Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis

Han, Yuwei; Su, Jingyuan; Liu, Xiujuan; Zhao, Yuan; Wang, Chenchen; Li, Xiaoming

doi:10.1016/j.brainresbull.2016.12.008

Cited by 43 publications

(29 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accumulated studies have shown that TLR4-mediated MAPK signaling pathway plays an important role in eliciting neuroinflammation after SAH (Guo et al, 2016 ; Han et al, 2017 ). It has been determined that MAPK signaling pathway was activated after SAH, leading to production of inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage

Huang

Peng

Pang

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is closely associated with neuroinflammation. Microglial activation is an early event that leads to neuroinflammation after SAH. Peli1 is an E3 ubiquitin ligase that mediates the induction of pro-inflammatory cytokines in microglia. Here we report Peli1 contributions in SAH mediated brain pathology. An SAH model was induced by endovascular perforation in adult male C57BL/6J mice. Peli1 was markedly induced in mice brains in a time-dependent manner and was predominantly expressed in CD16/32-positive microglia after SAH. Using genetic approaches, we demonstrated that decreased Peli1 significantly improved neurological deficits, attenuated brain edema, reduced over-expression of pro-inflammatory cytokine IL-6 and modified apoptotic/antiapoptotic biomarkers. In addition, Peli1 downregulation suppressed ERK and JNK phosphorylation levels via the downregulation of cIAP1/2 expression, subsequently reducing inducible nitric oxide synthase (iNOS) expression after SAH. Therefore, these findings demonstrate that Peli1 contributes to microglia-mediated neuroinflammation in EBI by mediating cIAP1/2 activation, thus promoting the activation of MyD88-dependent MAPK pathway after experimental SAH. Our findings also showed that Peli1 could promote the expression of M1 microglia polarization biomarker CD16/32 and iNOS after SAH. Targeting Peli1 exerts neuroprotective effects during EBI after SAH, thus could provide potential option for prevention-therapy in high-risk individuals.

show abstract

Section: Discussionmentioning

confidence: 99%

Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage

Huang

Peng

Pang

et al. 2017

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The levels of MDA were measured using commercial assay kits (Beyotime Biotechnology, Shanghai, China) according to the instructions provided by the manufacturer as previously described [32] , [33] .…”

Section: Methodsmentioning

confidence: 99%

Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade

et al. 2018

View full text Add to dashboard Cite

Phenotypic switch of vascular smooth muscle cells (VSMCs) is characterized by increased expressions of VSMC synthetic markers and decreased levels of VSMC contractile markers, which is an important step for VSMC proliferation and migration during the development and progression of cardiovascular diseases including atherosclerosis. Chicoric acid (CA) is identified to exert powerful cardiovascular protective effects. However, little is known about the effects of CA on VSMC biology. Herein, in cultured VSMCs, we showed that pretreatment with CA dose-dependently suppressed platelet-derived growth factor type BB (PDGF-BB)-induced VSMC phenotypic alteration, proliferation and migration. Mechanistically, PDGF-BB-treated VSMCs exhibited higher mammalian target of rapamycin (mTOR) and P70S6K phosphorylation, which was attenuated by CA pretreatment, diphenyleneiodonium chloride (DPI), reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC) and nuclear factor-κB (NFκB) inhibitor Bay117082. PDGF-BB-triggered ROS production and p65-NFκB activation were inhibited by CA. In addition, both NAC and DPI abolished PDGF-BB-evoked p65-NFκB nuclear translocation, phosphorylation and degradation of Inhibitor κBα (IκBα). Of note, blockade of ROS/NFκB/mTOR/P70S6K signaling cascade prevented PDGF-BB-evoked VSMC phenotypic transformation, proliferation and migration. CA treatment prevented intimal hyperplasia and vascular remodeling in rat models of carotid artery ligation in vivo. These results suggest that CA impedes PDGF-BB-induced VSMC phenotypic switching, proliferation, migration and neointima formation via inhibition of ROS/NFκB/mTOR/P70S6K signaling cascade.

show abstract

“…Under physiological conditions, redox homeostasis is the result of a balance between the production of reactive oxygen species (ROS) and the action of antioxidant mechanisms. Because even under physiological conditions, the brain has high pro-oxidative potential and high metabolic requirements at the same time, brain is particularly susceptible to oxidative stress [5,6]. The main source of ROS, in the brain, is the leakage of superoxide anions from mitochondria due to an ischemic disruption of the electron transfer chain and the cascade of free radicals produced from the auto-oxidation of hemoglobin, as well as enzymatic reactions [7].…”

Section: Introductionmentioning

confidence: 99%

“…Under physiological conditions, superoxide dismutase is responsible for superoxide dismutation, producing hydrogen peroxide, which is removed by glutathione peroxidase, which prevents the formation of hydroxyl radicals. However, the increase in superoxide dismutase activity relative to glutathione peroxidase in the case of SAH leads to an increase in the level of hydroxyl radicals and increased oxidative processes and modification of cell components, which leads to a disturbance of metabolic pathways and brain signaling [5].…”

Section: Introductionmentioning

confidence: 99%

Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation

et al. 2020

View full text Add to dashboard Cite

Subarachnoid hemorrhage (SAH) accounts for 3% of all strokes. As more and more data indicates the role of oxidative stress in acute brain damage caused by SAH, an attempt was made to correlate the clinical status of patients with systemic level of antioxidants and lipid peroxidation products. The hemorrhage was diagnosed with brain computed tomography (CT) and aneurysm with angio-CT and angiography, while the vasospasm was monitored with transcranial Doppler. Plasma glutathione peroxidase activity (GSH-Px) and vitamin A, E, and C levels were determined spectrophotometrically and by HPLC, respectively. The levels of polyunsaturated fatty acids (PUFAs) cyclization products were determined by GC-MS, while F 2 -isoprostanes and neuroprostanes (NP) were determined by LC-MS. SAH was accompanied by changes in antioxidant capacity in blood plasma, including initially (day 1) an increase in GSH-Px activity, followed by its decrease and a progressive decrease in glutathione (GSH) levels and vitamins A, E, and C. On the other hand, levels of PUFAs cyclization products, F 2 -isoprostanes, and neuroprostanes were highest on day 1 (two and eight times higher, respectively) and decreased over time. The levels of 4-HNE (4-hydroxynonenal), 4-ONE (4-oxononenal), and MDA (malondialdehyde) changed similarly. In contrast, the 4-HHE (4-hydroxyhexenal) level reduced after SAH increased significantly after a week. It was found that the deterioration of the overall clinical and neurological condition of SAH patients due to cerebral edema, intracranial hemorrhage, or vasoconstriction corresponded to reduced antioxidant defense and, as a consequence, increased lipid peroxidation and slower observed changes in regression. It can be concluded that monitoring the level of lipid peroxidation products (neuroprostanes, 4-ONE, and MDA) can support the monitoring of the clinical status of patients, especially with regard to the assessment of vasospasm.

show abstract

Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis

Cited by 43 publications

References 28 publications

Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage

Peli1 Contributions in Microglial Activation, Neuroinflammatory Responses and Neurological Deficits Following Experimental Subarachnoid Hemorrhage

Chicoric acid prevents PDGF-BB-induced VSMC dedifferentiation, proliferation and migration by suppressing ROS/NFκB/mTOR/P70S6K signaling cascade

Clinical Prognosis for SAH Consistent with Redox Imbalance and Lipid Peroxidation

Contact Info

Product

Resources

About