Abstract
Sinomenine (SN), a purified alkaloid from Chinese herb Sinomenium acutum that 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.
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Acknowledgement
This work was supported by the National Nature Science Foundation of China (Grant Nos. U1504808 and 81501075).
Author Contributions
Hua Fan, Qing Shu, and Juan Li conceived and designed the experiments; Xinlei Guan, Jiegang Zhao, Junqiang Yan, Xiangming Li, Jiangbo Liu, Zhaohui Jia, and Jian Shi performed the experiments; Xinlei Guan and Qing Shu analyzed the data; Hua Fan and Juan Li wrote the paper.
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This article does not contain any studies with human participants or animals performed by any of the authors.
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Informed consent was obtained from all individual participants included in the study.
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Hua Fan, Qing Shu and Xinlei Guan have contributed equally to this work.
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Fan, H., Shu, Q., Guan, X. et al. Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System. Cell Mol Neurobiol 37, 1387–1398 (2017). https://doi.org/10.1007/s10571-017-0469-1
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DOI: https://doi.org/10.1007/s10571-017-0469-1