Prunus cerasoides Extract and Its Component Compounds Upregulate Neuronal Neuroglobin Levels, Mediate Antioxidant Effects, and Ameliorate Functional Losses in the Mouse Model of Cerebral Ischemia

Abstract

Prunus cerasoides (PC) has been reported to have antimicrobial and anti-inflammatory properties, but its potential as a neuroprotective agent in a mouse model of cerebral ischemia has not been explored. Considering neuroglobin (Ngb), an endogenous neuroprotective factor, as a novel approach to neuroprotection, in this study, Ngb promoter activity, Ngb expression changes, and antioxidant protection by PC extract (PCE) and PC component compounds (PCCs) were analyzed in oxygen–glucose deprivation (OGD)-treated neurons. In vivo analysis involved transient middle cerebral artery occlusion (tMCAO) in mice with pre- and post-treatment exposure to PCE. Following ischemic stroke induction, neurological behavior scores were obtained, and cellular function-related signals were evaluated in the ischemic infarct areas. In addition to PCE, certain component compounds from PCE also significantly increased Ngb levels and attenuated the intracellular ROS production and cytotoxicity seen with OGD in primary neurons. Administration of PCE reduced the infarct volume and improved neurological deficit scores in ischemic stroke mice compared with the vehicle treatment. Increased Ngb levels in infarct penumbra with PCE treatment were also accompanied by decreased markers of apoptosis (activated p38 and cleaved caspase-3). Our findings point to the benefits of Ngb-mediated neuroprotection via PCE and its antioxidant activity in an ischemic stroke model.

Distribution of Neuroglobin in Pericytes is Associated with Blood-Brain Barrier Leakage against Cerebral Ischemia in Mice

“…In the tMCAO group, Ngb was decreased in the core of the cerebral infarct compared with the sham group, but levels of Ngb increased in the penumbra (peripheral tissue of the core). Moreover, after stroke, the Ngb around blood vessels was detached from the NVU in the core and was observed to be increased in neurons [ 17 ]. In the penumbra of tMCAO, although less than that in the sham group, there was a larger amount of Ngb around the blood vessel compared with that in the core ( Fig.…”

“…was detached from the NVU in the core and was observed to be increased in neurons [17]. In the penumbra of tMCAO, although less than that in the sham group, there was a larger amount of Ngb around the blood vessel compared with that in the core (Fig.…”

Neuroprotective Effects of Aucubin against Cerebral Ischemia and Ischemia Injury through the Inhibition of the TLR4/NF-κB Inflammatory Signaling Pathway in Gerbils

“…In recent decades, bioactive compounds derived from medicinal plants have gained significant attention for their diverse biological and pharmacological effects, as well as their safety aspects, in the prevention and treatment of neurological disorders [ 22 ]. Many experimental studies have demonstrated that these compounds exert beneficial effects against cerebral IR injury [ 23 , 24 ]. In this study, we examined the potential neuroprotective effects of AU in a gerbil model of cerebral IR using NeuN immunofluorescence and FJC histofluorescence staining and found that pretreatment with 10 mg/kg of AU, an iridoid glycoside, effectively protected pyramidal neurons, principal neuronal cells, in the hippocampal CA1 field from cerebral IR injury.…”

Neuroglobin protects against cerebral ischemia/reperfusion injury in rats by suppressing mitochondrial dysfunction and endoplasmic reticulum stress‐mediated neuronal apoptosis through synaptotagmin‐1

“…However, Ngb knockdown exhibited the contrary effects. Ngb, a well‐characterized neuroprotectant, can protect neurons from apoptosis and scavenge ROS against oxidative damage, 41 which probably protects neurons from apoptosis following traumatic injury via regulating the Bax/Bcl‐2 pathway 42 . Furthermore, Ngb overexpression attenuates I/R‐induced neuronal injury and improves cell survival under ischemic injury 43 .…”