School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Qingquan Road 30#, Yantai, Shandong, 264005, People's Republic of China.
Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, Qingquan Road 30#, Yantai, Shandong, 264005, People's Republic of China.
BMC Complement Med Ther. 2020 Jan 23;20(1):20. doi: 10.1186/s12906-019-2738-7.
Danshensu is an active constituent in the extracts of Danshen which is a traditional Chinese medical herb. Rotenone inhibits complex I of the mitochondrial electron transport chain in dopaminergic neurons leading to glutathione (GSH) level reduction and oxidative stress. The aim of this study is to investigate neuroprotective effects of Danshensu on rotenone-induced Parkinson's disease (PD) in vitro and in vivo.
In vitro, SH-SY5Y human neuroblastoma cell line was pretreated with Danshensu and challenged with rotenone. Then the reactive oxygen species (ROS) production was assayed. In vivo, male C57BL/6 mice were intragastrically administered with Danshensu (15, 30, or 60 mg/kg), followed by oral administration with rotenone at a dose of 30 mg/kg. Pole and rotarod tests were carried out at 28 d to observe the effects of Danshensu on PD.
Danshensu repressed ROS generation and therefore attenuated the rotenone-induced injury in SH-SY5Y cells. Danshensu improved motor dysfunction induced by rotenone, accompanied with reducing MDA content and increasing GSH level in striatum. Danshensu increased the number of TH positive neurons, the expression of TH and the dopamine contents. The expressions of p-PI3K, p-AKT, Nrf2, hemeoxygenase (HO-1), glutathione cysteine ligase regulatory subunit (GCLC), glutathione cysteine ligase modulatory subunit (GCLM) were significantly increased and the expression of Keap1 was decreased in Danshensu groups.
The neuroprotective effects of Danshensu on rotenone-induced PD are attributed to the anti-oxidative properties by activating PI3K/AKT/Nrf2 pathway and increasing Nrf2-induced expression of HO-1, GCLC, and GCLM, at least in part.
丹参素是丹参提取物中的一种活性成分，丹参是一种传统的中药。鱼藤酮抑制多巴胺能神经元中线粒体电子传递链复合物 I，导致谷胱甘肽 (GSH) 水平降低和氧化应激。本研究旨在探讨丹参素对鱼藤酮诱导的帕金森病 (PD) 的体外和体内神经保护作用。
体外，用丹参素预处理 SH-SY5Y 人神经母细胞瘤细胞系，然后用鱼藤酮处理。然后测定活性氧 (ROS) 的产生。体内，雄性 C57BL/6 小鼠给予丹参素（15、30 或 60mg/kg）灌胃，然后给予鱼藤酮（30mg/kg）灌胃。在第 28 天进行杆和转棒试验，观察丹参素对 PD 的影响。
丹参素抑制 ROS 的产生，从而减轻鱼藤酮诱导的 SH-SY5Y 细胞损伤。丹参素改善了鱼藤酮诱导的运动功能障碍，同时降低纹状体 MDA 含量，增加 GSH 水平。丹参素增加 TH 阳性神经元数量，增加 TH 和多巴胺含量。丹参素组 p-PI3K、p-AKT、Nrf2、血红素加氧酶 (HO-1)、谷胱甘肽半胱氨酸连接酶调节亚单位 (GCLC)、谷胱甘肽半胱氨酸连接酶调节亚单位 (GCLM) 的表达显著增加，Keap1 的表达减少。
丹参素对鱼藤酮诱导的 PD 的神经保护作用归因于通过激活 PI3K/AKT/Nrf2 通路和增加 Nrf2 诱导的 HO-1、GCLC 和 GCLM 的表达来发挥抗氧化作用，至少部分如此。
