Maternal pomegranate juice attenuates maternal inflammation–induced fetal brain injury by inhibition of apoptosis, neuronal nitric oxide synthase, and NF-κB in a rat model

Ginsberg, Yuval; Khatib, Nizar; Saadi, Noor; Ross, Michael G.; Weiner, Zeev; Beloosesky, Ron

doi:10.1016/j.ajog.2018.04.040

Cited by 23 publications

(18 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Autophagy is a relatively new intracellular organelle process and elucidating the role of autophagy dysregulation in maternal-fetal complications is an important area. Because oxidative stress is involved in many maternal-fetal complications, 21,36–40 investigating oxidative stress-altered autophagy will provide new mechanistic insights on the pathogenesis of these maternal-fetal complications. Immediate future study should also determine if mitigating oxidative stress by either superoxide dismutase 1 in vivo expression or dietary supplements of EGCG or curcumin would restore autophagy in the developing neuroepithelium through inactivation of FoxO3a.…”

Section: Resultsmentioning

confidence: 99%

The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy

Chen

Reece

et al. 2019

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

BACKGROUND: Maternal diabetes induces neural tube defects and stimulates the activity of the forkhead box O3 (Fox)O3a in the embryonic neuroepithelium. We previously demonstrated that deleting the FOXO3a gene ameliorates maternal diabetes-induced neural tube defects. Macroautophagy (hereafter referred to as “autophagy”) is essential for neurulation. Rescuing autophagy suppressed by maternal diabetes in the developing neuroepithelium inhibits neural tube defect formation in diabetic pregnancy. This evidence suggests a possible link between FoxO3a and impaired autophagy in diabetic embryopathy. OBJECTIVE: We aimed to determine whether maternal diabetes suppresses autophagy through FoxO3a, and if the transcriptional activity of FoxO3a is required for the induction of diabetic embryopathy. STUDY DESIGN: We used a well-established type 1 diabetic embryopathy mouse model, in which diabetes was induced by streptozotocin, for our in vivo studies. To determine if FoxO3a mediates the inhibitory effect of maternal diabetes on autophagy in the developing neuroepithelium, we induced diabetic embryopathy in FOXO3a gene knockout mice and FoxO3a dominant negative transgenic mice. Embryos were harvested at embryonic day 8.5 to determine FoxO3a and autophagy activity and at embryonic day 10.5 for the presence of neural tube defects. We also examined the expression of autophagy-related genes. C17.2 neural stem cells were used for in vitro examination of the potential effects of FoxO3a on autophagy. RESULTS: Deletion of the FOXO3a gene restored the autophagy markers, lipidation of microtubule-associated protein 1A/1B-light chain 3I to light chain 3II, in neurulation stage embryos. Maternal diabetes decreased light chain 3I-positive puncta number in the neuroepithelium, which was restored by deleting FoxO3a. Maternal diabetes also decreased the expression of positive regulators of autophagy (Unc-51 like autophagy activating kinase 1, Coiled-coil myosin-like BCL2-interacting protein, and autophagy-related gene 5) and the negative regulator of autophagy, p62. FOXO3a gene deletion abrogated the dysregulation of autophagy genes. In vitro data showed that the constitutively active form of FoxO3a mimicked high glucose in repressing autophagy. In cells cultured under high-glucose conditions, overexpression of the dominant negative FoxO3a mutant blocked autophagy impairment. Dominant negative FoxO3a overexpression in the developing neuroepithelium restored autophagy and significantly reduced maternal diabetes-induced apoptosis and neural tube defects. CONCLUSION: Our study revealed that diabetes-induced FoxO3a activation inhibited autophagy in the embryonic neuroepithelium. We also observed that FoxO3a transcriptional activity mediated the teratogenic effect of maternal diabetes because dominant negative FoxO3a prevents maternal diabetes-induced autophagy impairment and neural tube defect formation. Our findings suggest that autophagy activators could be therapeutically effective in treating maternal diabetes-induced neural tube def...

show abstract

Section: Resultsmentioning

confidence: 99%

The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy

Chen

Reece

et al. 2019

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

show abstract

“…A lot of research on the neuroprotective activity of pomegranate juice and extract has been done. Supplementation with pomegranate juice in the drinking water of pregnant and nursing dams has been demonstrated to protect the neonatal brain in an inflammatory [4] and a hypoxic-ischemic (H-I) models [5,6]. These neuroprotective effects have been shown to be attributed to the inhibition of oxidative stress, and a decrease in the production of proinflammatory cytokines [4] and apoptotic proteins [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Supplementation with pomegranate juice in the drinking water of pregnant and nursing dams has been demonstrated to protect the neonatal brain in an inflammatory [4] and a hypoxic-ischemic (H-I) models [5,6]. These neuroprotective effects have been shown to be attributed to the inhibition of oxidative stress, and a decrease in the production of proinflammatory cytokines [4] and apoptotic proteins [4][5][6]. In adult male rats, pre-administration with pomegranate extract has provided dose-dependent neuroprotection against cerebral ischemia-reperfusion (I/R) brain injury and DNA damage via antioxidant, anti-inflammatory, and anti-apoptotic action [7].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

