Neuroprotective effect of Angelica gigas root in a mouse model of ischemic brain injury through MAPK signaling pathway r
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Chinese Medicine Open Access
RESEARCH
Neuroprotective effect of Angelica gigas root in a mouse model of ischemic brain injury through MAPK signaling pathway regulation Se‑Eun Lee1†, Jung‑Hoon Kim1†, Chiyeon Lim2 and Suin Cho1*
Abstract Background: The root of Angelica gigas Nakai (Apiaceae) has been traditionally used as an important herbal medi‑ cine to treat blood-deficiency-related disorders in Eastern Asian countries, and recently, it has been recognized as a potential candidate for improving cardiovascular diseases. Methods: In this study, the neuroprotective effect of a methanol extract of A. gigas root (RAGE) was investigated in a mouse stroke model induced by a 90 min transient middle cerebral artery occlusion (tMCAO). Infarction volumes and morphological changes in brain tissues were measured using TTC, cresyl violet, and H&E staining. The neuroprotec‑ tive mechanism of RAGE was elucidated through investigation of protein expression levels using western blotting, IHC, and ELISA assays. The plasma concentrations of decursin, a major compound in RAGE, were measured after oral administration of RAGE to SD rats. Results: The infarction volumes in brain tissues were significantly reduced and the morphological deteriorations in the brain neuron cells were improved in tMCAO mice when pre-treated with RAGE at 1000 mg/(kg bw·d) for two consecutive days. The neuroprotective mechanism of RAGE was confirmed to attenuate ERK-related MAPK signaling pathways in the ipsilateral hippocampus hemisphere in mice. The concentrations of decursin in rat plasma samples showed peak absorption and elimination in vivo after oral administration of RAGE at 100 mg/rat. Conclusion: Mice administered RAGE before the tMCAO operation had less neuronal cell death than those that were not administered RAGE prior to the operation, and this study provides preclinical evidence for use of A. gigas in ischemic stroke. Keywords: Angelica gigas (apiaceae), Ischemic stroke, Infarction, Neuroprotection, Pharmacokinetics Background Acute ischemic cerebral stroke is considered the leading cause of morbidity and mortality in modern society [1–5]. When ischemic stroke occurs, cerebral inflammation and cell death are induced in the ischemic
*Correspondence: [email protected] † Se-Eun Lee and Jung-Hoon Kim contributed equally to this study 1 Department of Korean Medicine, School of Korean Medicine, Yangsan Campus of Pusan National University, Yangsan 50612, Republic of Korea Full list of author information is available at the end of the article
lesions, and inflammatory signals are activated by harmful stimuli such as arterial occlusion [6–9]. Ischemic stroke causes high morbidity and disability, with many patients needing rehabilitation and longterm care resulting in a massive financial burden on healthcare systems [9, 10]. Thrombolytic agents, such as anticoagulant or antiplatelet agents, have been used for the treatment of stroke with some success. However, there are limitations to their use, including side effects such as hemorrhage, and the
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