Calenduloside E alleviates cerebral ischemia/reperfusion injury by preserving mitochondrial function

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Cerebral ischemia/reperfusion (I/R) injury is a major cause of stroke, leading to significant neuronal damage.
• Calenduloside E (CE), a saponin from Aralia elata, is known to protect the heart but its effects on the brain are unclear.
• Understanding the mechanisms of CE in neuroprotection is crucial for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the neuroprotective effects and underlying mechanisms of Calenduloside E (CE) against cerebral ischemia/reperfusion (I/R) injury.
• To evaluate CE's impact on neuronal viability, apoptosis, and mitochondrial function in both in vitro and in vivo models of cerebral I/R.

Main Methods:

• Established an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells and a middle cerebral artery occlusion (MCAO) model in mice.
• Assessed cell viability, apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS), and calcium levels.
• Analyzed protein levels of key apoptotic markers (Bax, Bcl-2, Caspases) and mitochondrial proteins (Drp1, Cytochrome C).

Main Results:

• CE significantly improved cell viability and reduced apoptosis in OGD/R-treated HT22 cells.
• CE treatment inhibited mitochondrial fission by modulating Drp1 phosphorylation and recruitment.
• CE preserved mitochondrial function, reduced oxidative stress and calcium overload, and regulated apoptosis-related proteins, leading to decreased infarct volume and improved neurological function in vivo.

Conclusions:

• Calenduloside E (CE) demonstrates significant neuroprotective effects against cerebral ischemia/reperfusion injury.
• CE ameliorates neuronal damage by mitigating mitochondrial dysfunction and apoptosis.
• CE holds promise as a therapeutic agent for treating stroke and related brain injuries.