The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism

Abstract

Background: Caesalpinia sappan L. (C. sappan) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored.Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R).Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 μg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress.Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.

Sappanone A alleviates hypoxia/reoxygenation-induced cardiomyocytes injury through inhibition of mitochondrial apoptosis and activation of PI3K–Akt–Gsk-3β pathway

“…The dried heartwood of Caesalpinia sappan L. is a traditional herb that could be used to accelerate blood circulation and remove blood stasis [11]. Recent studies have reported that the ethanolic extract of Caesalpinia sappan L. heartwood could protect HEI-OC1 cells against tert-butylhydroperoxide (t-BHP)-induced oxidative injury [12] and prevent cerebral ischemia reperfusion injury in a rat model [13]. SA is an active constituent isolated from Caesalpinia sappan L. heartwood and exhibits antioxidant, anti-inflammatory and anti-apoptotic activities.…”

Pycnogenol® Supplementation Attenuates Memory Deficits and Protects Hippocampal CA1 Pyramidal Neurons via Antioxidative Role in a Gerbil Model of Transient Forebrain Ischemia

“…Historically, medicinal plants have been proven their value as therapeutic sources for neurological disorders, including cerebral ischemia (ischemic stroke) [ 34 , 35 , 36 ]. In our current study, we evaluated the neuroprotective effects of pretreated PYC originating from the maritime pine bark in the CA1 area of gerbil hippocampus following TFI using histochemistry with CV, immunohistochemistry with NeuN, and histofluorescence with F-J B.…”

<p>Sappanone A Protects Against Myocardial Ischemia Reperfusion Injury by Modulation of Nrf2</p>

“…22 Notably, the ethanolic extract of Caesalpinia sappan L. heartwood has been reported to protect the brain against ischemia reperfusion injury in a middle cerebral artery occlusion (MCAO) rat model. 23 However, it is not clear exactly which ingredient plays an anti-ischemia role. These results suggested that SA is a major ingredient of Caesalpinia sappan L. that accounts for the anti-ischemia effect.…”