TY - JOUR
T1 - Neuroprotective effects of ellagic acid on neonatal hypoxic brain injury via inhibition of inflammatory mediators and down-regulation of JNK/p38 MAPK activation
AU - Chen, Si Yan
AU - Zheng, Kuang
AU - Wang, Zhi Quan
N1 - Publisher Copyright:
© Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.
PY - 2016/2
Y1 - 2016/2
N2 - Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic-ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post-natal day 10 (D10). On D10, the rats were subjected to HI brain injury. Following HI injury, infarct size, weight and volume of the brain were measured. Apoptosis was assessed by Fluoro-Jade C staining. Expression of caspases (caspase-3, 8 and 9), apoptotic pathway proteins (Bax, Bad, Bcl-2 and Bcl-xL), MAPKs, NF-κB(p65) and p-IK-Bα were assessed by western blotting. mRNA levels of inflammatory mediators (TNF-α, IL-1α, IL-1β, iNOS, COX-2) were analyzed. Results: Ellagic acidmarkedly (p < 0.05) reduced infarct size, volume and tissue loss. Significant (p < 0.05) reduction in neuroapoptosis was observed on pre-treatment with ellagic acid. Expression levels of caspases, apoptotic pathway proteins and MAPK proteins were down-regulated with marked (p < 0.05) suppression of inflammatory mediators, NF-κB(p65) and p-IK-Bα. Conclusion: Ellagic acid affords neuroprotection in HI brain injury by inhibiting apoptosis, inflammatory responses and modulating the proteins of apoptotic and MAPK pathways. Thus, ellagic acid may be a potent candidate for the treatment of HI injury.
AB - Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic-ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post-natal day 10 (D10). On D10, the rats were subjected to HI brain injury. Following HI injury, infarct size, weight and volume of the brain were measured. Apoptosis was assessed by Fluoro-Jade C staining. Expression of caspases (caspase-3, 8 and 9), apoptotic pathway proteins (Bax, Bad, Bcl-2 and Bcl-xL), MAPKs, NF-κB(p65) and p-IK-Bα were assessed by western blotting. mRNA levels of inflammatory mediators (TNF-α, IL-1α, IL-1β, iNOS, COX-2) were analyzed. Results: Ellagic acidmarkedly (p < 0.05) reduced infarct size, volume and tissue loss. Significant (p < 0.05) reduction in neuroapoptosis was observed on pre-treatment with ellagic acid. Expression levels of caspases, apoptotic pathway proteins and MAPK proteins were down-regulated with marked (p < 0.05) suppression of inflammatory mediators, NF-κB(p65) and p-IK-Bα. Conclusion: Ellagic acid affords neuroprotection in HI brain injury by inhibiting apoptosis, inflammatory responses and modulating the proteins of apoptotic and MAPK pathways. Thus, ellagic acid may be a potent candidate for the treatment of HI injury.
KW - Brain injury
KW - Ellagic acid
KW - Hypoxia
KW - Inflammatory mediators
KW - Mitogen-activated protein kinases
KW - Neuroprotective
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U2 - 10.4314/tjpr.v15i2.4
DO - 10.4314/tjpr.v15i2.4
M3 - Article
AN - SCOPUS:84959290019
SN - 1596-5996
VL - 15
SP - 241
EP - 251
JO - Tropical Journal of Pharmaceutical Research
JF - Tropical Journal of Pharmaceutical Research
IS - 2
ER -