EUCOMMIA ULMOIDES OLIV. EXTRACT REGULATES AGE-INDUCED INJURY IN TUBULAR ENDOTHELIAL CELLS VIA THE RAGE-NRF2 PATHWAY
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The leaves, stems, and bark of Eucommia ulmoides Oliv. (EU), also known as Du-Zhong, have traditionally been used to cure various diseases, such as liver, kidney, and muscle diseases, in Asia. Despite evidence for protective effects against renal complications, its precise effects and mechanisms of action are unclear. In this study, the effects of EU on advanced glycation end products (AGEs)-induced renal disease and its mechanism were examined. NRK 52E normal rat kidney tubular epithelial cells were treated with AGEs and an EU extract. Expression levels of TGF-β1, an indicator of renal cell damage, and catalase, an antioxidant marker, were examined. Nuclear factor-E2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (keap1), and p65 regulation were examined to identify additional antioxidant mechanisms related to renal cell apoptosis and AGEs-induced renal cell damage. The effects of EU on mitogen-activated protein kinase (MAPK), Akt, and phosphoinositide 3-kinase (PI3K), which are involved in apoptosis, were also examined. TGF-β1 expression increased in response to AGEs and decreased by additional treatment with EU. Additionally, EU increased the expression of catalase. We found that EU increased Nrf2, keap1, and p65 and regulated the expression of RAGE (receptor for AGEs) and its downstream target Sirt1. EU also regulated the AGEs-altered phosphorylation of apoptosis factors. Based on these findings, we concluded that EU regulates AGEs-induced renal cell damage via antioxidant and apoptosis-related mechanisms.
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