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Original Article

Korean J Physiol Pharmacol 2020; 24(5): 423-431

Published online September 1, 2020 https://doi.org/10.4196/kjpp.2020.24.5.423

Copyright © Korean J Physiol Pharmacol.

Curcumin targets vascular endothelial growth factor via activating the PI3K/Akt signaling pathway and improves brain hypoxic-ischemic injury in neonatal rats

Jia Li1,#, Yan An3,#, Jia-Ning Wang2,*, Xiao-Ping Yin2, Huan Zhou2, and Yong-Sheng Wang4

1Department of Otolaryngology Head and Neck Surgery, The Second Hospital of Baoding, Baoding 071000, 2Department of Radiology, Affiliated Hospital of Hebei University, Baoding 071000, 3Department of Obstetrics, Affiliated Hospital of Hebei University, Baoding 071000, 4Department of MR Room, Qingyuan District People’’s Hospital, Baoding 071000, China

Correspondence to:Jia-Ning Wang
E-mail: wangjianing_med@163.com
#These authors contributed equally to this work.

Received: March 17, 2020; Revised: May 22, 2020; Accepted: May 22, 2020

This is an Open Access journal distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aimed to evaluate the effect of curcumin on brain hypoxicischemic (HI) damage in neonatal rats and whether the phosphoinositide 3-kinase (PI3K)/Akt/vascular endothelial growth factor (VEGF) signaling pathway is involved. Brain HI damage models were established in neonatal rats, which received the following treatments: curcumin by intraperitoneal injection before injury, insulin-like growth factor 1 (IGF-1) by subcutaneous injection after injury, and VEGF by intracerebroventricular injection after injury. This was followed by neurological evaluation, hemodynamic measurements, histopathological assessment, TUNEL assay, flow cytometry, and western blotting to assess the expression of p-PI3K, PI3K, p-Akt, Akt, and VEGF. Compared with rats that underwent sham operation, rats with brain HI damage showed remarkably increased neurological deficits, reduced right blood flow volume, elevated blood viscosity and haematocrit, and aggravated cell damage and apoptosis; these injuries were significantly improved by curcumin pretreatment. Meanwhile, brain HI damage induced the overexpression of p-PI3K, p-Akt, and VEGF, while curcumin pretreatment inhibited the expression of these proteins. In addition, IGF-1 treatment rescued the curcumin-induced down-regulated expression of p- PI3K, p-Akt, and VEGF, and VEGF overexpression counteracted the inhibitory effect of curcumin on brain HI damage. Overall, pretreatment with curcumin protected against brain HI damage by targeting VEGF via the PI3K/Akt signaling pathway in neonatal rats.

Keywords: Brain, Curcumin, Hypoxic-ischemic, PI3K/Akt signaling pathway, Vascular endothelial growth factor