Nakashima Keisuke, Miyashita Hiroyuki, Yoshimitsu Hitoshi, Fujiwara Yukio, Nagai Ryoji, Ikeda Tsuyoshi
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto, 860-0082, Japan.
Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
J Nat Med. 2016 Apr;70(2):290-5. doi: 10.1007/s11418-015-0962-0. Epub 2016 Jan 12.
Because inhibitors of advanced glycation end-products (AGEs), for example pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of lifestyle-related diseases such as diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of N (ε) -(carboxymethyl)lysine (CML) and N (ω) -(carboxymethyl)arginine (CMA) during incubation of collagen-derived gelatin with ribose. Furthermore, compounds with inhibitory effects against CML and CMA formation were isolated from EH. Two new prenylflavonoids (compounds 1 and 2) and two known compounds (3 and 4) were found to significantly inhibit the formation of both CML and CMA; compound 4 (epimedokoreanin B) had the strongest inhibitory effect of the isolated compounds. These data suggest that epimedokoreanin B could prevent clinical complications of diabetes by inhibiting AGEs.
由于晚期糖基化终产物(AGEs)抑制剂,例如吡哆胺,能显著抑制链脲佐菌素诱导的糖尿病大鼠视网膜病变和神经病变的发展,因此使用AGEs抑制剂治疗被认为是预防糖尿病并发症等生活方式相关疾病的一种潜在策略。在本研究中,发现淫羊藿(EH;淫羊藿属植物地上部分)的甲醇提取物在胶原蛋白衍生的明胶与核糖孵育过程中能抑制N(ε)-(羧甲基)赖氨酸(CML)和N(ω)-(羧甲基)精氨酸(CMA)的形成。此外,从EH中分离出了对CML和CMA形成具有抑制作用的化合物。发现两种新的异戊烯基黄酮(化合物1和2)和两种已知化合物(3和4)能显著抑制CML和CMA的形成;化合物4(朝藿定B)在分离出的化合物中具有最强的抑制作用。这些数据表明,朝藿定B可能通过抑制AGEs预防糖尿病的临床并发症。