Abstract
Eucommia ulmoides Oliv. (EU), also known as Du-Zhong, is a medicinal herb commonly used in Asia to treat hypertension and diabetes. Despite evidence of the protective effects of EU against diabetes, its precise effects and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of EU on AGEs-induced renal disease and explored the possible underlying mechanisms using streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice received EU extract (200 mg/kg) orally for 6 weeks. EU treatment did not change blood glucose and glycated hemoglobin (HbA1c) levels in diabetic mice. However, the EU-treated group showed a significant increase in the protein expression and activity of glyoxalase 1 (Glo1), which detoxifies the AGE precursor, methylglyoxal (MGO). EU significantly upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression but downregulated that of receptor for AGE (RAGE). Furthermore, histological and immunohistochemical analyses of kidney tissue showed that EU reduced periodic acid–Schiff (PAS)-positive staining, AGEs, and MGO accumulation in diabetic mice. Based on these findings, we concluded that EU ameliorated the renal damage in diabetic mice by inhibiting AGEs formation and RAGE expression and reducing oxidative stress, through the Glo1 and Nrf2 pathways.
Highlights
Diabetes mellitus is one of the most complicated diseases, and its etiology is not yet thoroughly understood
We investigated the inhibitory effects of treatment significantly increased cross-links to collagen
MGO staining in the diabetic kidney glomeruli; Eucommia ulmoides Oliv. (EU) treatment reduced the deposition of MGO (Figure 5). These results suggest that EU treatment inhibited advanced glycation end-products (AGEs) formation by increasing glyoxalase 1 (Glo1) expression and activity
Summary
Diabetes mellitus is one of the most complicated diseases, and its etiology is not yet thoroughly understood. Diabetes mellitus can cause secondary complications such as heart disease, stroke, retinopathy, nephropathy, and neuropathy. AGEs can be formed endogenously via a non-enzymatic glycation reaction between reducing sugars and the free amino groups of proteins or lipids [2]. This non-enzymatic reaction of proteins and lipids leads to the formation of AGEs by molecular rearrangements. AGEs induce oxidative stress, inflammatory reactions, and thrombosis by interacting with their receptors (RAGEs) [3]. They are involved in vascular aging, cataract generation, retinopathy, atherosclerosis, and nephropathy [1]. AGEs accumulate in the glomeruli where they increase the expression of type-IV collagen and laminin in the extracellular matrices [4] and induce irreversible cross-linked protein formation [5]
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