Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System
Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System
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青藤碱通过 ROS 依赖性上调内源性抗氧化系统，保护 PC12 神经元细胞免受 H2O2 诱导的细胞毒性和氧化应激
DOI：
10.1007/s10571-017-0469-1
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发表时间：
2017-11-01
影响因子：
4
通讯作者：
Li, Juan
中科院分区：
文献类型：
--
作者：
Fan, Hua;Shu, Qing;Li, Juan
青藤碱（Sinomenine，SN）是从中药青风藤（Sinomeniumacutum）中提取的一种生物碱，具有神经保护和抗炎作用。有研究表明，SN的抗氧化特性，主要通过抑制NADPH氧化酶的激活，参与了SN的有益作用。然而，SN属于右旋吗啡喃类似物家族，其可引发活性氧（ROS）水平升高。因此，在本报告中，我们进行了研究，以检查其对PC 12神经元细胞抗氧化应激的影响和机制。SN（0.1-5 μM）预处理12 h可显著降低H2 O2诱导的细胞毒性，并显著减轻氧化损伤。然而，SN在体外几乎没有直接清除自由基的能力，并诱导PC 12细胞产生“适当”的ROS。有趣的是，SN触发的ROS产生充当激活Nrf 2抗氧化系统的信号，包括Nrf 2，HO-1和NQO-1，其被抗氧化剂trolox抑制。此外，Nrf 2敲低在很大程度上减弱了SN预处理对氧化应激的有益作用。结论：SN通过ROS依赖性上调内源性抗氧化系统，增强神经细胞对氧化应激的抵抗力，其机制可能与SN的神经保护作用有关。
Sinomenine (SN), a purified alkaloid from Chinese herbSinomenium acutumthat was used preferentially in the treatment of rheumatoid diseases, has exerted neuroprotective effects and anti-inflammatory properties in many previous studies. Some studies have revealed that the antioxidant property of SN, acting mainly through inhibiting NADPH oxidase activation, was involved in the beneficial effects of SN. However, SN belongs to the family of dextrorotatory morphinan analogues, which may initiate elevation of reactive oxygen species (ROS) levels. Thus in the present report, we conducted studies to examine its impact and mechanism on the resistance of PC12 neuronal cells to oxidative stress. Precondition with SN (0.1–5 μM) for 12 h significantly decreased H2O2-induced cytotoxicity and remarkably alleviated oxidative injury. However, SN exhibited little direct free radical scavenging property in vitro and induced “appropriate” production of ROS in PC12 cell. Interestingly, the SN-triggering ROS production served as a signal to activate the Nrf2 antioxidant system including Nrf2, HO-1, and NQO-1, which was inhibited by the antioxidant trolox. Furthermore, Nrf2 knockdown largely attenuated the beneficial effects of SN precondition on oxidative stress. In conclusion, our findings suggested that SN increased the resistance to oxidative stress in neuronal cells via a ROS-dependent up-regulation of endogenous antioxidant system, and this mechanism may be involved in the neuroprotection of SN.