Abstract

Dendrobium mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-β1 (TGF-β1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-β1 and alpha-smooth muscle actin (α-SMA), respectively, in renal tissues. TGF-β1, Smad2, p-Smad2, Smad3, p-Smad3, and α-SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-β1 and α-SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-β1/Smads signaling pathway.

Highlights

  • Diabetic nephropathy (DN) is a common chronic microvascular complication of diabetes and the most important cause of death in patients with diabetes [1, 2]

  • Mice in the normal group were in a good mental state, responsive, with shiny hair, and in a good feeding condition. db/db mice were listless and unresponsive, with increased diet and urine volumes; the above symptoms of mice in each treatment group were improved to different degrees compared with the model group

  • After the 4th week, there was a significant reduction in the fasting blood glucose (FBG) level in the Dendrobium mixture (DMix) group compared with the model group, and no statistically significant difference was observed between the DMix and positive control groups (P > 0.05), indicating that DMix could reduce blood glucose in db/db mice

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Summary

Introduction

Diabetic nephropathy (DN) is a common chronic microvascular complication of diabetes and the most important cause of death in patients with diabetes [1, 2]. Activation of the TGF-β1/Smads signal transduction pathway is an important mechanism for the development of renal fibrosis [5,6,7]. Dendrobium mixture (DMix) is a preparation used at the Second Affiliated Hospital of Fujian Traditional Chinese Medical University (batch number: Min Q/YZ2012-315; patent number: ZL201110408411.0) that was developed by Professor Shi Hong for the long-term clinical treatment of diabetes and its complications. It is composed of Dendrobium, Astragalus, Salvia miltiorrhiza, Rhizoma anemarrhenae, and other herbs. The effect of DMix on the TGF-β1/Smads signaling pathway in the renal tissue of db/db mice with DN was observed, and the mechanism by which it improves DN was discussed to Evidence-Based Complementary and Alternative Medicine provide an experimental basis for the use of DMix in clinical kidneys were removed, washed with normal saline, and practice

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