Naoxintong Protects Primary Neurons from Oxygen‐Glucose Deprivation/Reoxygenation Induced Injury through PI3K‐Akt Signaling Pathway

Abstract

Naoxintong capsule (NXT), developed from Buyang Huanwu Decoction, has shown the neuroprotective effects in cerebrovascular diseases, but the neuroprotection mechanisms of NXT on ischemia/reperfusion injured neurons have not yet been well known. In this study, we established the oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurons injury model and treat the neurons with cerebrospinal fluid containing NXT (BNC) to investigate the effects of NXT on OGD/R induced neurons injury and potential mechanisms. BNC improved neuron viability and decreased apoptotic rate induced by OGD/R. BNC attenuated OGD/R induced cytosolic and mitochondrial Ca2+ overload, ROS generation, intracellular NO levels and nNOS mRNA increase, and cytochrome-c release when compared with OGD/R group. BNC significantly inhibited both mPTP opening and ΔΨm depolarization. BNC increased Bcl-2 expression and decreased Bax expression, upregulated the Bcl-2/Bax ratio, downregulated caspase-3 mRNA and caspase-9 mRNA expression, and decreased cleaved caspase-3 expression and caspase-3 activity. BNC increased phosphorylation of Akt following OGD/R, while LY294002 attenuated BNC induced increase of phosphorylated Akt expression. Our study demonstrated that NXT protected primary neurons from OGD/R induced injury by inhibiting calcium overload and ROS generation, protecting mitochondria, and inhibiting mitochondrial apoptotic pathway which was mediated partially by PI3K-Akt signaling pathway activation.

Naoxintong/PPARγ Signaling Inhibits Cardiac Hypertrophy via Activation of Autophagy

“…As the Chinese herbal compound, the chemical compositions were identified by UPLC/Q-TOF-MS [ 17 ]. In addition, NXT activates PI3K-Akt pathway resulting in inhibition of oxygen-glucose deprivation/reoxygenation-induced neurons damage [ 18 ]. The combination of NXT and dual antiplatelet therapy can reduce coronary microembolization [ 19 ].…”

PI3K/AKT signaling mediated by G protein-coupled receptors is involved in neurodegenerative Parkinson's disease (Review)

“…Therefore, both acute and chronic neurodegenerative disorders could be mainly a result of oxidative stress (10). ROS regulation and inhibition of the apoptotic pathway thereby protecting cells have been shown to be controlled by the PI3K/AKT signaling pathway (11). The mechanism involved in PI3K/AKT activation exhibits stimuli-specific variations.…”

Storax Protected Oxygen-Glucose Deprivation/Reoxygenation Induced Primary Astrocyte Injury by Inhibiting NF-κB Activation in vitro

“…To mimic the impairment of astrocytes in ischemic injury in vivo , we established the OGD/R model in vitro as described previously (Ma et al., 2016). Simply, astrocytes were washed with pre-warmed HBSS twice, and the culture medium was replaced with a glucose-free DMEM, and placed astrocytes in a hypoxic humidified incubator chamber (Stem Cell, Canada) flushed with a gas mixture of 95% N 2 and 5% CO 2 .…”

“…Intracellular ROS level was determined as described previously (Ma et al., 2016). Astrocytes were loaded with 5 μM DCFH-DA at 37°C for 30 min and then washed with D-hank’s three times to remove residual probe.…”