Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation

Abstract

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.

Nix Plays a Neuroprotective Role in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats

“…Although recent studies have suggested that autophagy is activated after SAH and can ameliorate EBI, the specific mechanism underlying this process remains unknown (Li et al, 2014). As mitochondria are the most important organelles for sources of intracellular energy, mitochondrial dysfunction plays a significant role in EBI after SAH (Wang et al, 2017;Zhou et al, 2017). Mitophagy clears impaired mitochondria in cells.…”

Neuroprotection of mangiferin against oxidative damage via arousing Nrf2 signaling pathway in PC12 cells

“…showed that Mg could increase the activity of Nrf2 through inhibiting the process of ubiquitination degradation in human HL60 cells . Besides, several mechanism studies indicated that Mg displayed its pharmacological properties via activation of Nrf2 . In this study, we employed a series of experiments to explore the neuroprotection of Mg in PC12 cells, a neuron‐like rat pheochromocytoma cell line widely used in the study of cell death and neuronal differentiation.…”

Propoxyphene Mediates Oxyhemoglobin-Induced Injury in Rat Cortical Neurons Through Up-Regulation of Active-β-Catenin

“…Mitochondria are important organelles that participate in many important cellular processes, including the production of ROS, energy metabolism, and apoptosis (Wang et al, 2016). It has been reported that mitochondrial dysfunction participated in the pathological process of SAH models (Chou et al, 2017;Wang Z. et al, 2017). A balance between mitochondrial fusion and fission is crucial to mitochondrial morphology and function (Kawano et al, 1995).…”