Biomaterial Database

Sappanone A Protects Against Inflammation, Oxidative Stress and Apoptosis in Cerebral Ischemia-Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress. 2021

Meihua Wang, and Zhilin Chen, and Lei Yang, and Lei Ding

Department of Neurosurgery & Neurocritical Care, Huashan Hospital Affiliated to Fudan University, Shanghai, 200040, China.

Endoplasmic reticulum stress is an important contributor to the cerebral ischemic injury. Sappanone A (SA), a kind of natural homoisoflavanone extracted from Caesalpinia sappan L, has been evidenced to exhibit anti-inflammatory and antioxidative properties. The present study aimed to investigate the potential neuroprotective effects of SA in cerebral ischemia-reperfusion injury. The potential neuroprotective effect of SA was tested in a rat model of middle cerebral artery occlusion (MCAO) allowing reperfusion and PC12 cell model of oxygen-glucose deprivation and reperfusion (OGD/R). Post-ischemic neuronal injury was evaluated by 2, 3, 5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining. The levels of inflammatory factors and oxidative stress-related markers were detected using corresponding kits. Cell apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or flow cytometry, and the expression of apoptosis-associated proteins was determined using western blot analysis. Subsequently, endoplasmic reticulum stress-related proteins were detected through western blot analysis, and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) was overexpressed to confirm the contribution of endoplasmic reticulum stress inhibition by SA to the neuroprotective effects post OGD/R. Results revealed that SA was effective in ameliorating cerebral infarction and pathological injuries post-reperfusion following MCAO, which is associated with reduced inflammation, oxidative stress, and cell apoptosis by SA in the brain. Consistently, these neuroprotective effects of SA post ischemia-reperfusion were also observed in a PC12 cell model of OGD/R. Importantly, endoplasmic reticulum stressors, including the CHOP, the 78 kDa glucose-regulated protein 78 (GRP78), and phosphorylated eukaryotic initiation factors 2α (EIF-2α), were significantly downregulated by SA, while CHOP overexpression attenuated the beneficial effects of SA on inflammation, oxidative stress, and apoptosis in OGD/R-induced PC12 cells. These results demonstrated that SA alleviates endoplasmic reticulum stress, ameliorating inflammation, oxidative stress, and apoptosis, and thereby serves as therapeutic potential for protection against cerebral ischemia-reperfusion injury in ischemic stroke.

UI	MeSH Term	Description	Entries
D007529	Isoflavones	3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.	3-Benzylchroman-4-One,3-Benzylidene-4-Chromanone,Homoisoflavone,Homoisoflavones,Isoflavone,Isoflavone Derivative,3-Benzylchroman-4-Ones,3-Benzylidene-4-Chromanones,Isoflavone Derivatives,3 Benzylchroman 4 One,3 Benzylchroman 4 Ones,3 Benzylidene 4 Chromanone,3 Benzylidene 4 Chromanones,Derivative, Isoflavone,Derivatives, Isoflavone
D008297	Male		Males
D009474	Neurons	The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.	Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006360	Heat-Shock Proteins	Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions.	Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000893	Anti-Inflammatory Agents	Substances that reduce or suppress INFLAMMATION.	Anti-Inflammatory Agent,Antiinflammatory Agent,Agents, Anti-Inflammatory,Agents, Antiinflammatory,Anti-Inflammatories,Antiinflammatories,Antiinflammatory Agents,Agent, Anti-Inflammatory,Agent, Antiinflammatory,Agents, Anti Inflammatory,Anti Inflammatories,Anti Inflammatory Agent,Anti Inflammatory Agents
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal