Therapeutic Effects of Decursin and Angelica gigas Nakai Root Extract in Gerbil Brain after Transient Ischemia via Protecting BBB Leakage and Astrocyte Endfeet Damage

Abstract

Angelica gigas Nakai root contains decursin which exerts beneficial properties such as anti-amnesic and anti-inflammatory activities. Until now, however, the neuroprotective effects of decursin against transient ischemic injury in the forebrain have been insufficiently investigated. Here, we revealed that post-treatment with decursin and the root extract saved pyramidal neurons in the hippocampus following transient ischemia for 5 min in gerbil forebrain. Through high-performance liquid chromatography, we defined that decursin was contained in the extract as 7.3 ± 0.2%. Based on this, we post-treated with 350 mg/kg of extract, which is the corresponding dosage of 25 mg/kg of decursin that exerted neuroprotection in gerbil hippocampus against the ischemia. In addition, behavioral tests were conducted to evaluate ischemia-induced dysfunctions via tests of spatial memory (by the 8-arm radial maze test) and learning memory (by the passive avoidance test), and post-treatment with the extract and decursin attenuated ischemia-induced memory impairments. Furthermore, we carried out histochemistry, immunohistochemistry, and double immunohistofluorescence. Pyramidal neurons located in the subfield cornu ammonis 1 (CA1) among the hippocampal subfields were dead at 5 days after the ischemia; however, treatment with the extract and decursin saved the pyramidal neurons after ischemia. Immunoglobulin G (IgG, an indicator of extravasation), which is not found in the parenchyma in normal brain tissue, was apparently shown in CA1 parenchyma from 2 days after the ischemia, but IgG leakage was dramatically attenuated in the CA1 parenchyma treated with the extract and decursin. Furthermore, astrocyte endfeet, which are a component of the blood–brain barrier (BBB), were severely damaged at 5 days after the ischemia; however, post-treatment with the extract and decursin dramatically attenuated the damage of the endfeet. In brief, therapeutic treatment of the extract of Angelica gigas Nakai root and decursin after 5 min transient forebrain ischemia protected hippocampal neurons from the ischemia, showing that ischemia-induced BBB leakage and damage of astrocyte endfeet was significantly attenuated by the extract and decursin. Based on these findings, we suggest that Angelica gigas Nakai root containing decursin can be employed as a pharmaceutical composition to develop a therapeutic strategy for brain ischemic injury.

Populus tomentiglandulosa Extract Is Rich in Polyphenols and Protects Neurons, Astrocytes, and the Blood-Brain Barrier in Gerbil Striatum Following Ischemia-Reperfusion Injury

“…For reference on AEF, the AEF of astrocytes envelop almost all (>99%) of the endothelium [ 64 ]. It has been reported that, in a gerbil model of tFI, microvessels enclosed by AEF are significantly reduced in the hippocampal CA1 region after 5-min tFI [ 65 ]. Taken together, our findings suggest that the increase in GFAP immunoreactivity in astrocytes in the ischemic striatum is related with an uptake of harmful substances following tFI injury and that this astrogliosis is attenuated or protected by PTE, which may be associated with neuroprotection.…”

Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus

“…TFI was induced in accordance with a previously published method [ 4 , 12 ]. In brief, the gerbils were anesthetized by inhaling 2.5% isoflurane (Hana Pharm.…”

“…To evaluate short term memory following TFI, PAT was conducted in the light of previous studies [ 12 , 22 ]. In short, we used the Gemini Avoidance System (GEM 392) (San Diego Instruments, San Diego, CA, USA) which consists of dark and light sections communicating by a vertical sliding door between the two sections.…”

“…8-ARMT was performed in order to evaluate spatial memory following TFI in accordance with previously described methods [ 4 , 11 , 12 ]. Briefly, a central platform consisting of a non-transparent acryl board (diameter, 20 cm) with radially extended eight arms (width, 5 cm; height, 9 cm; length, 35 cm) (Stoelting Co., Wood Dale, IL, USA) was used.…”

“…In addition to delayed neuronal death, it has been demonstrated that TFI can cause the damage of blood-brain barrier (BBB) integrity, leading to leakage and increased permeability (i.e., vasogenic edema, abnormal exchange of molecules, etc.) [ 9 - 12 ].…”