China Academy of Chinese Medical Sciences, Institute of Basic Theory for Chinese Medicine, Beijing, China.
Pharm Biol. 2022 Dec;60(1):1022-1031. doi: 10.1080/13880209.2022.2070221.
Puerarin (Pue) and tanshinone IIA (Tan IIA) are often used in combination in the treatment of cerebrovascular diseases.
To investigate the neuroprotective effect and synergic mechanism of Pue-Tan IIA on the treatment of ischaemic stroke (IS).
IS was induced in rats by middle cerebral artery occlusion (MCAO). Rats were intraperitoneally injected with Pue (36 mg/kg), Tan IIA (7.2 mg/kg), or Pue-Tan IIA (36 and 7.2 mg/kg) for five times [30 min before ischaemia, immediately after reperfusion (0 h), 24, 48, and 72 h after reperfusion]. After administration, neurological function assessment and histological changes in the brain were performed. S-100β and NSE levels were measured to determine the severity of brain injury. Oxidative stress parameters and inflammatory mediators were measured. The proteins involved in Nrf2/ARE signalling pathway were determined by qRT-PCR and western blot.
After administration, the neurological function scores, infarct volume, S-100β, and NSE levels were significantly reduced in MCAO rats, especially with Pue-Tan IIA treatment ( < 0.05). All treatments increased T-AOC, CAT, SOD, and GSH activities and reduced GSSG activity and MDA, TNF-α, IL-6, ICAM-1, and COX-2 levels in MCAO rats. Pue-Tan IIA significantly increased Nrf2 expression in the nucleus (1.81-fold) and decreased its expression in the cytoplasm (0.60-fold). Pue-Tan IIA significantly increased the expressions of HO-1 (1.87-fold) and NQO1 (1.76-fold) and decreased Keap1 expression (0.39-fold).
The combination of Pue and Tan IIA could alleviate ischaemic brain injury by activating Nrf2/ARE signalling pathway, providing an experimental basis for clinical applications.
葛根素（Pue）和丹参酮 IIA（Tan IIA）常用于联合治疗脑血管疾病。
研究葛根素-丹参酮 IIA （Pue-Tan IIA）治疗缺血性脑卒中（IS）的神经保护作用及协同机制。
采用大脑中动脉闭塞（MCAO）法诱导大鼠 IS。大鼠腹腔注射 Pue（36mg/kg）、Tan IIA（7.2mg/kg）或 Pue-Tan IIA（36 和 7.2mg/kg），共 5 次[缺血前 30min，再灌注即刻（0h），再灌注后 24、48 和 72h]。给药后进行神经功能评估和脑组织学改变，检测 S-100β和 NSE 水平以判断脑损伤严重程度，测定氧化应激参数和炎症介质水平，通过 qRT-PCR 和 Western blot 检测 Nrf2/ARE 信号通路相关蛋白。
给药后，MCAO 大鼠的神经功能评分、梗死体积、S-100β 和 NSE 水平显著降低，尤其是 Pue-Tan IIA 治疗组（<0.05）。所有治疗均能提高 MCAO 大鼠的 T-AOC、CAT、SOD 和 GSH 活性，降低 GSSG 活性和 MDA、TNF-α、IL-6、ICAM-1 和 COX-2 水平。Pue-Tan IIA 能显著增加核内 Nrf2 的表达（1.81 倍），减少胞质内 Nrf2 的表达（0.60 倍）。Pue-Tan IIA 还能显著增加 HO-1（1.87 倍）和 NQO1（1.76 倍）的表达，降低 Keap1 的表达（0.39 倍）。
葛根素和丹参酮 IIA 的联合应用通过激活 Nrf2/ARE 信号通路减轻缺血性脑损伤，为临床应用提供了实验依据。
