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

• Main Authors: Kam-Fai Lee (Author), Shui-Yi Tung (Author), Chih-Chuan Teng (Author), Chien-Heng Shen (Author), Meng Chiao Hsieh (Author), Cheng-Yi Huang (Author), Ko-Chao Lee (Author), Li-Ya Lee (Author), Wan-Ping Chen (Author), Chin-Chu Chen (Author), Wen-Shih Huang (Author), Hsing-Chun Kuo (Author)
• Format: Book
• Published: MDPI AG, 2020-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<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&#8722;fluorescein-isothiocyanate (FITC)/propidium iodide staining and a 2&#8217;,7&#8217; &#8722;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&#945;/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.

Item Description

2076-3921
10.3390/antiox9020137