Angelica sinensis Exerts Angiogenic and Anti-apoptotic Effects Against Cerebral Ischemia–Reperfusion Injury by Activating p38MAPK/HIF-1α/VEGF-A Signaling in Rats

Abstract

This study evaluated the effects of Angelica sinensis extract [Dang Gui (DG)] administered before 60[Formula: see text]min of middle cerebral artery occlusion followed by 3[Formula: see text]d of reperfusion and investigated the involvement of mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor (HIF)-1[Formula: see text] signaling in the cortical ischemic penumbra. DG was intraperitoneally administered at a dose of 0.25[Formula: see text]g/kg (DG-0.25g), 0.5[Formula: see text]g/kg (DG-0.5g), or 1[Formula: see text]g/kg (DG-1g) 30[Formula: see text]min before the onset of cerebral ischemia. Our study results revealed that DG-0.5g and DG-1g pretreatment effectively attenuated cerebral infarct and improved neurological deficits. DG-0.5g and DG-1g pretreatment significantly downregulated glial fibrillary acidic protein (GFAP), cytochrome c, and cleaved caspase-3 expression and upregulated phospho-p38 MAPK (p-p38 MAPK)/p38 MAPK, phospho-cAMP response element-binding protein (p-CREB)/CREB, cytosolic and mitochondrial phospho-Bad (p-Bad)/Bad ratios, and HIF-1[Formula: see text], vascular endothelial growth factor-A (VEGF-A), phospho-90 kDa ribosomal S6 kinase (p-p90RSK), and von Willebrand factor (vWF) expression in the cortical ischemic penumbra. Pretreatment with SB203580, a p38 MAPK inhibitor, dramatically abrogated the upregulating effects of DG-1g on p-p38 MAPK/p38 MAPK, p-CREB/CREB, and p-Bad/Bad ratios and HIF-1[Formula: see text], VEGF-A, and vWF expression and the downregulating effects of DG-1g on GFAP, cytochrome c, cleaved caspase-3, and cerebral infarction. DG-0.5g and DG-1g pretreatment provided neuroprotective effects against astrocyte-mediated cerebral infarction by activating angiogenic and anti-apoptotic signaling. Moreover, the angiogenic and anti-apoptotic effects of DG pretreatment can be attributed to the activation of p38 MAPK/HIF-1[Formula: see text]/VEGF-A/vWF signaling and p38 MAPK/HIF-1[Formula: see text]/VEGF-A/p-Bad-related regulation of cytochrome c/caspase-3 signaling, respectively, in the cortical ischemic penumbra 3[Formula: see text]d after reperfusion.

RETRACTED: Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

“…Stroke is accepted as the second leading cause of death in adults worldwide, which is characterized by cerebral ischemia because of disturbances for cerebral blood flow caused by thrombi or emboli. 1 - 3 Despite advances in the treatment technique, the prognosis of stroke remains poor. Till date, very limited medications such as tissue plasminogen activator are used to treat ischemic stroke.…”

“… 7 - 11 Ischemia/reperfusion causes the damage of blood–brain barrier (BBB) and neurons and releases various ions, chemicals, growth factors, and neurotransmitters, which further affect the BBB permeability and aggravate the neuronal damage during cerebra ischemia. 3 , 12 , 13 Among the efforts that have been made to attenuate the I/R injury, numerous types of pretreatment measurements have been suggested by accumulating studies. 14 , 15 …”

WITHDRAWN: Angelica Sinensis Extract Protects Against Memory Deficits by Promoting P38 MAPK–mediated Hippocampal Neurogenesis and Neuronal Survival in the Chronic Phase of Transient Global Cerebral Ischemia in Rats

“…The brain tissue sections were prepared, and subsequent immunohistochemistry (IHC) evaluations were performed as previously described [32]. Anti-ki67 antibody used in the IHC evaluation was listed in Table 1.…”

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

“…Hurley et al [22] showed that JH also resulted in a dose-dependent increase in hippocampal BDNF and protected the brain nerves. Cheng et al [23] found that DG pretreatment protected patients from cerebral infarct and improved neurological damage by downregulating the caspase3 and upregulated p-p38 MAPK, hypoxia-inducible factor (HIF-1), vascular endothelial growth factor-A (VEGF-A). Chen et al [24] found that a Danggui Sini decoction could ebe effectively used to protect microvascular endothelial cells of islet microvasculature via PI3K/Akt/iNOS pathway.…”