Pretreatment by Evodiamine is Neuroprotective in Cerebral Ischemia: Up-Regulated pAkt, pGSK3β, Down-Regulated NF-κB Expression, and Ameliorated BBB Permeability

Abstract

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Evodiamine (Evo) has been proved to elicit a variety of biological effects through its anti-inflammatory property in the treatment of infectious disease, Alzheimer's disease and hypoxia-induced inflammatory response. Whether this protective effect applies to cerebral ischemic injury, we therefore investigated the potential neuroprotective role of Evo and the underlying mechanisms. Male Institute of Cancer Research (ICR) mice were subjected to permanent middle cerebral artery occlusion (pMCAO) and randomly divided into five groups: Sham (sham-operated + 1% DMSO + 0.5% tween80), pMCAO (pMCAO + 0.9% saline), Vehicle (pMCAO + 1% DMSO + 0.5% tween80), Evo-L (Vehicle + Evo 50 mg/kg) and Evo-H (Vehicle + Evo 100 mg/kg) groups. Evo was administered intragastrically twice daily for 3 days, and once again 30 min before mouse brain ischemia was induced by pMCAO. Neurological deficit, brain water content and infarct size were measured at 24 h after stroke. The expression of pAkt, pGSK3β, NF-κB and claudin-5 in ischemic cerebral cortex was analyzed by western blot and qRT-PCR. Compared with Vehicle group, Evo significantly ameliorated neurological deficit, brain water content and infarct size, upregulated the expression of pAkt, pGSK3β and claudin-5, and downregulated the nuclear accumulation of NF-κB (P < 0.05). Evo protected the brain from ischemic damage caused by pMCAO; this effect may be through upregulation of pAkt, pGSK3β and claudin-5, and downregulation of NF-κB expression.

Evodiamine Prevents Isoproterenol-Induced Cardiac Fibrosis by Regulating Endothelial-to-Mesenchymal Transition

“…The animals were allowed free access to a standard commercial diet and tap water. The mice were randomly divided into 4 groups (20 per group) for treatment: control, cardiac fibrosis (ISO), and low-and high-dose evodiamine (50 and 100 mg/kg/day, respectively) [37,38]. For the ISO model, ISO (Sigma-Aldrich Co.) was injected subcutaneously in mice at 10 mg/kg/day for 3 days and 5 mg/kg/day for 11 days.…”

Radiosynthesis and in Vivo Evaluation of [11C]A1070722, a High Affinity GSK-3 PET Tracer in Primate Brain

“…10–14 More recent studies suggest the modulation of GSK-3 in either the direct or downstream mechanism of action of mood stabilizers, antidepressants, and anti-inflammatory medications currently in use. 15–18 Small molecule inhibitors of GSK-3 are currently under development for a broad range of central nervous system (CNS) disorders including bipolar disorder, depression, diabetes, schizophrenia, and Alzheimer’s disease. 19–22 Biological imaging of GSK-3 expression with radiolabeled small molecule inhibitors may offer a direct and more sensitive approach to monitor the clinical potential of targeted therapeutics and treatments.…”

Evodiamine inhibits RANKL‐induced osteoclastogenesis and prevents ovariectomy‐induced bone loss in mice

“…A previous study reported that EVO significantly suppresses zymosan‐induced inflammation by inhibiting the NF‐κB signalling pathway in the murine RAW264.7 macrophage cell line . EVO also exerts neuroprotective effects via down‐regulated NF‐κB expression to protect against permanent middle cerebral artery occlusion‐induced brain injury in mice . However, the effect of EVO on osteoclastogenesis remains unknown.…”