Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease
<i>Hericium erinaceus</i>, a valuable pharmaceutical and edible mushroom, contains potent bioactive compounds such as <i>H. erinaceus</i> mycelium (HEM) and its derived ethanol extraction of erinacine A, which have been found to regulate physiological functions in our previou...
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| Format: | Article |
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MDPI AG
2020-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/2/137 |
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| author | Kam-Fai Lee Shui-Yi Tung Chih-Chuan Teng Chien-Heng Shen Meng Chiao Hsieh Cheng-Yi Huang Ko-Chao Lee Li-Ya Lee Wan-Ping Chen Chin-Chu Chen Wen-Shih Huang Hsing-Chun Kuo |
| author_facet | Kam-Fai Lee Shui-Yi Tung Chih-Chuan Teng Chien-Heng Shen Meng Chiao Hsieh Cheng-Yi Huang Ko-Chao Lee Li-Ya Lee Wan-Ping Chen Chin-Chu Chen Wen-Shih Huang Hsing-Chun Kuo |
| author_sort | Kam-Fai Lee |
| collection | DOAJ |
| description | <i>Hericium erinaceus</i>, a valuable pharmaceutical and edible mushroom, contains potent bioactive compounds such as <i>H. erinaceus</i> mycelium (HEM) and its derived ethanol extraction of erinacine A, which have been found to regulate physiological functions in our previous study. However, HEM or erinacine A with post-treatment regimens also shows effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, but its mechanisms remain unknown. By using annexin-V−fluorescein-isothiocyanate (FITC)/propidium iodide staining and a 2’,7’ −dichlorofluorescin diacetate (DCFDA) staining assay, the cell death, cell viability, and reactive oxygen species (ROS) of 1-methyl-4-phenylpyridinium (MMP<sup>+</sup>)-treated Neuro-2a (N2a) cells with or without erinacine A addition were measured, respectively. Furthermore, signaling molecules for regulating the p21/GADD45 cell death pathways and PAKalpha, p21 (RAC1) activated kinase 1 (PAK1) survival pathways were also detected in the cells treated with MPP<sup>+</sup> and erinacine A by Western blots. In neurotoxic animal models of MPTP induction, the effects of HEM or erinacine A and its mechanism in vivo were determined by measuring the TH-positive cell numbers and the protein level of the substantia nigra through a brain histological examination. Our results demonstrated that post-treatment with erinacine A was capable of preventing the cytotoxicity of neuronal cells and the production of ROS in vitro and in vivo through the neuroprotective mechanism for erinacine A to rescue the neurotoxicity through the disruption of the IRE1α/TRAF2 interaction and the reduction of p21 and GADD45 expression. In addition, erinacine A treatment activated the conserved signaling pathways for neuronal survival via the phosphorylation of PAK1, AKT, LIM domain kinase 2 (LIMK2), extracellular signal-regulated kinases (ERK), and Cofilin. Similar changes in the signal molecules also were found in the substantia nigra of the MPTP, which caused TH+ neuron damage after being treated with erinacine A in the post-treatment regimens in a dose-dependent manner. Taken together, our data indicated a novel mechanism for post-treatment with erinacine A to protect from neurotoxicity through regulating neuronal survival and cell death pathways. |
| first_indexed | 2024-03-12T06:00:11Z |
| format | Article |
| id | doaj.art-03a6b7240c634d04954b3c4b7264a3a8 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-12T06:00:11Z |
| publishDate | 2020-02-01 |
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| series | Antioxidants |