Kujawska

Jourdes

Kurpik

et al. 2019

IJMS

114

View full text Add to dashboard Cite

Pomegranate juice is a rich source of ellagitannins (ETs) believed to contribute to a wide range of pomegranate’s health benefits. While a lot of experimental studies have been devoted to Alzheimer disease and hypoxic-ischemic brain injury, our knowledge of pomegranate’s effects against Parkinson’s disease (PD) is very limited. It is suggested that its neuroprotective effects are mediated by ETs-derived metabolites—urolithins. In this study, we examined the capability of pomegranate juice for protection against PD in a rat model of parkinsonism induced by rotenone. To evaluate its efficiency, assessment of postural instability, visualization of neurodegeneration, determination of oxidative damage to lipids and α-synuclein level, as well as markers of antioxidant defense status, inflammation, and apoptosis, were performed in the midbrain. We also check the presence of plausible active pomegranate ETs-derived metabolite, urolithin A, in the plasma and brain. Our results indicated that pomegranate juice treatment provided neuroprotection as evidenced by the postural stability improvement, enhancement of neuronal survival, its protection against oxidative damage and α-synuclein aggregation, the increase in mitochondrial aldehyde dehydrogenase activity, and maintenance of antiapoptotic Bcl-xL protein at the control level. In addition, we have provided evidence for the distribution of urolithin A to the brain.

show abstract

“…They conluded that the walnut diet inhibited the expression of NF‐kB, thereby potentially reducing the function of some inflammatory genes such as TNF‐α, COX‐2, interleukin‐1. Ginsberg et al (2018) investigated the anti‐inflammatory, antioxidant and neuroprotective role of pomegranate juice in fetal brain. They found that the NF‐kB protein expression increased in lippolisaccharide group but the NF‐kB protein expression decreased with the pomegranate juice application.…”

Section: Discussionmentioning

confidence: 99%

The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf‐2, NF‐kB and apoptotic pathway

et al. 2020

View full text Add to dashboard Cite

The aim of this study was to investigate the neuroprotective role of ellagic acid (EA) on CCl4‐induced brain injury in rats. In this study, the rats were divided into four groups. Groups: (1) Control group; (2) EA group; (3) CCl4 group; (4) EA + CCl4 group. In brain tissue, tumor necrosis factor‐α (TNF‐α), nuclear factor kappa b (NF‐kB), cyclooxygenase‐2 (COX‐2), nuclear erythroid related factor 2 (Nrf‐2), cysteine‐aspartic acid protease (caspase‐3), VEGF (vascular endothelial growth factor) and B‐cell lymphoma‐2 (bcl‐2) protein expression levels were analyzed by western blotting. MDA (malondialdehyde), catalase enzyme activity (CAT) and glutathione (GSH) analysis were determined by spectrophotometer. In our findings, EA ameliorated Nrf‐2 and caspase‐3 protein expression levels, GSH and catalase activities, NF‐kB, TNF‐α, VEGF, Bcl‐2, COX‐2 protein expression levels and MDA levels in CCl4 intoxicated rats. These results suggest that EA demonstrated the neuroprotective effect on CCl4‐induced brain damage in rats. Practical applications Ellagic acid has different biological activities, these are; antioxidant, anti‐inflammatory, antidepressant, antifibrosis, anticancer, neuroprotective and hepatoprotective. For example it was reported that EA protects the cells against DNA injury induced by free radicals and it can prevent the traumatic brain injury. These results obtained from this study reveals that EA has a protective effect against rat brain damage and it may be used as an alternative drugs for the brain injury treatment in future.

show abstract

Maternal pomegranate juice attenuates maternal inflammation–induced fetal brain injury by inhibition of apoptosis, neuronal nitric oxide synthase, and NF-κB in a rat model

Cited by 23 publications

References 63 publications

The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy

The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy

Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

The preventive effect of ellagic acid on brain damage in rats via regulating of Nrf‐2, NF‐kB and apoptotic pathway

Contact Info

Product

Resources

About