Department of Natural Medicinal Chemistry, School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 211198, PR China; Department of TCMs Pharmaceuticals & State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210009, PR China.
Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210009, PR China.
Phytomedicine. 2019 Nov;64:153060. doi: 10.1016/j.phymed.2019.153060. Epub 2019 Jul 29.
Diabetic nephropathy is the most serious complication of diabetes. Cyclocarya paliurus (CP), an herbal plant in China, has been reported the biological activity of anti-hyperglycemia. However, its effects on the diabetic nephropathy (DN) remain unclear.
We aimed to investigate the potential role of CP and its underlying mechanisms on DN.
In this study, the effects of triterpenic acids-enriched fraction from CP (CPT) on DN was evaluated in streptozotocin (STZ)-induced rats and high glucose (HG)-induced HK-2 cells models.
After oral administration with or without CPT for 10 weeks, body weight, glucose, microalbumin, serum creatinine and blood urea in STZ-induced rats were detected. Histological analysis was performed to evaluate renal function of mice. Moreover, the level of autophagy was detected by western blot or immunostaining. In vitro, HG-induced HK-2 cell was conducted to evaluate the renal protection and mechanism of CPT.
CPT dramatically decreased the levels of microalbumin, serum creatinine and blood urea nitrogen and ameliorated increased mesangial matrix and glomerular fibrosis. In addition, we found the CPT prevented renal damage and cell apoptosis through the autophagy. Furthermore, CPT could increase the phosphorylation of AMPK and decrease its downstream effector phosphorylation of mTOR. Besides, the expression of LC3-II were locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C), implying that the autophagy may be regulated with AMPK activation.
These findings suggested that CPT might be a desired candidate against diabetes, potentially through AMPK-mTOR-regulated autophagy pathway.
糖尿病肾病是糖尿病最严重的并发症。中国的一种草本植物青钱柳（CP）已被报道具有抗高血糖的生物活性。然而，其对糖尿病肾病（DN）的作用尚不清楚。
本研究旨在探讨 CP 及其潜在机制在糖尿病肾病中的作用。
在本研究中，评估了 CP 中三萜酸富集部分（CPT）对链脲佐菌素（STZ）诱导的大鼠和高糖（HG）诱导的 HK-2 细胞模型中 DN 的潜在作用。
用或不用 CPT 口服给药 10 周后，检测 STZ 诱导的大鼠的体重、血糖、微量白蛋白、血清肌酐和血尿素。进行组织学分析以评估小鼠的肾功能。此外，通过 Western blot 或免疫染色检测自噬水平。在体外，进行 HG 诱导的 HK-2 细胞实验以评估 CPT 的肾脏保护作用及其机制。
CPT 显著降低了微量白蛋白、血清肌酐和血尿素氮的水平，并改善了系膜基质和肾小球纤维化的增加。此外，我们发现 CPT 通过自噬防止了肾脏损伤和细胞凋亡。此外，CPT 可以增加 AMPK 的磷酸化并降低其下游效应物 mTOR 的磷酸化。此外，LC3-II 的表达被 AMPK 抑制剂 dorsomorphin dihydrochloride（化合物 C）锁定，这表明自噬可能通过 AMPK 激活来调节。
这些发现表明，CPT 可能是一种理想的抗糖尿病候选药物，可能通过 AMPK-mTOR 调节的自噬途径。
