Protective effect of phillyrin against cerebral ischemia/reperfusion injury in rats and oxidative stress-induced cell apoptosis and autophagy in neurons

Abstract

This study explored the role and potential molecular mechanism of phillyrin in cerebral ischemia/reperfusion (I/R) injury. The rat middle cerebral artery occlusion (MCAO)/R model was constructed, and cerebral infarction volume, brain water content, and neurological score were measured. Neuron morphological structures in brain tissues and primary neuron apoptosis were detected using hematoxylin and eosin (H&E) staining and Hoechst 33258 staining, respectively. In MCAO/R rats, phillyrin markedly reduced cerebral infarction volume, neurological score, and brain water content and inhibited neuron apoptosis. In vitro experiments showed that phillyrin remarkably increased viability and decreased lactate dehydrogenase (LDH) release of H 2 O 2 -injured neurons. Moreover, phillyrin remarkably downregulated the proportion of apoptosis-related protein B-associated X (Bax)/B-cell lymphoma protein 2 (Bcl-2) and reduced procaspase-3, phospho-Akt (p-Akt-1), and phosphorylation-mammalian target of rapamycin (p-mTOR) levels in H 2 O 2 -injured neurons. Furthermore, phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 weakened the effects of phillyrin on p-mTOR, p-Akt-1, characteristic proteins of autophagy 3-II (LC3-II) and beclin-1 levels, and H 2 O 2 -induced neuronal apoptosis and autophagy. Taken together, phillyrin alleviates I/R injury by inhibiting neuronal cell apoptosis and autophagy pathway, which may provide a new treatment strategy for cerebral I/R injury.

Sertraline Pre-Treatment Attenuates Hemorrhagic Transformation Induced in Rats after Cerebral Ischemia Reperfusion via Down Regulation of Neuronal CD163: Involvement of M1/M2 Polarization Interchange and Inhibiting Autophagy

“…In addition, Beclin-1 is critically involved in lysosome fusion and autophagy initiation (Wei et al 2021 ). Moreover, many studies noted that autophagic upregulation is accompanied by apoptotic enhancement (Li et al 2015 ; Chen et al 2022 ). In our study, PI3K, mTOR, Beclin-1 and LC3 II/I expression were elevated in the cerebral I/R group, along with increased levels of apoptotic makers, caspase-3, Bax, decrease of Bcl-2 content, as well as downregulation of intact neurons number in both cortex and hippocampal CA1 region.…”

Role of traditional Chinese medicine monomers in cerebral ischemia/reperfusion injury:a review of the mechanism

“…Pre-administration of betulinic acid (50 mg/kg in vivo ) could increase the expression of SIRT1, reduce the acetylation of FOXO1, and thus reduce the expression of autophagy protein ( Zhao et al, 2021 ). Phillyrin (100 mg/kg in vivo , 80 μm in vitro ) could reduce the expression of autophagy protein in MCAO/R animal models and H 2 O 2 -induced cell models, thereby reducing CIRI ( Chen et al, 2022a ). Autophagy has also been enhanced through pre-administration of berberine (40 mg/kg in vivo , 10 −5 μg/L in vitro ) ( Zhang et al, 2016c ).…”

“…Phillyrin Phillyrin is an important active ingredient extracted from Forsythia suspensa (Thunb.) Vahl, which has anti-inflammatory, antioxidant, and other physiological functions ( Han et al, 2018 ), and could reduce I/R damage by inhibiting neuronal apoptosis and autophagy pathways ( Chen et al, 2022a ).…”

Mechanism of PGC-1α-mediated mitochondrial biogenesis in cerebral ischemia–reperfusion injury

“…Mitochondrial dysfunction also plays an important role in the mechanism of neuronal apoptosis. After CIRI, a large amount of ROS produced by mitochondria can trigger a variety of pathological signaling pathways, such as mitochondria-dependent apoptosis, DNA damage response, and inflammatory response, in addition to directly damaging lipids, proteins and nucleic acids in cells ( Chen et al, 2022 ). Among them, apoptosis can be initiated by damage to mitochondria, followed by induction of cell death through the release of pro-apoptotic proteins such as cytochrome c or apoptosis-inducing factor ( Niizuma et al, 2010 ).…”