Drug Design, Development and Therapy (Dec 2020)
Tanshinone IIA Ameliorates Streptozotocin-Induced Diabetic Nephropathy, Partly by Attenuating PERK Pathway-Induced Fibrosis
Abstract
Shujuan Xu,1,* Lianjun He,2,* Keke Ding,3 Lingling Zhang,4 Xinhui Xu,5 Sheng Wang,6 Xueyi Qian2 1Department of Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Precision Medicine Centre, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 3Department of Urology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 4School of Pharmacy, Southwest Medical University, Luzhou, People’s Republic of China; 5School of Pharmacy, Wannan Medical College, Wuhu, People’s Republic of China; 6Department of Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyi Qian Tel +86-18756907022Email [email protected]: Tanshinone IIA (Tan IIA), a compound extracted from Salvia miltiorrhiza, can improve type II diabetes, while the molecular mechanisms underlying Tan IIA-mediated protective effects in diabetic nephropathy are unclear. This study explored the protective actions of Tan IIA on renal tissues in streptozotocin (STZ)-induced diabetic nephropathy.Materials and Methods: Tan IIA (2, 4, 8 mg/kg/day) was daily administered to STZ-treated rats by intraperitoneal injection for 42 days. The morphologic pathology was evaluated by hematoxylin-eosin and Masson’s trichrome staining, and transmission electron microscopy. The protein expression levels in renal tissues were evaluated by Western blotting and immunohistochemistry; the mRNA expression level was determined by quantitative real-time PCR.Results: Tan IIA at 2 and 4 mg/kg attenuated the increase in the levels of uric acid and blood urea nitrogen and restored the reduction in the superoxide dismutase activity in the serum of the diabetic rats. Tan IIA at 2 and 4 mg/kg, but not 8 mg/kg, ameliorated the thickening of renal tubule in the diabetic rats; Tan IIA at 2 and 4 and 8 mg/kg attenuated the thickening of glomerular basement membrane and the collagen deposition in the renal tissues of the diabetic rats. Tan IIA treatment at 2, 4, 8 mg/kg decreased the expression levels of transforming growth factor-beta1, TSP-1, Grp78 and CHOP in the diabetic rats. Tan IIA at 2 and 4 and 8 mg/kg attenuated the increase in the protein levels of p-PERK, p-elf2α and ATF-4 from the renal tissues of diabetic rats, while the protein level of AFT-6 and the mRNA expression levels of XBP-1t, XBP-1s and p58IPK in the renal tissues were not affected by STZ or Tan IIA treatment.Conclusion: Tan IIA-mediated protective effects on the STZ-induced diabetic nephropathy may be associated with the reduced endoplasmic reticulum stress via attenuating PERK signaling activities.Keywords: diabetic nephropathy, streptozotocin, tanshinone IIA, renal tissues, endoplasmic reticulum stress, PERK signaling
