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Prunella vulgaris attenuates diabetic renal injury by suppressing high glucose‐induced mesangial fibrosis and inflammation

Prunella vulgaris, well‐known traditional medicinal plant, is used for the cure of abscess, scrofula, hypertension and urinary diseases. The present study was designed to investigate the beneficial effects of aqueous extract of Prunellae vulgaris (APV) on high glucose (HG)‐promoted human mesangial cell and STZ‐induced diabetic rats. Pretreatment of APV (1‐50 μg/ml) attenuated 25 mM HG‐induced inflammatory marker such as intracellular cell adhesion molecule‐1 (ICAM‐1) and monocyte chemoattractant protein‐1 (MCP‐1) in mesangial cells. Additionally, APV suppressed transforming growth factor α1 (TGF‐α1) and Smad‐2/4 expression, whereas increased Smad‐7 expression level. Activation of p38 has been implicated in TGF‐α1‐stimulated collagen mRNA expression, whereas ERK has been associated with fibronectin accumulation. APV not only inhibits the Smad pathway, but also elicits inhibitory effects on ERK signaling. Connective tissue growth factor (CTGF) and collagen IV, fibrosis biomarkers, were significantly decreased by APV. Moreover, APV inhibited activation and translocation of nuclear factor kappa B (NF‐κB) in HG‐stimulated mesangial cells. Sprague‐Dawley rats were divided into five groups: control, STZ, STZ were fed on APV (100 or 300 mg/kg/day) and STZ with aminoguanidine (AG) (100 mg/kg/day) for 8 weeks respectively. The renal tissue in the APV group exhibited clear signs of inflammation compared with the control group. Additionally, APV increased nephrin expression in STZ‐induced diabetic kidney. Glomerulus TGF‐α1 expression in immunohistochemical staining was significantly decreased by APV. These findings suggest that APV have protective effect against diabetic nephropathy including inflammation and fibrosis through disturbing TGF‐α/Smad signaling.