Sinomenine Attenuates Traumatic Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation via Nrf2 Pathway
- 248 Downloads
Traumatic spinal cord injury (SCI) is a devastating condition with few efficacious drugs. Sinomenine, a bioactive alkaloid extracted from medicinal herb, has been used as a treatment of rheumatoid diseases. This present study explored the therapeutic effects of sinomenine on locomotor dysfunction and neuropathology in SCI. Our findings revealed that sinomenine mitigated neurological deficits and enhanced neuronal preservation, paralleled with a reduction of apoptosis. Also, sinomenine significantly reduced inflammatory cytokines and oxidative stress factors. We further examined erythroid-2-related factor 2 (Nrf2) nuclear translocation, which mainly controls the coordinated expression of important antioxidant and detoxification genes. An increase in Nrf2 translocation from cytoplasm to nucleus and Nrf2-mediated transactivation was observed after sinomenine administration. Knocking down Nrf2 by siRNA could counteract sinomenine-mediated anti-oxidant stress and anti-inflammation following H2O2-stimulated and LPS-stimulated PC12 cells. Together, our findings indicated that sinomenine has the potential to be an effective therapeutic agent for SCI by inhibiting inflammation and oxidative stress via Nrf2 activation.
KeywordsSinomenine Spinal cord injury Oxidative stress Inflammation Nrf2
This work was supported by the Science and technology project of the National Natural Science Foundation of China (NO. 81401162), the Public Technology Research Program of Zhejiang Province (LGF18H060011) and Science and Technology Planning Program of Taizhou City (1702KY04).
Compliance with Ethical Standards
Conflict of interest
The authors declare no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- 7.Paterniti I, Impellizzeri D, Di Paola R, Esposito E, Gladman S, Yip P, Priestley JV, Michael-Titus AT, Cuzzocrea S (2014) Docosahexaenoic acid attenuates the early inflammatory response following spinal cord injury in mice: in-vivo and in-vitro studies. J Neuroinflammation 11:6CrossRefGoogle Scholar
- 17.Fabrizio FP, Costantini M, Copetti M, la Torre A, Sparaneo A, Fontana A, Poeta L, Gallucci M, Sentinelli S, Graziano P, Parente P, Pompeo V, De Salvo L, Simone G, Papalia R, Picardo F, Balsamo T, Flammia GP, Trombetta D, Pantalone A, Kok K, Paranita F, Muscarella LA, Fazio VM (2017) Keap1/Nrf2 pathway in kidney cancer: frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma. Oncotarget 8:11187–11198CrossRefGoogle Scholar
- 27.Cai Y, Li J, Zhang Z, Chen J, Zhu Y, Li R, Chen J, Gao L, Liu R, Teng Y (2017) Zbtb38 is a novel target for spinal cord injury. Oncotarget 8:45356–45366Google Scholar
- 28.Yang Y, Wang H, Li L, Li X, Wang Q, Ding H, Wang X, Ye Z, Wu L, Zhang X, Zhou M, Pan H (2016) Sinomenine provides neuroprotection in model of traumatic brain injury via the Nrf2-ARE pathway. Front Neurosci 10:580Google Scholar
- 29.Chen L, Cui H, Fang J, Deng H, Kuang P, Guo H, Wang X, Zhao L (2016) Glutamine deprivation plus BPTES alters etoposide- and cisplatin-induced apoptosis in triple negative breast cancer cells. Oncotarget 7:54691–54701Google Scholar
- 32.Choi JY, Hwang CJ, Lee HP, Kim HS, Han SB, Hong JT (2017) Inhibitory effect of ethanol extract of Nannochloropsis oceanica on lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogensis and memory impairment. Oncotarget 8:45517–45530Google Scholar
- 33.Agostini M, Annicchiarico-Petruzzelli M, Melino G, Rufini A (2016) Metabolic pathways regulated by TAp73 in response to oxidative stress. Oncotarget 7:29881–29900Google Scholar
- 35.Zhang R, Xu M, Wang Y, Xie F, Zhang G, Qin X (2016) Nrf2-a promising therapeutic target for defensing against oxidative stress in stroke. Mol Neurobiol 54:6006–6017Google Scholar
- 37.Zhang Q, Wang J, Zhang C, Liao S, Li P, Xu D, Lv Y, Yang M, Kong L (2016) The components of Huang-Lian-Jie-Du-Decoction act synergistically to exert protective effects in a rat ischemic stroke model. Oncotarget 7:80872–80887Google Scholar
- 42.Kumar H, Jo MJ, Choi H, Muttigi MS, Shon S, Kim BJ, Lee SH, Han IB (2017) Matrix metalloproteinase-8 inhibition prevents disruption of blood-spinal cord barrier and attenuates inflammation in rat model of spinal cord injury. Mol Neurobiol 55:2577–2590Google Scholar