School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
National International Cooperation Base of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China.
Biomed Pharmacother. 2021 Jan;133:111021. doi: 10.1016/j.biopha.2020.111021. Epub 2020 Nov 20.
To observe the brain protective effect of Leonuri Herba Total Alkali (LHA) on cerebral ischemia reperfusion injury in rats, so as to provide basis for clinical research.
Adult male SD rats were randomly assigned into sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, and LHA + MCAO/R group (25 mg/kg, 50 mg/kg, and 100 mg/kg). Fourteen days before MCAO/R surgery, the rats in treatment groups were orally administered with LHA in ultrapure water once daily for 14 days, while rats in the sham and MCAO groups were given the same amount of saline in advance. After 1 h of administration on the 14th day, MCAO surgery was subjected. The neurological deficits, brain infarct volume, histopathology, immunofluorescence, inflammation indicators and the gene/protein expressions of BDNF-TrKB-PI3K/Akt signaling pathway in the rat brain tissue were evaluated 24 h after the MCAO/R-injury.
It was found that rats in LHA pre-administration group showed significantly reduced neurological deficit scores, infarction volume, the serum levels of NSE and S100β. Meanwhile, the content of Evans Blue (EB) in brain tissue from LHA group was decreased, as well as the levels of inflammatory cytokines and their gene levels. Moreover, LHA pre-administration inhibited the expression of CD44, GFAP, FOXO1 and promoted the expression of BDNF and NeuN. In addition, LHA pre-administration could up-regulate the protein expression of TrkB, p-PI3K, p-Akt, Bcl-2, and down-regulate the protein expression of Bax, and increase the level of Bcl-2/Bax.
The study demonstrated that LHA pre-administration could regulate the PI3K/Akt pathway by increasing BDNF levels, and play a neuroprotective role in cerebral ischemia-reperfusion injury.
观察益母草总碱（LHA）对大鼠脑缺血再灌注损伤的脑保护作用，为临床研究提供依据。
将成年雄性 SD 大鼠随机分为假手术组、大脑中动脉闭塞/再灌注（MCAO/R）组和 LHA+MCAO/R 组（25、50 和 100mg/kg）。在 MCAO/R 手术前 14 天，治疗组大鼠每日用超纯水口服 LHA，连续 14 天，而假手术和 MCAO 组大鼠则预先给予相同量的生理盐水。在第 14 天给药 1 小时后，进行 MCAO 手术。在 MCAO/R 损伤后 24 小时，评估大鼠的神经功能缺损、脑梗死体积、组织病理学、免疫荧光、炎症指标以及大鼠脑组织中 BDNF-TrKB-PI3K/Akt 信号通路的基因/蛋白表达。
发现 LHA 预处理组大鼠的神经功能缺损评分、梗死体积、血清 NSE 和 S100β 水平明显降低。同时，LHA 组脑组织中 Evans Blue（EB）含量降低，炎症细胞因子及其基因水平降低。此外，LHA 预处理抑制了 CD44、GFAP、FOXO1 的表达，促进了 BDNF 和 NeuN 的表达。此外，LHA 预处理可以上调 TrkB、p-PI3K、p-Akt、Bcl-2 的蛋白表达，下调 Bax 的蛋白表达，并增加 Bcl-2/Bax 的水平。
该研究表明，LHA 预处理可以通过增加 BDNF 水平来调节 PI3K/Akt 通路，在脑缺血再灌注损伤中发挥神经保护作用。
