Abstract
Notoginsenoside R1 (NGR1) is a predominant phytoestrogen extracted from Panax notoginseng that has recently been reported to play important roles in the treatment of cardiac dysfunction, diabetic kidney disease, and acute liver failure. Studies have suggested that NGR1 may be a viable treatment of hypoxic-ischemic brain damage (HIBD) in neonates by reducing endoplasmic reticulum stress via estrogen receptors (ERs). However, whether NGR1 has other neuroprotective mechanisms or long-term neuroprotective effects is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL) in 7-day-old postnatal Sprague Dawley (SD) rats followed by exposure to a hypoxic environment were used to mimic an HIBD episode. We assessed the efficacy of NGR1 by measuring neuronal damage with MTT assay and assessed brain injury by TTC staining and brain water content detection 24–48 h after OGD/HIE. Simultaneously, we measured the long-term neurophysiological effects using the beam walking test (5 weeks after HI) and Morris water maze test 5–6 weeks after HI. Expression of PI3K-Akt-mTOR/JNK (24 h after HI or OGD/R) proteins was detected by Western blotting after stimulation with HI, NGR1, LY294002 (PI3K inhibitor), 740Y-P (PI3K agonist), or ICI 182780(estrogen receptors inhibitor). The results indicated that NGR1 exerted neuroprotective effects by inhibiting neuronal apoptosis and promoting cell survival via the PI3K-Akt-mTOR/JNK signaling pathways by targeting ER in neonatal hypoxic–ischemic injury.
Highlights
Hypoxic-ischemic brain damage (HIBD) in neonates is an important risk factor for many severe human neurological dysfunctions, such as motor and learning disabilities, cerebral palsy, epilepsy, and even death [1,2,3]
We investigated the neuroprotective effects of Notoginsenoside R1 (NGR1) in a neonatal HIBD model, especially concerned whether NGR1 had a contribution to the long-term recovery of neurological function in the hypoxic–ischemic encephalopathy (HIE)
As the main component of the phytoestrogen from P. notoginseng, NGR1 protected the cortical neurons from injury induced by oxygen glucose deprivation/reoxygenation (OGD/R), but this effect could be blocked by estrogen receptors (ERs) blocker ICI 182780
Summary
Hypoxic-ischemic brain damage (HIBD) in neonates is an important risk factor for many severe human neurological dysfunctions, such as motor and learning disabilities, cerebral palsy, epilepsy, and even death [1,2,3]. It is worth noting that neonatal HIBD often leads to long-lasting neurological deficits such as mental deficiency, cerebral palsy, and learning disabilities, which develop in the immature brain. These consequences have seriously affected the quality of life of children with HIE. Whether NGR1 treatment can promote the long-term recovery of neurological function after HIBD has not yet been reported and is worth exploring
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