Curcumin Suppresses Apoptosis and Inflammation in Hypoxia/Reperfusion-Exposed Neurons via Wnt Signaling Pathway

Abstract

Background: Cerebral ischemia/reperfusion (I/R) injury contributes to mortality and morbidity in preterm infants. Curcumin has been shown to exert neuro-protective effects in the central nervous system (CNS). The aim of this study was to investigate the neuro-protective activity of curcumin and the possible underlying molecular mechanisms. Material/Methods: A hypoxia/reoxygenation (H/R) protocol was used to simulate I/R injury in vitro. Isolated neonatal neurons were pre-treated with curcumin at serially diluted concentrations and exposed to H/R injury. Cell viability and apoptosis were assessed by MTT and flow cytometry, respectively. Contents of TNFa and IL6 in supernatant of cell culture medium were detected by ELISA. Protein expression, phosphorylation, and nuclear translocation levels were studied by Western blotting. Results: H/R reduced cell viability and increased apoptosis of neurons. H/R significantly increased Wnt5a expression, JNK1 phosphorylation, and NF-kB nuclear translocation. Moreover, expression levels of cleaved caspase3, TNFa, and IL6 were elevated in H/R-exposed neurons. Curcumin pre-treatment significantly increased cell viability and inhibited apoptosis of neurons exposed to H/R, in a concentration-dependent manner. Moreover, curcumin pretreatment significantly decreased expression levels of Wnt5a, IL6, TNFa, and phosphorylation level of JNK1, as well as the nuclear translocation level of NF-kB in H/R-exposed neurons, in a concentration-dependent manner. Conclusions: Curcumin exerted neuro-protective effects against H/R-induced neuron apoptosis and inflammation by inhibiting activation of the Wnt/JNK1 signaling pathway.

Atractylenolide III alleviates isoflurane‐induced injury in rat hippocampal neurons by activating the PI3K/Akt/mTOR pathway

“…A recent study reported that silymarin therapy relieves docetaxel‐induced injury of central nervous system by suppressing inflammation (Yardım et al., 2021). Moreover, the application of curcumin was also found to alleviate damage in neuronal cells by inhibiting inflammation and modulating the Wnt/β‐catenin pathway (Zhou et al., 2020). In this study, inflammatory factors were detected in the serum and brain tissues of rats.…”

From Preclinical Stroke Models to Humans: Polyphenols in the Prevention and Treatment of Stroke

“…Curcumin possesses several beneficial properties that could make it a suitable candidate for stroke prevention or treatment, including anti-inflammatory, antilipemic, antiaggregant, neuroprotective and epigenetic modulatory activities [ 275 ]. Pre- and posthypoxia treatment with curcumin was found to effectively promote neuroprotection in rat neurons challenged with OGD [ 276 ], in neonatal mice subjected to hypoxic–ischemic brain injury [ 277 ], in MCAO rodents [ 278 , 279 , 280 , 281 , 282 , 283 , 284 ] and in stroke-prone spontaneously hypertensive rats [ 285 ].…”

The Role of Supplementation with Natural Compounds in Post-Stroke Patients

“…The main active ingredient of turmeric ( Curcuma longa ) is curcumin, which has strong anti-lipidemic, -inflammatory and -aggregating properties, as well as it is an epigenetic modulator and neuroprotective agent [ 77 ]. Neurorestorative properties of curcumin in I/R injury are well documented [ 78 , 79 , 80 ]. Zhou et al showed that curcumin treatment promoted neuronal viability and inhibited apoptosis.…”

“…Zhou et al showed that curcumin treatment promoted neuronal viability and inhibited apoptosis. In in vitro studies (isolated neonatal neurons), curcumin reduced the expression of IL-6, Wnt5a, TNFα, the level of JNK1 phosphorylation, and the NFκB nuclear translocation [ 78 ]. In turn, Li et al observed that curcumin reduces brain edema, disruption of the BBB, and infarct volume in I/R injury through anti-inflammatory, -oxidative and -apoptotic activities.…”

“…Cont. Reduction of the expression of IL-6, Wnt5a, TNFα, the level of JNK1 phosphorylation, and the NFκB nu-clear translocation Reduction of brain edema, disruption of the BBB, and infarct volume Upregulation of Nrf2 expression Decrease in expression of NFκB, as well as MMP9, intercellular adhesion molecule 1 (ICAM1), and caspase 3 expression[77][78][79][80] Cont.…”