College of Pharmacy & Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
Phytomedicine. 2012 Feb 15;19(3-4):217-22. doi: 10.1016/j.phymed.2011.08.064. Epub 2011 Oct 5.
Connective tissue growth factor (CTGF) plays a pathogenic role in diabetic nephropathy (DN). Loganin, an iridoid glucoside compound was isolated from Cornus officinalis Sieb. et Zucc. This study was conducted to investigate the efficacy of loganin on DN and to elucidate the potential mechanism. High glucose (HG) stimulated cultured human renal proximal tubular epithelial cells (HK-2) analyzed CTGF expression by Western blotting and investigated whether extracellular signal-regulated kinase (ERK) signaling pathway was involved. Streptozotocin (STZ)-induced experimental DN, randomized to receive intragastric (i.g.) of loganin. Renal tissue, blood and urine samples were collected to determine and analyze. In vitro study, loganin reduced CTGF excretion in HG-induced HK-2 cells through the ERK signaling pathway. In vivo study, I.g. of loganin 5 mg/kg or 10 mg/kg significantly ameliorated renal function and increased body weight. Meanwhile, loganin reduced renal CTGF expression by immunohistochemical staining, reduced serum levels of CTGF. Besides, there were no significant differences in blood sugar levels between the loganin groups compared to the STZ-treated group. Furthermore, loganin ameliorated renal pathology. These results suggested that loganin exerts an early renal protective role to DN. Inhibition of CTGF may be a potential target in DN therapy, which highlights the possibility of using loganin to treat DN.
结缔组织生长因子（CTGF）在糖尿病肾病（DN）中发挥致病作用。马钱苷是从山茱萸科植物山茱萸中分离得到的环烯醚萜苷类化合物。本研究旨在探讨马钱苷对 DN 的治疗作用，并阐明其潜在机制。高糖（HG）刺激培养的人近端肾小管上皮细胞（HK-2），通过 Western blot 分析 CTGF 的表达，并探讨细胞外信号调节激酶（ERK）信号通路是否参与其中。链脲佐菌素（STZ）诱导的实验性 DN 随机分为马钱苷灌胃组。收集肾组织、血液和尿液样本进行测定和分析。在体外研究中，马钱苷通过 ERK 信号通路减少 HG 诱导的 HK-2 细胞中 CTGF 的排泄。在体内研究中，马钱苷 5mg/kg 或 10mg/kg 灌胃显著改善肾功能，增加体重。同时，马钱苷通过免疫组化染色减少肾 CTGF 表达，降低血清 CTGF 水平。此外，与 STZ 处理组相比，马钱苷组的血糖水平无显著差异。此外，马钱苷还改善了肾脏病理。这些结果表明，马钱苷对 DN 具有早期的肾脏保护作用。抑制 CTGF 可能是 DN 治疗的潜在靶点，这凸显了使用马钱苷治疗 DN 的可能性。
