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芍药苷和毛蕊异黄酮-7-O-葡萄糖苷通过 PI3K/AKT 信号通路减轻缺血性脑卒中损伤。

Combination of paeoniflorin and calycosin-7-glucoside alleviates ischaemic stroke injury via the PI3K/AKT signalling pathway.

机构信息

College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangdong, China.

出版信息

Pharm Biol. 2022 Dec;60(1):1469-1477. doi: 10.1080/13880209.2022.2102656.

Abstract

CONTEXT

Paeoniflorin (PF) and calycosin-7-glucoside (CG, Pall. extract) have demonstrated protective effects in ischaemic stroke.

OBJECTIVE

To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury and .

MATERIALS AND METHODS

Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed . Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO for 6 h. SOD, MDA, ROS, LDH and protein levels were measured .

RESULTS

PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression and , and reduced GSK-3β (10.5%, 9.6%) expression. , PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively).

CONCLUSIONS

PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.

摘要

上下文

芍药苷(PF)和毛蕊异黄酮-7-葡萄糖苷(CG,白头翁提取物)已被证明对缺血性中风具有保护作用。

目的

研究 PF+CG 对缺血/再灌注损伤的协同作用。

材料和方法

雄性 Sprague-Dawley 大鼠进行大脑中动脉闭塞/再灌注(MCAO/R)。MCAO/R 24 小时后,大鼠随机分为 5 组:假手术(Sham)、模型(MCAO/R)、研究治疗(PF+CG,40+20mg/kg)、LY294002(20mg/kg)和研究治疗+LY294002。雄性大鼠通过灌胃给药;实验持续 8 天。评估神经功能缺损、脑梗死、脑水肿和蛋白水平。将海马神经元(HT22)用无糖 DMEM 刷新,并在厌氧室中放置 8 小时。随后,HT22 细胞在 37°C 孵育箱中用 5%CO 再氧合 6 小时。测量 SOD、MDA、ROS、LDH 和蛋白水平。

结果

与 MCAO/R 组相比,PF+CG 显著降低神经行为学结果(21%)、脑梗死体积(44%)和脑水肿(1.6%)。此外,PF+CG 增加了 p-PI3K/PI3K(4.69%,7.4%)、p-AKT/AKT(6.25%,60.6%)和 Bcl-2/BAX(33%,49%)的表达,并降低了 GSK-3β(10.5%,9.6%)的表达。在 HT22 细胞中,PF+CG 抑制了细胞凋亡,降低了 ROS 和 MDA 水平(分别为 20%和 50%)。

结论

PF+CG 对缺血性脑损伤表现出协同保护作用,可能成为缺血性中风的未来治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10db/9361763/9e6b897f36eb/IPHB_A_2102656_F0001_C.jpg

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