Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation.
Zefeng WangSongxue GuoJunxing WangYuanyuan ShenJianmin ZhangQun WuPublished in: Scientific reports (2017)
Early brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.
Keyphrases
- subarachnoid hemorrhage
- brain injury
- oxidative stress
- cerebral ischemia
- nlrp inflammasome
- high dose
- cell death
- pi k akt
- cell cycle arrest
- signaling pathway
- traumatic brain injury
- low dose
- poor prognosis
- blood brain barrier
- cardiovascular disease
- long non coding rna
- multiple sclerosis
- lps induced
- type diabetes
- risk factors
- nitric oxide
- coronary artery disease
- stem cell transplantation
- hydrogen peroxide
- reactive oxygen species