<i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation

Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether <i>...

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Main Authors: Hyun-Bae Kang, Shin-Hye Kim, Sun-Ho Uhm, Do-Kyung Kim, Nam-Seob Lee, Young-Gil Jeong, Nak-Yun Sung, Dong-Sub Kim, In-Jun Han, Young-Choon Yoo, Seung-Yun Han
Format: Article
Language:English
Published: MDPI AG 2022-01-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/44/1/19
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author Hyun-Bae Kang
Shin-Hye Kim
Sun-Ho Uhm
Do-Kyung Kim
Nam-Seob Lee
Young-Gil Jeong
Nak-Yun Sung
Dong-Sub Kim
In-Jun Han
Young-Choon Yoo
Seung-Yun Han
author_facet Hyun-Bae Kang
Shin-Hye Kim
Sun-Ho Uhm
Do-Kyung Kim
Nam-Seob Lee
Young-Gil Jeong
Nak-Yun Sung
Dong-Sub Kim
In-Jun Han
Young-Choon Yoo
Seung-Yun Han
author_sort Hyun-Bae Kang
collection DOAJ
description Vascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether <i>Perilla frutescens</i> leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.
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spelling doaj.art-0963b96860c24399929482b798695a1d2023-11-23T13:22:35ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-01-0144125727210.3390/cimb44010019<i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial ActivationHyun-Bae Kang0Shin-Hye Kim1Sun-Ho Uhm2Do-Kyung Kim3Nam-Seob Lee4Young-Gil Jeong5Nak-Yun Sung6Dong-Sub Kim7In-Jun Han8Young-Choon Yoo9Seung-Yun Han10Department of Anatomy, College of Medicine, Konyang University, Daejeon 35365, KoreaDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, KoreaDepartment of Anatomy, College of Medicine, Konyang University, Daejeon 35365, KoreaDepartment of Anatomy, College of Medicine, Konyang University, Daejeon 35365, KoreaDepartment of Anatomy, College of Medicine, Konyang University, Daejeon 35365, KoreaDepartment of Anatomy, College of Medicine, Konyang University, Daejeon 35365, KoreaDivision of Natural Product Research, Korea Prime Pharmacy Co., Ltd., Jeonnam 58144, KoreaDivision of Natural Product Research, Korea Prime Pharmacy Co., Ltd., Jeonnam 58144, KoreaDivision of Natural Product Research, Korea Prime Pharmacy Co., Ltd., Jeonnam 58144, KoreaDepartment of Microbiology, College of Medicine, Konyang University, Daejeon 35365, KoreaDepartment of Anatomy, College of Medicine, Konyang University, Daejeon 35365, KoreaVascular dementia (VaD) is characterized by a time-dependent memory deficit and essentially combined with evidence of neuroinflammation. Thus, polyphenol-rich natural plants, which possess anti-inflammatory properties, have received much scientific attention. This study investigated whether <i>Perilla frutescens</i> leaf extract (PFL) exerts therapeutic efficacy against VaD. Sprague Dawley rats were divided into five groups: SO, sham-operated and vehicle treatment; OP, operated and vehicle treatment; PFL-L, operated and low-dose (30 mg/kg) PFL treatment; PFL-M, operated and medium-dose (60 mg/kg) PFL treatment; and PFL-H, operated and high-dose (90 mg/kg) PFL treatment. Two-vessel occlusion and hypovolemia (2VO/H) were employed as a surgical model of VaD, and PFL was given orally perioperatively for 23 days. The rats underwent the Y-maze, Barnes maze, and passive avoidance tests and their brains were subjected to histologic studies. The OP group showed VaD-associated memory deficits, hippocampal neuronal death, and microglial activation; however, the PFL-treated groups showed significant attenuations in all of the above parameters. Using lipopolysaccharide (LPS)-stimulated BV-2 cells, a murine microglial cell line, we measured PFL-mediated changes on the production of nitric oxide (NO), TNF-α, and IL-6, and the activities of their upstream MAP kinases (MAPKs)/NFκB/inducible NO synthase (iNOS). The LPS-induced upregulations of NO, TNF-α, and IL-6 production and MAPKs/NFκB/iNOS activities were globally and significantly reversed by 12-h pretreatment of PFL. This suggests that PFL can counteract VaD-associated structural and functional deterioration through the attenuation of neuroinflammation.https://www.mdpi.com/1467-3045/44/1/19<i>Perilla frutescens</i>vascular dementiahippocampal neuronneuroinflammation
spellingShingle Hyun-Bae Kang
Shin-Hye Kim
Sun-Ho Uhm
Do-Kyung Kim
Nam-Seob Lee
Young-Gil Jeong
Nak-Yun Sung
Dong-Sub Kim
In-Jun Han
Young-Choon Yoo
Seung-Yun Han
<i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation
Current Issues in Molecular Biology
<i>Perilla frutescens</i>
vascular dementia
hippocampal neuron
neuroinflammation
title <i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation
title_full <i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation
title_fullStr <i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation
title_full_unstemmed <i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation
title_short <i>Perilla frutescens</i> Leaf Extract Attenuates Vascular Dementia-Associated Memory Deficits, Neuronal Damages, and Microglial Activation
title_sort i perilla frutescens i leaf extract attenuates vascular dementia associated memory deficits neuronal damages and microglial activation
topic <i>Perilla frutescens</i>
vascular dementia
hippocampal neuron
neuroinflammation
url https://www.mdpi.com/1467-3045/44/1/19
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