Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Biol Pharm Bull. 2011;34(8):1319-24. doi: 10.1248/bpb.34.1319.
Ginsenoside Rb1 (GRb1) has been shown to benefit many central nervous system (CNS) disorders, including stroke. However, its bioavailability is low after oral administration due to poor absorption. Intranasal administration has been considered as an effective method for central nervous system drug delivery for its brain-targeting effect. Here, whether intranasal GRb1 could ameliorate cerebral ischemia/reperfusion injury was investigated. First, the concentration of GRb1 in brain tissues and plasma after intranasal and intravenous delivery was calculated using HPLC-MS/MS methods in male Sprague-Dawley rats (250±10 g). Intranasal GRb1 was considered brain-targeting if the value of the drug targeting index (DTI) was greater than 1. Rats were subjected to 1.5 h middle cerebral artery occlusion (MCAO) and were killed 24 h after reperfusion. The neuroprotective effects were measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining. Immunoblotting of LC3 and Beclin 1, crucial autophagy-related proteins, was used to monitor the state of autophagy. With a local bioavailability of 10.28-32.48% and DTI of 7.35-23.22 in different brain regions, intranasal GRb1 was determined to be brain-targeting. Less infarct volume and more intact neuronal structure were observed in the GRb1 group. GRb1 also restored the elevation of LC3 and Beclin 1. Our work suggests that intranasal GRb1 exerts brain-targeting effects and that a single dose of intranasal GRb1 immediately after MCAO ameliorates ischemia/reperfusion insult. Autophagy is involved in these beneficial effects.
人参皂苷 Rb1（GRb1）已被证明对许多中枢神经系统（CNS）疾病有益，包括中风。然而，由于吸收不良，其口服生物利用度较低。由于具有靶向大脑的作用，鼻内给药已被认为是一种有效的中枢神经系统药物递送方法。在这里，研究了鼻内 GRb1 是否可以改善脑缺血/再灌注损伤。首先，使用 HPLC-MS/MS 方法在雄性 Sprague-Dawley 大鼠（250±10 g）中计算了脑内和血浆中 GRb1 的浓度。如果药物靶向指数（DTI）的值大于 1，则认为鼻内 GRb1 具有靶向大脑的作用。大鼠接受 1.5 h 大脑中动脉闭塞（MCAO），再灌注后 24 h 处死。使用 2,3,5-三苯基氯化四氮唑（TTC）染色和尼氏染色测量神经保护作用。使用关键的自噬相关蛋白 LC3 和 Beclin 1 的免疫印迹监测自噬状态。在不同的脑区，GRb1 的局部生物利用度为 10.28-32.48%，DTI 为 7.35-23.22，被确定为具有靶向大脑的作用。GRb1 组的梗死体积更小，神经元结构更完整。GRb1 还恢复了 LC3 和 Beclin 1 的升高。我们的工作表明，鼻内 GRb1 具有靶向大脑的作用，MCAO 后立即给予单剂量鼻内 GRb1 可改善缺血/再灌注损伤。自噬参与了这些有益作用。
