Plumbagin inhibits neuronal apoptosis, intimal hyperplasia and also suppresses TNF-α/NF-κB pathway induced inflammation and matrix metalloproteinase-2/9 expression in rat cerebral ischemia

Abstract

Cerebral ischemic damage and infarction are well documented in stroke, which is presenting a foremost health concern globally with very high mortality and morbidity rates. Mechanisms that are associated with excitotoxicity, inflammation and oxidative stress are found to be critically involved in ischemic damage. Adverse effects of current therapies are imposing the need in development of neuroprotective agents that are very effective. To explore this we experimentally induced ischemic brain injury and investigated the effects of plumbagin. Induction of cerebral infarction and ischemia-reperfusion (I/R) was done by middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Plumbagin (50, 100 or 200 mg/kg b.wt) was intragastrically administered for 9 days before ischemia induction and an hour prior on the day of ischemic insult. Plumbagin treatment attenuated pulmonary edema, neuronal apoptosis and reduced cerebral infarct volume. Cleaved caspase-3 and apoptotic cascade protein expressions were regulated. Overproduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and nitric oxide (NO) following I/R were reduced. Prior plumbagin administration had down-regulated NF-κB signalling and MMP-2 and MMP-9 expression. Overall, the results reveal the potent neuroprotective efficacy of plumbagin against I/R-induced brain injury via effectively modulating apoptotic pathways, MMPs and neuro-inflammatory cascades.

Triticum vulgare Extract Modulates Protein-Kinase B and Matrix Metalloproteinases 9 Protein Expression in BV-2 Cells: Bioactivity on Inflammatory Pathway Associated with Molecular Mechanism Wound Healing

“…Nevertheless, other researchers reported that NF-κB is also involved in molecular pathway of neuronal apoptosis [9] and malaria infection [18]. In these two papers, the scientific evidences reported that NF-κB was associated with MMP9 protein modulation also [9,18]. Our result demonstrated that not only the modulation of p65 in BV-2 cells (Figure 4) but also the modulation of p65 is concurrently associated with MMP9 expression ( Figure 3).…”

“…So far, it is known that NF-κB plays a pivot role inside the program of transcription activation in different types of pathologies [5,11,16,38]. Nevertheless, other researchers reported that NF-κB is also involved in molecular pathway of neuronal apoptosis [9] and malaria infection [18]. In these two papers, the scientific evidences reported that NF-κB was associated with MMP9 protein modulation also [9,18].…”

“…Looking at the literature regarding the in vitro model simulating the molecular inflammatory mechanism, BV-2 cells [5,9,11,18]. Previously, we demonstrated that this cell culture system modulated inflammatory mediators, such as tumor necrosis factoralpha (TNF-α), interleukin 1beta (IL-1β), nitric oxide (NO), and nuclear factor kappa beta (NF-κB), after LPS stimuli [5].…”

“…The NF-κB pathway is activated in various clinical injury conditions including both injuries and ischemia in the brain [8]. For these reasons, NF-κB expression and its expression in BV-2 cells are often used as the preclinical model of microglia inflammation [9], in which NF-κB nuclear expression regulates several genes involved in inflammatory; the list includes enzymes, cytokines, receptors, and cell adhesion molecules [10]. So far, to investigate in vitro this process, many scientists have used the BV-2 cell cultures, derived from mouse microglia.…”

MiR-324/SOCS3 Axis Protects Against Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury and Regulates Myocardial Ischemia via TNF/NF-κB Signaling Pathway

“…66) TNF-α/NF-κB pathway has been recognized as one of the key pathways in the development of inflammation in many diseases, including MI. 67,68) In addition, an increase TNF-α expression has been reported to induce cardiomyocyte apoptosis, thus exacerbating the myocardial damage. 69) Interestingly, we discovered that TNF-α expression was highly upregulated in H/R model, which was in line with previous research.…”