Spatholobus suberectus Ameliorates Diabetes-Induced Renal Damage by Suppressing Advanced Glycation End Products in db/db Mice.

Moon Do,Jiwon Choi,Sang Ha,Ho-Young Park,Jinyoung Hur,Yoonsook Kim

doi:10.3390/ijms19092774

Moon Do, Jiwon Choi + Show 4 more

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https://doi.org/10.3390/ijms19092774

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Abstract

Spatholobus suberectus (SS) is a medicinal herb commonly used in Asia to treat anemia, menoxenia and rheumatism. However, its effect of diabetes-induced renal damage and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of SS on diabetes-induced renal damage and explored the possible underlying mechanisms using db/db type 2 diabetes mice. db/db mice were administered SS extract (50 mg/kg) orally for 6 weeks. SS-treated group did not change body weight, blood glucose and glycated hemoglobin (HbA1c) levels. However, SS treatment reversed diabetes-induced dyslipidemia and urinary albumin/creatinine ratio in db/db mice. Moreover, SS administration showed significantly increased protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a transcription factor for antioxidant enzyme. SS significantly upregulated glyoxalase 1 (Glo1) and NADPH quinine oxidoreductase 1 (NQO1) expression but reduced CML accumulation and downregulated receptor for AGEs (RAGE). Furthermore, SS showed significant decrease of periodic acid–Schiff (PAS)-positive staining and AGEs accumulation in histological and immunohistochemical analyses of kidney tissues. Taken together, we concluded that SS ameliorated the renal damage by inhibiting diabetes-induced glucotoxicity, dyslipidemia and oxidative stress, through the Nrf2/antioxidant responsive element (ARE) stress-response system.

Highlights

Diabetes mellitus is one of the most complicated diseases; current knowledge about its cause remains limited
The findings indicate that the effects of the S. suberectus extract on the reduction of advanced glycation end products (AGEs) accumulation and receptor for AGEs (RAGE) expression was attributable to the upregulation of NADPH quinine oxidoreductase 1 (NQO1) and glyoxalase 1 (Glo1) proteins through nuclear factor erythroid 2-related factor 2 (Nrf2) overexpression
S. suberectus extract treatment resulted in an increased expression of NQO1, a multifunctional antioxidant enzyme, and Glo1. These results suggested that S. suberectus extract treatment reduced AGEs accumulation and AGEs-RAGE interaction by upregulating Glo1 and NQO1 expression via the Nrf2 pathway in the kidney, thereby ameliorating diabetic nephropathy

Summary

Introduction

Diabetes mellitus is one of the most complicated diseases; current knowledge about its cause remains limited. Diabetic nephropathy is one of the most common complications of diabetes and the leading cause of end-stage renal disease through several pathologic pathways [2]. It is well-known that renal cell loss in early diabetic nephropathy can be caused by hyperglycemia, oxidative stress, and formation of advanced glycation end products (AGEs) [3]. Some of ACCORD studies found glycemic control did not effective to prevent diabetic complications [7,8] For these reason, Moraru et al suggested that insulin resistance and hyperglycemia are result from the disease, but are not part of the causal cascade leading to type 2 diabetes [9]. Ameliorating of AGEs-induced glucotoxicity might be an important to treatment of diabetic complications

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