Tanshinone IIA attenuates renal fibrosis and inflammation via altering expression of TGF-β/Smad and NF-κB signaling pathway in 5/6 nephrectomized rats

Purpose: In traditional Chinese medicine, Tanshinone HA is used to treat chronic kidney disease (CKD). However, its biological activity and mechanism of action in renal fibrosis and inflammation are not fully identified. The current study was conducted to determine the effects of Tanshinone HA treatment on CKD by assessing potential modulation of the TGF-beta/Smad and NF--kappa B signaling pathway. Methods: CICD was produced in rats by 5/6 nephrectomy. They were then divided into the following groups: control (sham operation); CKD (5/6 nephrectomy); 5/6 nephrectomy + Tanshinone HA (10 mg/kg in average, once a day for 16 weeks). Serum and urine samples were obtained from animals in each group, and serum creatinine (Scr), blood urea nitrogen (BUN) levels and 24 h urinary protein excretion were measured. Tissue samples from the kidney were used for morphometric studies (Masson's trichrome). The expression of fibronectin protein and collagen types 1,111, IV, and TGF-beta, TNF-alpha, CXCL-1, MCP-1, RANTES mRNA were evaluated using immunohistochemistry and RT-PCR analysis; the TGF-beta/Smad and NF-kappa B signaling pathway was detected by immunohistochemistry and Western blot analysis. Results: The following effects were observed in CKD rats treated with Tanshinone IIA: (1) marked improvements in Scr, and 24 h urine protein excretion; (2) significant reductions in protein and mRNA levels of fibronectin, collagen III, and collagen IV and TNF-alpha, MCP-1, and CXCL-1; (3) significantly inhibited the TGF-beta/Smad and NF-kappa B signaling activation. Conclusions: These results suggest that Tanshinone HA suppresses renal fibrosis and inflammation via altering expression of TGF-beta/Smad and NF-kappa B pathway in the remnant kidney, thus supporting the potential of Tanshinone HA as a new therapeutic agent for slowing the progression of CKD. (C) 2015 Elsevier RV. All rights reserved.