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.

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.

This study shows the inhibitory effect of sea buckthorn (Hippophae rhamnoides L.) extracts, sea buckthorn leaf (HRL) and berry (HRB), on the formation of advanced glycation endproducts (AGEs), closely linked to diverse disease. In vitro assay revealed the superior inhibitory effect of HRL on the AGEs formation and AGEs-induced collagen crosslinking compared with that of HRB. Ultra-performance liquid chromatography-mass spectrometry results revealed that HRL displays a higher inhibition efficiency on the AGEs formation at 30 AGEs binding sites in bovine serum albumin than HRB. The high concentration of 3-sophoroside-7-rhamnoside in HRL compared with that in HRB may result in the strong inhibitory effect of HRL compared with that of HRB. HRL also exhibited significantly higher ABTS and DPPH radical scavenging activities than HRB. Overall, this study demonstrated that HRL has excellent potential as a dietary agent for controlling various diseases mediated by AGEs and oxidative stress.

Advanced glycation end-products (AGEs) such as methylglyoxal (MGO) play a vital role in the pathogenesis of nephropathy, a diabetic complication. In the present study, we evaluated the anti-glycation and renal protective properties of Ishige okamurae extract (IOE) against AGE-induced oxidative stress. HPLC analysis confirmed that bioactive phlorotannins such as diphlorethohydroxycarmalol and ishophloroglucin A are predominantly present in IOE. IOE showed strong anti-glycation activities via inhibition of AGE formation, inhibition of AGE–protein cross-linking, and breaking of AGE–protein cross-links. In addition, in vitro studies using mesangial cells demonstrated that IOE effectively suppressed intracellular reactive oxygen species production, intracellular MGO accumulation, and apoptotic cell death by MGO-induced oxidative stress, in addition to regulating the expression of proteins involved in the receptor for AGEs and nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathways. Therefore, IOE can serve as a natural therapeutic agent for the management of AGE-related nephropathy.