Traditional Korean Medicine Based Herbal Drug Research Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseongdaero, Yuseong-gu, Daejeon 305-811, South Korea.
Free Radic Biol Med. 2012 Jul 15;53(2):357-65. doi: 10.1016/j.freeradbiomed.2012.04.030. Epub 2012 May 17.
Retinal pericyte loss is one of the histopathological hallmarks of early diabetic retinopathy. Puerarin (4'-7-dihydroxy-8-beta-d-glucosylisoflavone), which is an isoflavone-C-glucoside, causes various pharmacological effects that include antihyperglycemic and anti-inflammatory activities. In the present study, we determined the efficacy and possible mechanism of puerarin on the advanced glycation end product (AGE)-modified bovine serum albumin (BSA)-induced apoptosis of cultured bovine retinal pericytes and rat retinal pericytes in intravitreally AGE-modified rat serum albumin (RSA)-injected eyes. Puerarin significantly inhibited pericyte apoptosis, the generation of reactive oxygen species (ROS), and NADPH oxidase activity by inhibiting the phosphorylation of p47phox and Rac1 which were induced by the AGE-BSA treatment. The puerarin treatment markedly suppressed the activation of nuclear factor-kappaB (NF-κB). In addition, the in vivo apoptosis of the retinal pericyte of rats that was stimulated by the intravitreal injection of AGE-RSA was evidently attenuated by the puerarin treatment. These results demonstrate that puerarin may exert inhibitory effects on AGE-induced pericyte apoptosis by interfering with the NADPH oxidase-related ROS pathways and blocking NF-κB activation, thereby ameliorating retinal microvascular dysfunction.
视网膜周细胞丧失是早期糖尿病性视网膜病变的组织病理学标志之一。葛根素（4'-7-二羟基-8-β-D-葡萄糖基异黄酮）是一种异黄酮 C-葡萄糖苷，具有多种药理作用，包括降血糖和抗炎作用。在本研究中，我们确定了葛根素对牛血清白蛋白（BSA）晚期糖基化终产物（AGE）修饰诱导的培养牛视网膜周细胞和大鼠视网膜周细胞凋亡的疗效和可能机制，并在玻璃体内注射AGE 修饰的牛血清白蛋白（RSA）的大鼠眼内注射 AGE 修饰的大鼠血清白蛋白（RSA）。葛根素通过抑制 AGE-BSA 处理诱导的 p47phox 和 Rac1 磷酸化，显著抑制周细胞凋亡、活性氧（ROS）的产生和 NADPH 氧化酶活性。葛根素处理明显抑制核因子-κB（NF-κB）的激活。此外，玻璃体内注射 AGE-RSA 刺激的大鼠视网膜周细胞的体内凋亡，经葛根素处理明显减弱。这些结果表明，葛根素可能通过干扰 NADPH 氧化酶相关的 ROS 途径和阻断 NF-κB 激活，对 AGE 诱导的周细胞凋亡发挥抑制作用，从而改善视网膜微血管功能障碍。
