Zhang Yi, Tian Zhiming, Wan Hongyan, Liu Wen, Kong Fanping, Ma Guoping
Cerebral Vascular Center, Zhongda Hospital, Southeast University, Nanjing City, Jiangsu Province 210044, People's Republic of China.
Department of Neurology, Fu-Ning People's Hospital, Yancheng City, Jiangsu Province 224400, People's Republic of China.
Neuropsychiatr Dis Treat. 2020 Mar 31;16:871-879. doi: 10.2147/NDT.S227988. eCollection 2020.
Deltonin, an active component extracted from C.H. WRIGHT, was widely utilized in traditional Chinese medicines. It has been shown to have anti-cancer functions such as colon cancer, breast cancer, and head and neck squamous carcinoma. Herein, we will investigate the role of deltonin in cerebral ischemia/reperfusion injuries.
Ly294002 and anisomycin were used as inhibitors to monitor the effects of deltonin. Middle cerebral artery occlusion I/R model was constructed. Infarct volumes, neurological deficits and brain water contents were evaluated under different conditions. Rotarod test, ELISA, and Western blotting were carried to investigate the effects in vitro.
We found that deltonin in ischemia/reperfusion (I/R) rats greatly enhanced brain damages as well as neurological functions through up-regulating p-Akt and p-mTOR as well as inhibiting the expressions of LC3-II/LC3-I, Beclin-1, IL-1, TLR4, and p-p38. Deltonin exerted neuroprotection effect through relieving autophagy activity by regulating PI3K/Akt/mTOR signaling. Deltonin suppressed inflammation reactions through modulation TLR4/p38/MAPK signaling as well.
Overall, our data suggested that deltonin could suppress ischemic brain injury by regulating autophagy and inflammation during I/R. Deltonin can be a potential therapeutic method for patient with I/R.
德尔托宁是从C.H. 赖特中提取的一种活性成分，在传统中药中被广泛应用。已证明它具有抗癌功能，如对结肠癌、乳腺癌和头颈部鳞状细胞癌。在此，我们将研究德尔托宁在脑缺血/再灌注损伤中的作用。
使用LY294002和茴香霉素作为抑制剂来监测德尔托宁的作用。构建大脑中动脉闭塞I/R模型。在不同条件下评估梗死体积、神经功能缺损和脑含水量。进行转棒试验、酶联免疫吸附测定（ELISA）和蛋白质印迹法来研究体外作用。
我们发现，缺血/再灌注（I/R）大鼠体内的德尔托宁通过上调p-Akt和p-mTOR以及抑制LC3-II/LC3-I、Beclin-1、IL-1、TLR4和p-p38的表达，极大地加重了脑损伤和神经功能障碍。德尔托宁通过调节PI3K/Akt/mTOR信号通路减轻自噬活性，从而发挥神经保护作用。德尔托宁还通过调节TLR4/p38/丝裂原活化蛋白激酶（MAPK）信号通路抑制炎症反应。
总体而言，我们的数据表明，德尔托宁可通过在I/R期间调节自噬和炎症来抑制缺血性脑损伤。德尔托宁可能是治疗I/R患者的一种潜在治疗方法。