| spelling | doaj.art-03a6b7240c634d04954b3c4b7264a3a82023-09-03T04:10:46ZengMDPI AGAntioxidants2076-39212020-02-019213710.3390/antiox9020137antiox9020137Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s DiseaseKam-Fai Lee0Shui-Yi Tung1Chih-Chuan Teng2Chien-Heng Shen3Meng Chiao Hsieh4Cheng-Yi Huang5Ko-Chao Lee6Li-Ya Lee7Wan-Ping Chen8Chin-Chu Chen9Wen-Shih Huang10Hsing-Chun Kuo11Department of Pathology, Chang Gung Memorial Hospital, Chiayi 61363, TaiwanDepartment of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi 61363, TaiwanDepartment of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi 61363, TaiwanDepartment of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Chiayi 61363, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 61363, TaiwanDivision of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 61363, TaiwanDivision of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 83301 TaiwanGrape King Biotechnology Inc (Grape King Bio Ltd.), Zhong-Li, Taoyuan 32542, TaiwanGrape King Biotechnology Inc (Grape King Bio Ltd.), Zhong-Li, Taoyuan 32542, TaiwanGrape King Biotechnology Inc (Grape King Bio Ltd.), Zhong-Li, Taoyuan 32542, TaiwanCollege of Medicine, Chang Gung University, Taoyuan 33302, TaiwanDepartment of Nursing, Chang Gung University of Science and Technology, Chiayi 61363, Taiwan<i>Hericium erinaceus</i>, a valuable pharmaceutical and edible mushroom, contains potent bioactive compounds such as <i>H. erinaceus</i> mycelium (HEM) and its derived ethanol extraction of erinacine A, which have been found to regulate physiological functions in our previous study. However, HEM or erinacine A with post-treatment regimens also shows effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, but its mechanisms remain unknown. By using annexin-V−fluorescein-isothiocyanate (FITC)/propidium iodide staining and a 2’,7’ −dichlorofluorescin diacetate (DCFDA) staining assay, the cell death, cell viability, and reactive oxygen species (ROS) of 1-methyl-4-phenylpyridinium (MMP<sup>+</sup>)-treated Neuro-2a (N2a) cells with or without erinacine A addition were measured, respectively. Furthermore, signaling molecules for regulating the p21/GADD45 cell death pathways and PAKalpha, p21 (RAC1) activated kinase 1 (PAK1) survival pathways were also detected in the cells treated with MPP<sup>+</sup> and erinacine A by Western blots. In neurotoxic animal models of MPTP induction, the effects of HEM or erinacine A and its mechanism in vivo were determined by measuring the TH-positive cell numbers and the protein level of the substantia nigra through a brain histological examination. Our results demonstrated that post-treatment with erinacine A was capable of preventing the cytotoxicity of neuronal cells and the production of ROS in vitro and in vivo through the neuroprotective mechanism for erinacine A to rescue the neurotoxicity through the disruption of the IRE1α/TRAF2 interaction and the reduction of p21 and GADD45 expression. In addition, erinacine A treatment activated the conserved signaling pathways for neuronal survival via the phosphorylation of PAK1, AKT, LIM domain kinase 2 (LIMK2), extracellular signal-regulated kinases (ERK), and Cofilin. Similar changes in the signal molecules also were found in the substantia nigra of the MPTP, which caused TH+ neuron damage after being treated with erinacine A in the post-treatment regimens in a dose-dependent manner. Taken together, our data indicated a novel mechanism for post-treatment with erinacine A to protect from neurotoxicity through regulating neuronal survival and cell death pathways.https://www.mdpi.com/2076-3921/9/2/137<i>hericium erinaceus</i>mptprospak1p21 |
| spellingShingle | Kam-Fai Lee Shui-Yi Tung Chih-Chuan Teng Chien-Heng Shen Meng Chiao Hsieh Cheng-Yi Huang Ko-Chao Lee Li-Ya Lee Wan-Ping Chen Chin-Chu Chen Wen-Shih Huang Hsing-Chun Kuo Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease Antioxidants <i>hericium erinaceus</i> mptp ros pak1 p21 |
| title | Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease |
| title_full | Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease |
| title_fullStr | Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease |
| title_full_unstemmed | Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease |
| title_short | Post-Treatment with Erinacine A, a Derived Diterpenoid of <i>H. erinaceus</i>, Attenuates Neurotoxicity in MPTP Model of Parkinson’s Disease |
| title_sort | post treatment with erinacine a a derived diterpenoid of i h erinaceus i attenuates neurotoxicity in mptp model of parkinson s disease |
| topic | <i>hericium erinaceus</i> mptp ros pak1 p21 |
| url | https://www.mdpi.com/2076-3921/9/2/137 |
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