and UA; monocyte chemoattractant protein-1(MCP-1), nuclear factor(NF)-κB, interleukin(IL)-6, and transforming growth factor(TGF)-β1, JAK 1, STAT 3 and STAT 4 mRNA levels; and p-JAK2 and p-STAT1 protein levels and significantly increased SOCS-1 and SOCS-3 protein levels in the kidneys. The treatment effects were dose-dependent and same to in vitro. Our results reflected that total flavonoids from O. falcata relieved renal tissue inflammation in diabetic mice by reducing blood glucose levels and inhibiting JAK/STAT signaling, thereby protecting against the development of diabetic nephropathy.