■中风是全球死亡率和发病率的主要原因,缺乏有效的预防脑缺血患者脑损伤的治疗策略。具有神经保护活性的中药可能是有益的,并为脑缺血提供了替代治疗机会。
■本研究旨在评估Gueichih-Fuling-Wan(GFW)的神经保护作用和可能的机制,它的组成草药,和它们的活性化合物对脑缺血/再灌注(I/R)引起的啮齿动物脑损伤的影响。
■各种剂量的GFW提取物(0.25、0.5和1.0g/kg)和五种成分草药(肉桂,CC;茯苓,PC;白芍,PL;牡丹,PS和Perisica,PP)口服给药。不同剂量的GFW活性化合物(0.5、1.0和2.0mg/kg),如肉桂醛,肉桂酸(来自CC),芍药苷(来自PL),腹膜内给予丹皮酚(来自PS)。评估了它们对脑缺血/再灌注(I/R)引起的啮齿动物脑损伤的影响。
■GFW,其组成草药,和活性化合物剂量依赖性地减少梗死面积(***P<0.001)。肉桂醛显示最显著的降低(***P<0.001)。因此,反式肉桂醛(TCA)进一步用于评估I/R诱导的脑损伤的神经保护机制。TCA(10、20、30mg/kg,p.o.)以剂量依赖的方式显示出对I/R诱导的小鼠脑损伤的抑制作用。此外,GFW和TCA剂量依赖性地降低COX-2蛋白表达水平,TCA降低了TUNEL(+)细胞凋亡。TCA剂量依赖性增加促存活NR2A和Bcl-2蛋白表达水平,降低促凋亡NR2B和细胞色素c,胱天蛋白酶9和胱天蛋白酶3表达(***P<0.001)。
■上述数据显示,GFW,其组成草药,和活性化合物在啮齿动物中保护免受I/R诱导的脑损伤。来自CC的TCA可能通过抑制神经炎症和凋亡而参与GFW保护脑缺血引起的脑损伤。
UNASSIGNED: Stroke is the leading cause of mortality and morbidity worldwide, and an effective therapeutic strategy for the prevention of patients with
cerebral ischemia induced brain injury is lacking. Traditional Chinese medicine with neuroprotective activities might be beneficial and provide alternative therapeutic opportunities for
cerebral ischemia.
UNASSIGNED: This study aimed to evaluate the neuroprotection and possible mechanisms of Gueichih-Fuling-Wan (GFW), its\' constitutive herbs, and their active compounds on
cerebral ischemia/reperfusion (I/R)-induced brain injury in rodents.
UNASSIGNED: Various doses of extracts (0.25, 0.5, and 1.0 g/kg) of GFW and five constituent herbs (Cinnamomi Cortex, CC; Poria cocos, PC; Paeonia lactifloa, PL; Paeonia suffruticosa, PS and Prunus perisica, PP) were orally administered. Different doses of active compounds (0.5, 1.0, and 2.0 mg/kg) of GFW such as cinnamaldehyde, cinnamic acid (from CC), paeoniflorin (from PL), and paeonol (from PS) were intraperitoneally administered. Their effects on
cerebral ischemia/ reperfusion (I/R)induced brain injury in rodents were evaluated.
UNASSIGNED: GFW, its\' constituent herbs, and the active compounds reduced the infarct area dose-dependently (***P < 0.001). Cinnamaldehyde showed the most significant reduction (***P < 0.001). Therefore, trans-cinnamaldehyde (TCA) was further used to evaluate the neuroprotective mechanism of the I/R-induced brain injury. TCA (10, 20, 30 mg/ kg, p.o.) showed an inhibitory effect of I/R-induced brain damage in mice in a dose-dependent manner. Besides, GFW and TCA dose-dependently reduced the COX-2 protein expression level, and TCA reduced the TUNEL (+) apoptosis. TCA dose-dependently increased the pro-survival NR2A and Bcl-2 protein expression level and decreased the pro-apoptotic NR2B and cytochrome c, caspase 9, and caspase 3 expression (***P < 0.001).
UNASSIGNED: The above data revealed that GFW, its\' constituent herbs, and active compounds protected against I/R-induced brain injury in rodents. TCA from CC might participate in GFW protecting against
cerebral ischemia-induced brain injury by inhibiting neuroinflammation and apoptosis.