Sinomenine Protects PC12 Neuronal Cells against H2O2-induced Cytotoxicity and Oxidative Stress via a ROS-dependent Up-regulation of Endogenous Antioxidant System.
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.
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China. fanhua19851229@126.com.
Hua
H
Fan
Department of Pharmacy, Ninth Hospital of Xi'an, Xi'an, 710054, China.
Qing
Q
Shu
Department of Pharmacy, Wuhan Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Xinlei
X
Guan
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Jiegang
J
Zhao
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Junqiang
J
Yan
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Xiangming
X
Li
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Jiangbo
J
Liu
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Zhaohui
Z
Jia
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Jian
J
Shi
Department of Pharmacy, Tongji Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. lijuan@tjh.tjmu.edu.cn.
Juan
J
Li
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009019:Morphinans / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D009019:Morphinans; D017382:Reactive Oxygen Species; C009271:sinomenine; D006861:Hydrogen Peroxide
Nrf2 antioxidant system; Oxidative stress; ROS-dependent neuroprotection; Sinomenine