Post-Treatment with Erinacine A, a Derived Diterpenoid of H. erinaceus, Attenuates Neurotoxicity in MPTP Model of Parkinson's Disease

被引:33
作者
Lee, Kam-Fai [1 ]
Tung, Shui-Yi [2 ,3 ]
Teng, Chih-Chuan [2 ,4 ]
Shen, Chien-Heng [2 ]
Hsieh, Meng Chiao [5 ,6 ]
Huang, Cheng-Yi [5 ]
Lee, Ko-Chao [7 ,8 ,9 ]
Lee, Li-Ya [10 ]
Chen, Wan-Ping [10 ]
Chen, Chin-Chu [10 ]
Huang, Wen-Shih [3 ,5 ]
Kuo, Hsing-Chun [4 ,5 ,11 ,12 ]
机构
[1] Chang Gung Mem Hosp, Dept Pathol, Chiayi 61363, Taiwan
[2] Chang Gung Mem Hosp, Dept Hepatogastroenterol, Chiayi 61363, Taiwan
[3] Chang Gung Univ, Coll Med, Taoyuan 33302, Taiwan
[4] Chang Gung Univ Sci & Technol, Dept Nursing, Chiayi 61363, Taiwan
[5] Chang Gung Mem Hosp, Div Colon & Rectal Surg, Dept Surg, Chiayi 61363, Taiwan
[6] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan 33302, Taiwan
[7] Chang Gung Univ, Div Colorectal Surg, Dept Surg, Chang Gung Mem Hosp,Kaohsiung Med Ctr,Coll Med, Kaohsiung 83301, Taiwan
[8] Shu Te Univ, Dept Informat Management, Kaohsiung 82445, Taiwan
[9] Shu Te Univ, Coll Liberal Educ, Kaohsiung 82445, Taiwan
[10] Grape King Bio Ltd, Grape King Biotechnol Inc, Taoyuan 32542, Taiwan
[11] Chang Gung Univ Sci & Technol, Res Ctr Ind Human Ecol, Taoyuan 33303, Taiwan
[12] CGUST, Chron Dis & Hlth Promot Res Ctr, Chiayi 61363, Taiwan
关键词
Hericium erinaceus; MPTP; ROS; PAK1; p21; COLORECTAL-CANCER CELLS; HERICIUM-ERINACEUS; ACTIVATION; GROWTH; PAK1; YAMABUSHITAKE; INHIBITION; NUTRITION; PATHOLOGY; CULTURE;
D O I
10.3390/antiox9020137
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hericium erinaceus, a valuable pharmaceutical and edible mushroom, contains potent bioactive compounds such as H. erinaceus 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+)-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+ 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 IRE1 alpha/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.
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页数:17
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