Betacyanins attenuates diabetic nephropathy in mice by inhibiting fibrosis and oxidative stress via the improvement of Nrf2 signaling

Abstract

Diabetic nephropathy (DN) is a major cause of mortality in patients with diabetes, but there is a lack of effective therapeutic drugs for the disease treatment. Betacyanins (BCN) derived from plants exhibits anti-oxidative, anti-tumor and anti-inflammatory activities. However, its effects on DN have not been reported. In this study, we found that BCN supplementation markedly alleviated metabolic disorder and renal dysfunction in db/db mice. Additionally, BCN treatment obviously mitigated podocyte damage in diabetic mice, as evidenced by the decreased glomerular basement membrane thickness and the foot process width. Pathological analysis demonstrated that renal fibrosis was significantly inhibited by BCN through suppressing transforming growth factor (TGF)-β1/SMADs signaling in diabetic mice. Furthermore, diabetes-induced oxidative stress in kidney samples was evidently reduced in mice supplemented with BCN by improving nuclear factor erythroid-derived 2-related factor 2 (Nrf2) nuclear expression. The anti-fibrotic and anti-oxidant activities of BCN were confirmed in high glucose (HG)-stimulated podocytes in vitro. Importantly, we found that Nrf2 suppression could further exacerbate HG-induced collagen accumulation and reactive oxygen species (ROS) production in podocytes. Meanwhile, BCN-ameliorated fibrosis and oxidative stress were almost abrogated by the Nrf2 knockdown in HG-incubated podocytes. These findings elucidated that BCN could alleviate DN through reducing collagen and ROS deposition mainly through improving the Nrf2 signaling, subsequently alleviating renal dysfunction. Thus, BCN could be considered as a promising therapeutic agent for DN treatment.

Keywords

• Diabetic nephropathy
• Betacyanins (BCN)
• Fibrosis
• Oxidative stress
• Nrf2