Notoginsenoside R1 Alleviates Oxygen–Glucose Deprivation/Reoxygenation Injury by Suppressing Endoplasmic Reticulum Calcium Release via PLC

Abstract

As documented in our previous study, notoginsenoside R1 (NGR1) can inhibit neuron apoptosis and the expression of endoplasmic reticulum (ER) stress-associated pro-apoptotic proteins in hypoxic–ischemic encephalopathy. Recent evidence indicates that the Phospholipase C (PLC)/inositol 1,4,5-trisphosphate receptor (IP3R) is important for the regulation of Ca2+ release in the ER. Ca2+ imbalance can stimulate ER stress, CAMKII, and cell apoptosis. The purpose of this study was to further investigate the neuroprotective effect of NGR1 and elucidate how NGR1 regulates ER stress and cell apoptosis in the oxygen–glucose deprivation/reoxygenation (OGD/R) model. Cells were exposed to NGR1 or the PLC activator m-3M3FBS. Then, IP3R- and IP3-induced Ca2+ release (IICR) and activation of the ER stress and CaMKII signal pathway were measured. The results showed that NGR1 inhibited IICR and strengthened the binding of GRP78 with PERK and IRE1. NGR1 also alleviated the activation of the CaMKII pathway. Pretreatment with m-3M3FBS attenuated the neuroprotective effect of NGR1; IICR was activated, activation of the ER stress and CaMKII pathway was increased, and more cells were injured. These results indicate that NGR1 may suppress activation of the PLC/IP3R pathway, subsequently inhibiting ER Ca2+ release, ER stress, and CaMKII and resulting in suppressed cell apoptosis.

RETRACTED: Notoginsenoside R1 protects human keratinocytes HaCaT from LPS-induced inflammatory injury by downregulation of Myd88

“…7 NGR1 also functions as a neuroprotective effective component in alleviating oxygen-glucose deprivation/reoxygenation injury. 8 Importantly, NGR1 revealed anti-inflammatory effects in multiple situations, such as endotoxin-induced inflammatory in H9c2 cardiomyocytes, 9 oxidized low-density lipoprotein-induced inflammatory in human endothelial EA.Hy926 cells. 10 Due to its strong effects in regulating inflammatory injury, we intended to explore whether NGR1 could have effects in controlling the inflammation of burn injury.…”

Notoginsenoside R1 alleviates high glucose-evoked damage in RSC96 cells through down-regulation of miR-503

“…As mentioned above, both neuroprotective and neurotrophic functions of NGR1 were revealed. These findings were in line with a previous study, in which the neuroprotective function of NGR1 was reported in an oxygen-glucose deprivation/reoxygenation injury model [31].…”

<p>Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases</p>

“…Further study shows that NG-R1 may positively improve the binding of GRP78 to PERK and IRE1α, suppress PLC/IP3R signaling pathway, and decrease cell apoptosis in oxygenglucose deprivation/reoxygenation (OGD/R) rat model. 62 Consistently, NG-R1 protects against brain damage in OGD/ R rat model, upregulates the expression of PI3K/AKT/mTOR signaling pathway, and downregulates JNK signaling pathway by activating estrogen receptors 63 (Figure 2). NG-R1 has been demonstrated to prevent OGD/R-induced oxidative stress by inhibiting the generation of NADPH oxidase-and mitochondria-based superoxide, malondialdehyde, protein carbonyl, and 8-hydroxydeoxyguanosine in vivo and in vitro.…”