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

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

doi:10.3390/antiox13030371

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

Antioxidants (Basel). 2024 Mar 19;13(3):371. doi: 10.3390/antiox13030371.

Authors

Kam-Fai Lee¹, Yung-Yu Hsieh^{2

3}, Shui-Yi Tung^{2

3}, Chih-Chuan Teng^{4

5}, Kung-Chuan Cheng⁶, Meng-Chiao Hsieh⁷, Cheng-Yi Huang⁷, Ko-Chao Lee^{6

8}, Li-Ya Lee⁹, Wan-Ping Chen⁹, Chin-Chu Chen⁹, Hsing-Chun Kuo^{4

5

10

11}

Affiliations

¹ Department of Pathology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
² Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
³ College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan.
⁴ Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan.
⁵ Research Fellow, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
⁶ Division of Colorectal Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung 833401, Taiwan.
⁷ Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan.
⁸ College of Medicine, Chang Gung University, Kaohsiung 833401, Taiwan.
⁹ Biotech Research Institute, Grape King Bio Ltd., Taoyuan 325002, Taiwan.
¹⁰ Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333324, Taiwan.
¹¹ Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan.

Abstract

Hericium erinaceus, 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 H. erinaceus 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 H. erinaceus 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 H. erinaceus 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 H. erinaceus 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 H. erinaceus 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.

Keywords: Hericium erinaceus mycelium; Nrf2-mediated antioxidant pathway; erinacine C; mild traumatic brain injury.

Grants and funding

Funding for this study was provided in part by research grants BMRPD42, CLRPG8L0063, CMRPG6K0281, CMRPG6K0282, CMRPG6K0283, CMRPF6J0081, CMRPF6J0082, CMRPF6J0083, CMRPF6N0031 and ZRRPF6N0011 from Chang Gung Memorial Hospital, Chiayi, Taiwan, and Chang Gung University of Science and Technology, Chiayi Campus, Taiwan. This work was supported by research grants MOST 110-2320-B-255 -005 -MY3, the Ministry of Science and Technology, Taiwan.