The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways

<i>Hericium erinaceus</i>, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortic...

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Main Authors: Kam-Fai Lee, Yung-Yu Hsieh, Shui-Yi Tung, Chih-Chuan Teng, Kung-Chuan Cheng, Meng-Chiao Hsieh, Cheng-Yi Huang, Ko-Chao Lee, Li-Ya Lee, Wan-Ping Chen, Chin-Chu Chen, Hsing-Chun Kuo
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/13/3/371
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author Kam-Fai Lee
Yung-Yu Hsieh
Shui-Yi Tung
Chih-Chuan Teng
Kung-Chuan Cheng
Meng-Chiao Hsieh
Cheng-Yi Huang
Ko-Chao Lee
Li-Ya Lee
Wan-Ping Chen
Chin-Chu Chen
Hsing-Chun Kuo
author_facet Kam-Fai Lee
Yung-Yu Hsieh
Shui-Yi Tung
Chih-Chuan Teng
Kung-Chuan Cheng
Meng-Chiao Hsieh
Cheng-Yi Huang
Ko-Chao Lee
Li-Ya Lee
Wan-Ping Chen
Chin-Chu Chen
Hsing-Chun Kuo
author_sort Kam-Fai Lee
collection DOAJ
description <i>Hericium erinaceus</i>, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of <i>H. erinaceus</i> mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing <i>H. erinaceus</i> mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of <i>H. erinaceus</i> mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with <i>H. erinaceus</i> mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of <i>H. erinaceus</i> mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.
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spelling doaj.art-ccb3389c16aa4593a3f1390664f0f2312024-03-27T13:18:43ZengMDPI AGAntioxidants2076-39212024-03-0113337110.3390/antiox13030371The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent PathwaysKam-Fai Lee0Yung-Yu Hsieh1Shui-Yi Tung2Chih-Chuan Teng3Kung-Chuan Cheng4Meng-Chiao Hsieh5Cheng-Yi Huang6Ko-Chao Lee7Li-Ya Lee8Wan-Ping Chen9Chin-Chu Chen10Hsing-Chun Kuo11Department of Pathology, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDepartment of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi 613016, TaiwanDivision of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung 833401, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, TaiwanDivision of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung 833401, TaiwanBiotech Research Institute, Grape King Bio Ltd., Taoyuan 325002, TaiwanBiotech Research Institute, Grape King Bio Ltd., Taoyuan 325002, TaiwanBiotech Research Institute, Grape King Bio Ltd., Taoyuan 325002, TaiwanDepartment of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan<i>Hericium erinaceus</i>, a consumable mushroom, has shown a potential to enhance the production of neuroprotective bioactive metabolites. Traumatic brain injury (TBI) often leads to cognitive, physical, and psychosocial impairments, resulting in neuroinflammation and the loss of cortical neurons. In this research, the effects of <i>H. erinaceus</i> mycelium, its derivative erinacine C, along with the underlying mechanisms, were examined in terms of oxidative stress modulation and neurological improvement in a rat model of mild traumatic brain injury (mTBI). Male Sprague-Dawley rats were administered diets containing <i>H. erinaceus</i> mycelium and erinacine C following experimental brain injury; these supplements were continued throughout the recovery phase. The binding activity of NF-E2-related factor 2 (Nrf2) near antioxidant genes in mixed glial cells was measured by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). The motor beam walking test revealed that dietary supplementation of <i>H. erinaceus</i> mycelium resulted in modest improvements in spatial memory while inhibiting neuron cell death and microglial activation according to brain histological examination. These findings were further corroborated by the upregulation of several antioxidant enzymes (catalase, glutathione reductase, thioredoxin reductase, and superoxide dismutase) and phospho-CAMP-response element-binding (p-CREB) levels in the mTBI model treated with <i>H. erinaceus</i> mycelium. Erinacine C treatment led to significantly reduced brain inflammation and normalization of mTBI-induced deficits through the modulation of the Nrf2 activation pathway and upregulated expression of numerous Nrf2-binding antioxidant genes such as catalase, thioredoxin reductase, superoxide dismutase, and brain-derived neurotrophic factor. This study demonstrates the potential of <i>H. erinaceus</i> mycelium and erinacine C in facilitating recovery following mTBI, including the prevention of neuronal injury and inactivation of microglia through the Nrf2-mediated antioxidant pathway in vivo.https://www.mdpi.com/2076-3921/13/3/371<i>Hericium erinaceus</i> myceliumerinacine Cmild traumatic brain injuryNrf2-mediated antioxidant pathway
spellingShingle Kam-Fai Lee
Yung-Yu Hsieh
Shui-Yi Tung
Chih-Chuan Teng
Kung-Chuan Cheng
Meng-Chiao Hsieh
Cheng-Yi Huang
Ko-Chao Lee
Li-Ya Lee
Wan-Ping Chen
Chin-Chu Chen
Hsing-Chun Kuo
The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways
Antioxidants
<i>Hericium erinaceus</i> mycelium
erinacine C
mild traumatic brain injury
Nrf2-mediated antioxidant pathway
title The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways
title_full The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways
title_fullStr The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways
title_full_unstemmed The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways
title_short The Cerebral Protective Effect of Novel Erinacines from <i>Hericium erinaceus</i> Mycelium on In Vivo Mild Traumatic Brain Injury Animal Model and Primary Mixed Glial Cells via Nrf2-Dependent Pathways
title_sort cerebral protective effect of novel erinacines from i hericium erinaceus i mycelium on in vivo mild traumatic brain injury animal model and primary mixed glial cells via nrf2 dependent pathways
topic <i>Hericium erinaceus</i> mycelium
erinacine C
mild traumatic brain injury
Nrf2-mediated antioxidant pathway
url https://www.mdpi.com/2076-3921/13/3/371
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