Department of General Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
J Food Drug Anal. 2019 Jul;27(3):736-748. doi: 10.1016/j.jfda.2018.12.009. Epub 2019 Jan 8.
Diabetic nephropathy is not only a common and severe microvascular complication of diabetes mellitus but also the leading cause of renal failure. Lotus (Nelumbo nucifera) possesses antioxidative and anticancer properties. The present study aimed to investigate the antidiabetic and renoprotective effects of N. nucifera leaf extract (NLE) in a rat model of type 2 diabetic mellitus. Male Sprague-Dawley rats with type 2 diabetes induced by a high-fat diet (HFD)/streptozotocin (STZ) were treated with NLE at dosages of 0.5% and 1% (w/w) daily for 6 weeks. At the end of the experimental period, body weight, serum glucose levels, insulin levels, and kidney function were assessed. Furthermore, antioxidant enzyme and lipid peroxide levels were determined in the kidney, and histopathological examination was performed using hematoxylin and eosin staining, periodic acid Schiff staining, and Masson trichrome staining. To shed light on the molecular mechanism underlying the functioning of NLE, mouse glomerular mesangial cells (MES-13) treated with high glucose (HG, 25 mM glucose) were chosen as a model for an examination of the signal transduction pathway of NLE. The results revealed that NLE improved diabetic kidney injury by reducing blood glucose, serum creatinine, and blood urea nitrogen levels and enhanced antioxidant enzyme activities in kidney tissue. Treatment with NLE significantly reduced the malondialdehyde and 8-hydroxy-2-deoxyguanosine levels and increased serum insulin levels; expression of renal superoxide dismutase, catalase, and glutathione peroxidase activities; and glutathione content. Histological studies have also demonstrated that NLE treatment inhibited the dilation of Bowman's capsule, which confirmed its renoprotective action in diabetes. In addition, treatment with NLE and its major component quercetin 3-glucuronide attenuated 25 mM HG-induced suppressed nuclear factor erythroid 2-related factor 2 and antioxidant enzyme expression in MES-13 cells. Collectively, these findings indicate that NLE may have antidiabetic and renoprotective effects against HFD/STZ-induced diabetes, at least in part, through antioxidative pathways.
糖尿病肾病不仅是糖尿病常见且严重的微血管并发症，也是肾衰竭的主要原因。莲（Nelumbo nucifera）具有抗氧化和抗癌特性。本研究旨在探讨莲叶提取物（NLE）在高脂饮食（HFD）/链脲佐菌素（STZ）诱导的 2 型糖尿病大鼠模型中的抗糖尿病和肾脏保护作用。雄性 Sprague-Dawley 大鼠通过高脂肪饮食（HFD）/链脲佐菌素（STZ）诱导 2 型糖尿病，用 NLE 以 0.5%和 1%（w/w）的剂量每天治疗 6 周。在实验期末，评估体重、血清葡萄糖水平、胰岛素水平和肾功能。此外，还测定了肾脏中的抗氧化酶和脂质过氧化物水平，并通过苏木精和伊红染色、过碘酸希夫染色和 Masson 三色染色进行了组织病理学检查。为了阐明 NLE 作用的分子机制，选择高糖（25mM 葡萄糖）处理的小鼠肾小球系膜细胞（MES-13）作为模型，研究 NLE 的信号转导途径。结果表明，NLE 通过降低血糖、血清肌酐和血尿素氮水平以及增强肾脏组织中的抗氧化酶活性来改善糖尿病肾脏损伤。NLE 治疗还显著降低了丙二醛和 8-羟基-2-脱氧鸟苷水平，增加了血清胰岛素水平；表达肾脏超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性；以及谷胱甘肽含量。组织学研究还表明，NLE 治疗抑制了鲍曼氏囊的扩张，证实了其在糖尿病中的肾脏保护作用。此外，NLE 和其主要成分槲皮素 3-葡萄糖醛酸苷的治疗减轻了 25mM HG 诱导的 MES-13 细胞中核因子红细胞 2 相关因子 2 和抗氧化酶表达的抑制。综上所述，这些发现表明，NLE 可能具有抗糖尿病和肾脏保护作用，可预防 HFD/STZ 诱导的糖尿病，至少部分通过抗氧化途径。
